{
"info": {
"nct_id": "NCT03866382",
"official_title": "A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)",
"inclusion_criteria": "* Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:\n\n * One measurable site of disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1\n * One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI) for the bone-only cohort.\n * Histologically confirmed diagnosis of one of the following metastatic cohorts:\n\n * Small cell/ neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded\n * Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma (Cohort B) - must be pure (per World Health Organization [WHO] definition), (i.e. urothelial carcinoma with glandular differentiation is not considered a pure adenocarcinoma\n * Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)\n * Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly > or equal ~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)\n * Any penile cancer (Cohort E)\n * Sarcomatoid renal cell carcinoma (Cohort F) - Tumor should be predominantly sarcomatoid ~ 50% (including rhabdoid differentiation) is also unclassified renal cell carcinomas (RCCs): all (assuming they are high grade with metastasis) malignant angiomyolipomas are allowed\n * Other miscellaneous histologic variants of the urothelial carcinoma, such as, but not limited to (Cohort G) : Micropapillary (Tumor should show predominantly > or equal 50% micropapillary architecture), giant cell, lipid-rich, clear cell and nested variants (Tumor should predominantly > or equal 50% show these features), large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns will be considered, as well as small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed), Malignant testicular Sertoli or Leydig cell tumors, and papillary and chromophobe RCC\n\n * Note: Translocation positive renal cell carcinoma patients are eligible. However, AREN1721 should be considered before this trial\n * Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly ~ 50% sarcomatoid differentiation\n * Renal medullary carcinoma (Cohort I) - Per World Health Organization (WHO) definition, ideally confirmed with immunostains\n * Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible\n * Renal Collecting Duct Carcinoma (Cohort K) - Per WHO definition (medullary involvement, predominant tubular morphology, desmoplastic stromal reaction, high grade cytology, infiltrative growth pattern, and absence of other renal cell carcinoma subtype or urothelial carcinoma)\n * Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder\n * H&E slides from diagnostic tumor tissue for retrospective central pathology review\n* Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)\n* Age >= 18 years\n* Patients must be able to swallow oral formulation of the tablets\n* Karnofsky performance status >= 80%\n* Absolute neutrophil count (ANC) >= 1,000/mcL\n* Platelet count >= 75,000/mcL\n* Total bilirubin =< 1.5 x upper limit of normal (ULN). For subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =< 3.0 mg/dL\n* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal (ULN) (or =< 5 x ULN for patients with liver metastases or Gilbert's disease)\n* Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 40 mL/min/1.73 m^2 (calculated using the Chronic Kidney Disease Epidemiology [CKD-EPI] equation or Cockcroft-Gault formula) for patients with creatinine levels above institutional normal\n* Hemoglobin >= 9 g/dL (transfusion of packed red blood cells [PRBCs] allowed)\n* Serum albumin >= 3.2 g/dL\n* Lipase and amylase =< 2.0 x ULN and no radiologic (on baseline anatomical imaging) or clinical evidence of pancreatitis\n* Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed\n* No prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors with the exception of patients with \"urothelial carcinoma\" histology (cohorts D, H, J, L)\n* Human immunodeficiency virus (HIV)-positive patients are eligible if on stable dose of highly active antiretroviral therapy (HAART), no clinically significant drug-drug interactions are anticipated with the current HAART regimen, CD4 counts are greater than 350 and viral load is undetectable\n* Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication only and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies etc. are eligible but should be considered for rheumatologic evaluation for the presence of target organ involvement and potential need for systemic treatment\n* Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones or medications (e.g. thyroiditis managed with propylthiouracil [PTU] or methimazole) including physiologic oral corticosteroids are eligible\n* Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess, and gastrointestinal (GI) obstruction, within 12 months are not eligible\n* Women of childbearing potential must have a negative pregnancy test =< 7 days prior to registration\n\n * Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post menopause is defined as amenorrhea >= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason\n* Pregnant women may not participate in this study because with cabozantinib, nivolumab, and ipilimumab have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib, nivolumab, and ipilimumab, breastfeeding should be discontinued if the mother is treated with these agents\n* The patient has received no cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 2 weeks before the first dose of study treatment\n* The patient has received no radiation therapy:\n\n * To the lungs and mediastinum or abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy\n * To brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT), and 2 weeks for stereotactic body radiation therapy (SBRT) before the first dose of study treatment\n * To the abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy\n * To any other site(s) within 2 weeks before the first dose of study treatment\n* The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment\n* The patient has received no prior treatment with a small molecule kinase inhibitor within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment\n* The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment. Subjects receiving gonadotropin-releasing hormone (GnRH) agonists and antagonists are allowed to participate\n* The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment\n* The patient must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies except alopecia, neuropathy and other non-clinically significant adverse events (AEs) defined as lab elevation with no associated symptoms or sequelae\n* The patient may not have active brain metastases or epidural disease. Patients with brain metastases previously treated with whole brain radiation or radiosurgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility\n* No concomitant treatment with warfarin. Aspirin (up to 325 mg/day), thrombin or factor Xa inhibitors, low-dose warfarin (=< 1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted\n* No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort) or strong CYP3A4 inhibitors\n\n * Because the lists of these agents are constantly changing, it is important to regularly consult medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product\n* The patient has not experienced any of the following:\n\n * Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment\n * Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood per day within 1 months before the first dose of study treatment\n * Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment\n* The patient has no tumor invading any major blood vessels\n* The patient has no evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib. Patients with rectal tumor masses are not eligible\n* The patient has no uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\n\n * Cardiovascular disorders including:\n\n * Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening.\n * Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment\n * The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization. Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard\n * Any history of congenital long QT syndrome\n * Any of the following within 6 months before registration of study treatment:\n\n * Unstable angina pectoris\n * Clinically-significant cardiac arrhythmias (patients with atrial fibrillation are eligible)\n * Stroke (including transient ischemic attack [TIA], or other ischemic event)\n * Myocardial infarction\n * Cardiomyopathy\n * No significant gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\n\n * Any of the following that have not resolved within 28 days before the first dose of study treatment:\n\n * Active peptic ulcer disease\n * Acute diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or malabsorption syndrome\n * None of the following within 2 years before the first dose of study treatment:\n\n * Abdominal fistula or genitourinary fistula\n * Gastrointestinal perforation\n * Bowel obstruction or gastric outlet obstruction\n * Intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 2 years before the first dose of study treatment\n * Disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement are not eligible\n * No other clinically significant disorders such as:\n\n * Severe active infection requiring IV systemic treatment within 14 days before the first dose of study treatment\n * Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment\n * History of organ or allogeneic stem cell transplant\n * Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment (for asymptomatic patients with an elevated thyroid-stimulating hormone [TSH], thyroid replacement may be initiated if clinically indicated without delaying the start of study treatment)\n * No history of major surgery as follows:\n\n * Major surgery within 3 months of the first dose of cabozantinib; however, if there were no wound healing complications, patients with rapidly growing aggressive cancers, may start as soon as 6 weeks if wound has completely healed post-surgery\n * Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications excluding core biopsies and mediport placement\n * Complete wound healing from prior surgery must be confirmed before the first dose of cabozantinib irrespective of the time from surgery\n* No history of severe hypersensitivity reaction to any monoclonal antibody\n* No evidence of active malignancy, requiring systemic treatment within 2 years of registration\n* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, ipilimumab or other agents used in study\n* No positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. If HBV sAG is positive, subsequent ribonucleic acid (RNA) polymerase chain reaction (PCR) must be negative\n* No patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include, but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
"exclusion_criteria": "",
"miscellaneous_criteria": ""
},
"inclusion_lines": [
{
"identified_line": {
"line": "* Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:",
"criterions": [
{
"exact_snippets": "Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan.",
"criterion": "metastatic disease",
"requirement": {
"requirement_type": "definition",
"expected_value": "new or progressive lesions on cross-sectional imaging or bone scan"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan.",
"criterion": "metastatic disease",
"requirement": {
"requirement_type": "definition",
"expected_value": "new or progressive lesions on cross-sectional imaging or bone scan"
}
}
]
}
},
{
"identified_line": {
"line": "* One measurable site of disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1",
"criterions": [
{
"exact_snippets": "One measurable site of disease",
"criterion": "measurable site of disease",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "=",
"value": 1,
"unit": "site"
}
}
},
{
"exact_snippets": "as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1",
"criterion": "RECIST v1.1 compliance",
"requirement": {
"requirement_type": "compliance",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "One measurable site of disease",
"criterion": "measurable site of disease",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "=",
"value": 1,
"unit": "site"
}
}
},
{
"exact_snippets": "as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1",
"criterion": "RECIST v1.1 compliance",
"requirement": {
"requirement_type": "compliance",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI) for the bone-only cohort.",
"criterions": [
{
"exact_snippets": "One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI)",
"criterion": "bone lesion",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "=",
"value": 1,
"unit": "lesion"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI)",
"criterion": "bone lesion",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "=",
"value": 1,
"unit": "lesion"
}
}
},
{
"exact_snippets": "One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI)",
"criterion": "imaging modality",
"requirement": {
"requirement_type": "presence",
"expected_value": [
"tec99",
"sodium fluoride [NaF] PET/CT",
"CT",
"MRI"
]
}
}
]
}
},
{
"identified_line": {
"line": "* Histologically confirmed diagnosis of one of the following metastatic cohorts:",
"criterions": [
{
"exact_snippets": "Histologically confirmed diagnosis",
"criterion": "diagnosis confirmation",
"requirement": {
"requirement_type": "method",
"expected_value": "histologically"
}
},
{
"exact_snippets": "metastatic cohorts",
"criterion": "metastatic cohort",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Histologically confirmed diagnosis",
"criterion": "diagnosis confirmation",
"requirement": {
"requirement_type": "method",
"expected_value": "histologically"
}
},
{
"exact_snippets": "metastatic cohorts",
"criterion": "metastatic cohort",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Small cell/ neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded",
"criterions": [
{
"exact_snippets": "Small cell/ neuroendocrine carcinoma of the bladder",
"criterion": "carcinoma type",
"requirement": {
"requirement_type": "presence",
"expected_value": "small cell/neuroendocrine carcinoma of the bladder"
}
},
{
"exact_snippets": "All urothelial carcinomas with any amount of neuroendocrine differentiation",
"criterion": "neuroendocrine differentiation",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded",
"criterion": "metastasis exclusion",
"requirement": {
"requirement_type": "condition",
"expected_value": "clinically exclude metastasis from another site of origin if tumor is purely neuroendocrine"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Small cell/ neuroendocrine carcinoma of the bladder",
"criterion": "carcinoma type",
"requirement": {
"requirement_type": "presence",
"expected_value": "small cell/neuroendocrine carcinoma of the bladder"
}
},
{
"exact_snippets": "All urothelial carcinomas with any amount of neuroendocrine differentiation",
"criterion": "neuroendocrine differentiation",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
{
"and_criteria": [
{
"exact_snippets": "Small cell/ neuroendocrine carcinoma of the bladder",
"criterion": "carcinoma type",
"requirement": {
"requirement_type": "presence",
"expected_value": "small cell/neuroendocrine carcinoma of the bladder"
}
},
{
"exact_snippets": "If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded",
"criterion": "metastasis exclusion",
"requirement": {
"requirement_type": "condition",
"expected_value": "clinically exclude metastasis from another site of origin if tumor is purely neuroendocrine"
}
}
]
}
]
}
]
}
},
{
"identified_line": {
"line": "* Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma (Cohort B) - must be pure (per World Health Organization [WHO] definition), (i.e. urothelial carcinoma with glandular differentiation is not considered a pure adenocarcinoma",
"criterions": [
{
"exact_snippets": "Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma",
"criterion": "adenocarcinoma type",
"requirement": {
"requirement_type": "presence",
"expected_value": [
"adenocarcinoma of the bladder",
"urachal adenocarcinoma",
"bladder/urethra clear cell adenocarcinoma"
]
}
},
{
"exact_snippets": "must be pure (per World Health Organization [WHO] definition)",
"criterion": "adenocarcinoma purity",
"requirement": {
"requirement_type": "purity",
"expected_value": "pure per WHO definition"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"or_criteria": [
{
"exact_snippets": "Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma",
"criterion": "adenocarcinoma type",
"requirement": {
"requirement_type": "presence",
"expected_value": [
"adenocarcinoma of the bladder",
"urachal adenocarcinoma",
"bladder/urethra clear cell adenocarcinoma"
]
}
},
{
"exact_snippets": "Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma",
"criterion": "adenocarcinoma type",
"requirement": {
"requirement_type": "presence",
"expected_value": [
"urachal adenocarcinoma"
]
}
},
{
"exact_snippets": "Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma",
"criterion": "adenocarcinoma type",
"requirement": {
"requirement_type": "presence",
"expected_value": [
"bladder/urethra clear cell adenocarcinoma"
]
}
}
]
},
{
"exact_snippets": "must be pure (per World Health Organization [WHO] definition)",
"criterion": "adenocarcinoma purity",
"requirement": {
"requirement_type": "purity",
"expected_value": "pure per WHO definition"
}
}
]
}
},
{
"identified_line": {
"line": "* Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)",
"criterions": [
{
"exact_snippets": "Squamous cell carcinoma of the bladder (Cohort C)",
"criterion": "squamous cell carcinoma of the bladder",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)",
"criterion": "purity of squamous cell carcinoma",
"requirement": {
"requirement_type": "purity",
"expected_value": "pure"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Squamous cell carcinoma of the bladder (Cohort C)",
"criterion": "squamous cell carcinoma of the bladder",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)",
"criterion": "purity of squamous cell carcinoma",
"requirement": {
"requirement_type": "purity",
"expected_value": "pure"
}
}
]
}
},
{
"identified_line": {
"line": "* Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly > or equal ~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)",
"criterions": [
{
"exact_snippets": "Tumor should show predominantly > or equal ~ 50% plasmacytoid histology",
"criterion": "plasmacytoid histology",
"requirement": {
"requirement_type": "predominance",
"expected_value": {
"operator": ">=",
"value": 50,
"unit": "%"
}
}
},
{
"exact_snippets": "Tumor should show predominantly > or equal ~ 50% plasmacytoid histology",
"criterion": "plasmacytoid histology",
"requirement": {
"requirement_type": "inclusion",
"expected_value": [
"discohesive growth",
"tumors with signet-ring features",
"tumors with rhabdoid features"
]
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Tumor should show predominantly > or equal ~ 50% plasmacytoid histology",
"criterion": "plasmacytoid histology",
"requirement": {
"requirement_type": "predominance",
"expected_value": {
"operator": ">=",
"value": 50,
"unit": "%"
}
}
},
{
"exact_snippets": "Tumor should show predominantly > or equal ~ 50% plasmacytoid histology",
"criterion": "plasmacytoid histology",
"requirement": {
"requirement_type": "inclusion",
"expected_value": [
"discohesive growth",
"tumors with signet-ring features",
"tumors with rhabdoid features"
]
}
}
]
}
]
}
},
{
"identified_line": {
"line": "* Any penile cancer (Cohort E)",
"criterions": [
{
"exact_snippets": "penile cancer",
"criterion": "penile cancer",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "penile cancer",
"criterion": "penile cancer",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Sarcomatoid renal cell carcinoma (Cohort F) - Tumor should be predominantly sarcomatoid ~ 50% (including rhabdoid differentiation) is also unclassified renal cell carcinomas (RCCs): all (assuming they are high grade with metastasis) malignant angiomyolipomas are allowed",
"criterions": [
{
"exact_snippets": "Sarcomatoid renal cell carcinoma (Cohort F)",
"criterion": "sarcomatoid renal cell carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "Tumor should be predominantly sarcomatoid ~ 50%",
"criterion": "sarcomatoid tumor percentage",
"requirement": {
"requirement_type": "percentage",
"expected_value": {
"operator": "=",
"value": 50,
"unit": "%"
}
}
},
{
"exact_snippets": "rhabdoid differentiation",
"criterion": "rhabdoid differentiation",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "unclassified renal cell carcinomas (RCCs)",
"criterion": "unclassified renal cell carcinomas",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "malignant angiomyolipomas are allowed",
"criterion": "malignant angiomyolipomas",
"requirement": {
"requirement_type": "allowance",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Sarcomatoid renal cell carcinoma (Cohort F)",
"criterion": "sarcomatoid renal cell carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "Tumor should be predominantly sarcomatoid ~ 50%",
"criterion": "sarcomatoid tumor percentage",
"requirement": {
"requirement_type": "percentage",
"expected_value": {
"operator": "=",
"value": 50,
"unit": "%"
}
}
},
{
"exact_snippets": "rhabdoid differentiation",
"criterion": "rhabdoid differentiation",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
{
"and_criteria": [
{
"exact_snippets": "unclassified renal cell carcinomas (RCCs)",
"criterion": "unclassified renal cell carcinomas",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
]
},
{
"exact_snippets": "malignant angiomyolipomas are allowed",
"criterion": "malignant angiomyolipomas",
"requirement": {
"requirement_type": "allowance",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Other miscellaneous histologic variants of the urothelial carcinoma, such as, but not limited to (Cohort G) : Micropapillary (Tumor should show predominantly > or equal 50% micropapillary architecture), giant cell, lipid-rich, clear cell and nested variants (Tumor should predominantly > or equal 50% show these features), large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns will be considered, as well as small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed), Malignant testicular Sertoli or Leydig cell tumors, and papillary and chromophobe RCC",
"criterions": [
{
"exact_snippets": "Micropapillary (Tumor should show predominantly > or equal 50% micropapillary architecture)",
"criterion": "micropapillary architecture",
"requirement": {
"requirement_type": "predominance",
"expected_value": {
"operator": ">=",
"value": 50,
"unit": "%"
}
}
},
{
"exact_snippets": "Micropapillary (Tumor should show predominantly > or equal 50% micropapillary architecture)",
"criterion": "micropapillary architecture",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "giant cell",
"criterion": "giant cell variant",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "lipid-rich",
"criterion": "lipid-rich variant",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "clear cell",
"criterion": "clear cell variant",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "nested variants (Tumor should predominantly > or equal 50% show these features)",
"criterion": "nested variant features",
"requirement": {
"requirement_type": "predominance",
"expected_value": {
"operator": ">=",
"value": 50,
"unit": "%"
}
}
},
{
"exact_snippets": "nested variants (Tumor should predominantly > or equal 50% show these features)",
"criterion": "nested variant features",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "large cell neuroendocrine carcinoma",
"criterion": "large cell neuroendocrine carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "lymphoepithelioma-like carcinoma",
"criterion": "lymphoepithelioma-like carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "mixed patterns",
"criterion": "mixed patterns",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed)",
"criterion": "small cell neuroendocrine prostate cancer",
"requirement": {
"requirement_type": "treatment status",
"expected_value": "treatment-naïve"
}
},
{
"exact_snippets": "small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed)",
"criterion": "small cell neuroendocrine prostate cancer",
"requirement": {
"requirement_type": "component amount",
"expected_value": "any amount"
}
},
{
"exact_snippets": "small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed)",
"criterion": "small cell neuroendocrine prostate cancer",
"requirement": {
"requirement_type": "post-treatment status",
"expected_value": false
}
},
{
"exact_snippets": "Malignant testicular Sertoli or Leydig cell tumors",
"criterion": "malignant testicular Sertoli or Leydig cell tumors",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "papillary and chromophobe RCC",
"criterion": "papillary and chromophobe RCC",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Micropapillary (Tumor should show predominantly > or equal 50% micropapillary architecture)",
"criterion": "micropapillary architecture",
"requirement": {
"requirement_type": "predominance",
"expected_value": {
"operator": ">=",
"value": 50,
"unit": "%"
}
}
},
{
"exact_snippets": "Micropapillary (Tumor should show predominantly > or equal 50% micropapillary architecture)",
"criterion": "micropapillary architecture",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
{
"exact_snippets": "giant cell",
"criterion": "giant cell variant",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "lipid-rich",
"criterion": "lipid-rich variant",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "clear cell",
"criterion": "clear cell variant",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"and_criteria": [
{
"exact_snippets": "nested variants (Tumor should predominantly > or equal 50% show these features)",
"criterion": "nested variant features",
"requirement": {
"requirement_type": "predominance",
"expected_value": {
"operator": ">=",
"value": 50,
"unit": "%"
}
}
},
{
"exact_snippets": "nested variants (Tumor should predominantly > or equal 50% show these features)",
"criterion": "nested variant features",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
]
},
{
"exact_snippets": "large cell neuroendocrine carcinoma",
"criterion": "large cell neuroendocrine carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "lymphoepithelioma-like carcinoma",
"criterion": "lymphoepithelioma-like carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "mixed patterns",
"criterion": "mixed patterns",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"and_criteria": [
{
"exact_snippets": "small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed)",
"criterion": "small cell neuroendocrine prostate cancer",
"requirement": {
"requirement_type": "treatment status",
"expected_value": "treatment-naïve"
}
},
{
"exact_snippets": "small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed)",
"criterion": "small cell neuroendocrine prostate cancer",
"requirement": {
"requirement_type": "component amount",
"expected_value": "any amount"
}
},
{
"exact_snippets": "small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed)",
"criterion": "small cell neuroendocrine prostate cancer",
"requirement": {
"requirement_type": "post-treatment status",
"expected_value": false
}
}
]
},
{
"exact_snippets": "Malignant testicular Sertoli or Leydig cell tumors",
"criterion": "malignant testicular Sertoli or Leydig cell tumors",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "papillary and chromophobe RCC",
"criterion": "papillary and chromophobe RCC",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Note: Translocation positive renal cell carcinoma patients are eligible. However, AREN1721 should be considered before this trial",
"criterions": [
{
"exact_snippets": "Translocation positive renal cell carcinoma",
"criterion": "translocation positive renal cell carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"condition": {
"exact_snippets": "Translocation positive renal cell carcinoma",
"criterion": "translocation positive renal cell carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
"then_criteria": null,
"else_criteria": null
}
},
{
"identified_line": {
"line": "* Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly ~ 50% sarcomatoid differentiation",
"criterions": [
{
"exact_snippets": "Sarcomatoid urothelial carcinoma (Cohort H)",
"criterion": "sarcomatoid urothelial carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "Tumor should show predominantly ~ 50% sarcomatoid differentiation",
"criterion": "sarcomatoid differentiation",
"requirement": {
"requirement_type": "percentage",
"expected_value": {
"operator": "=",
"value": 50,
"unit": "%"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Sarcomatoid urothelial carcinoma (Cohort H)",
"criterion": "sarcomatoid urothelial carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "Tumor should show predominantly ~ 50% sarcomatoid differentiation",
"criterion": "sarcomatoid differentiation",
"requirement": {
"requirement_type": "percentage",
"expected_value": {
"operator": "=",
"value": 50,
"unit": "%"
}
}
}
]
}
},
{
"identified_line": {
"line": "* Renal medullary carcinoma (Cohort I) - Per World Health Organization (WHO) definition, ideally confirmed with immunostains",
"criterions": [
{
"exact_snippets": "Renal medullary carcinoma (Cohort I)",
"criterion": "renal medullary carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "Per World Health Organization (WHO) definition",
"criterion": "WHO definition",
"requirement": {
"requirement_type": "adherence",
"expected_value": true
}
},
{
"exact_snippets": "ideally confirmed with immunostains",
"criterion": "confirmation with immunostains",
"requirement": {
"requirement_type": "confirmation",
"expected_value": "ideally"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Renal medullary carcinoma (Cohort I)",
"criterion": "renal medullary carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "Per World Health Organization (WHO) definition",
"criterion": "WHO definition",
"requirement": {
"requirement_type": "adherence",
"expected_value": true
}
}
]
},
{
"exact_snippets": "ideally confirmed with immunostains",
"criterion": "confirmation with immunostains",
"requirement": {
"requirement_type": "confirmation",
"expected_value": "ideally"
}
}
]
}
},
{
"identified_line": {
"line": "* Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible",
"criterions": [
{
"exact_snippets": "Bone-only metastatic GU tumors (non-prostate)",
"criterion": "bone-only metastatic genitourinary tumors",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "All genitourinary histologies, except prostate are eligible",
"criterion": "genitourinary histologies",
"requirement": {
"requirement_type": "exclusion",
"expected_value": "prostate"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Bone-only metastatic GU tumors (non-prostate)",
"criterion": "bone-only metastatic genitourinary tumors",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "All genitourinary histologies, except prostate are eligible",
"criterion": "genitourinary histologies",
"requirement": {
"requirement_type": "exclusion",
"expected_value": "prostate"
}
}
]
}
},
{
"identified_line": {
"line": "* Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder",
"criterions": [
{
"exact_snippets": "Urethra carcinoma (Cohort L)",
"criterion": "urethra carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "May be of any histology",
"criterion": "histology",
"requirement": {
"requirement_type": "type",
"expected_value": "any"
}
},
{
"exact_snippets": "if urothelial carcinoma then must be isolated to the urethra",
"criterion": "urothelial carcinoma location",
"requirement": {
"requirement_type": "location",
"expected_value": "isolated to the urethra"
}
},
{
"exact_snippets": "not have metachronous or synchronous urothelial carcinoma of the bladder",
"criterion": "metachronous or synchronous urothelial carcinoma of the bladder",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"condition": {
"exact_snippets": "Urethra carcinoma (Cohort L)",
"criterion": "urethra carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
"then_criteria": {
"and_criteria": [
{
"exact_snippets": "May be of any histology",
"criterion": "histology",
"requirement": {
"requirement_type": "type",
"expected_value": "any"
}
},
{
"condition": {
"exact_snippets": "if urothelial carcinoma then must be isolated to the urethra",
"criterion": "urothelial carcinoma location",
"requirement": {
"requirement_type": "location",
"expected_value": "isolated to the urethra"
}
},
"then_criteria": {
"exact_snippets": "not have metachronous or synchronous urothelial carcinoma of the bladder",
"criterion": "metachronous or synchronous urothelial carcinoma of the bladder",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
"else_criteria": null
}
]
},
"else_criteria": null
}
},
{
"identified_line": {
"line": "* H&E slides from diagnostic tumor tissue for retrospective central pathology review",
"criterions": [
{
"exact_snippets": "H&E slides from diagnostic tumor tissue",
"criterion": "H&E slides from diagnostic tumor tissue",
"requirement": {
"requirement_type": "availability",
"expected_value": true
}
},
{
"exact_snippets": "retrospective central pathology review",
"criterion": "retrospective central pathology review",
"requirement": {
"requirement_type": "requirement",
"expected_value": "required"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "H&E slides from diagnostic tumor tissue",
"criterion": "H&E slides from diagnostic tumor tissue",
"requirement": {
"requirement_type": "availability",
"expected_value": true
}
},
{
"exact_snippets": "retrospective central pathology review",
"criterion": "retrospective central pathology review",
"requirement": {
"requirement_type": "requirement",
"expected_value": "required"
}
}
]
}
},
{
"identified_line": {
"line": "* Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)",
"criterions": [
{
"exact_snippets": "Patients may have received up to 2 systemic anti-cancer treatments",
"criterion": "systemic anti-cancer treatments",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "<=",
"value": 2,
"unit": "N/A"
}
}
},
{
"exact_snippets": "treatment naive",
"criterion": "treatment naive",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "Patients with small cell carcinoma should have received a platinum-based combination regimen",
"criterion": "small cell carcinoma",
"requirement": {
"requirement_type": "treatment",
"expected_value": "platinum-based combination regimen"
}
},
{
"exact_snippets": "Patients in the bone-only cohort may be urothelial carcinoma histology",
"criterion": "urothelial carcinoma histology",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)",
"criterion": "cisplatin-based chemotherapy",
"requirement": {
"requirement_type": "eligibility",
"expected_value": "cisplatin-eligible"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Patients may have received up to 2 systemic anti-cancer treatments",
"criterion": "systemic anti-cancer treatments",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "<=",
"value": 2,
"unit": "N/A"
}
}
},
{
"exact_snippets": "treatment naive",
"criterion": "treatment naive",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
{
"exact_snippets": "treatment naive",
"criterion": "treatment naive",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
{
"condition": {
"exact_snippets": "Patients with small cell carcinoma should have received a platinum-based combination regimen",
"criterion": "small cell carcinoma",
"requirement": {
"requirement_type": "treatment",
"expected_value": "platinum-based combination regimen"
}
},
"then_criteria": null,
"else_criteria": null
},
{
"condition": {
"exact_snippets": "Patients in the bone-only cohort may be urothelial carcinoma histology",
"criterion": "urothelial carcinoma histology",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
"then_criteria": {
"exact_snippets": "must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)",
"criterion": "cisplatin-based chemotherapy",
"requirement": {
"requirement_type": "eligibility",
"expected_value": "cisplatin-eligible"
}
},
"else_criteria": null
}
]
}
},
{
"identified_line": {
"line": "* Age >= 18 years",
"criterions": [
{
"exact_snippets": "Age >= 18 years",
"criterion": "age",
"requirement": {
"requirement_type": "value",
"expected_value": {
"operator": ">=",
"value": 18,
"unit": "years"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Age >= 18 years",
"criterion": "age",
"requirement": {
"requirement_type": "value",
"expected_value": {
"operator": ">=",
"value": 18,
"unit": "years"
}
}
}
]
}
},
{
"identified_line": {
"line": "* Patients must be able to swallow oral formulation of the tablets",
"criterions": [
{
"exact_snippets": "Patients must be able to swallow oral formulation of the tablets",
"criterion": "ability to swallow",
"requirement": {
"requirement_type": "ability",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Patients must be able to swallow oral formulation of the tablets",
"criterion": "ability to swallow",
"requirement": {
"requirement_type": "ability",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Karnofsky performance status >= 80%",
"criterions": [
{
"exact_snippets": "Karnofsky performance status >= 80%",
"criterion": "Karnofsky performance status",
"requirement": {
"requirement_type": "performance level",
"expected_value": {
"operator": ">=",
"value": 80,
"unit": "%"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Karnofsky performance status >= 80%",
"criterion": "Karnofsky performance status",
"requirement": {
"requirement_type": "performance level",
"expected_value": {
"operator": ">=",
"value": 80,
"unit": "%"
}
}
}
]
}
},
{
"identified_line": {
"line": "* Absolute neutrophil count (ANC) >= 1,000/mcL",
"criterions": [
{
"exact_snippets": "Absolute neutrophil count (ANC) >= 1,000/mcL",
"criterion": "absolute neutrophil count (ANC)",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 1000,
"unit": "mcL"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Absolute neutrophil count (ANC) >= 1,000/mcL",
"criterion": "absolute neutrophil count (ANC)",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 1000,
"unit": "mcL"
}
}
}
]
}
},
{
"identified_line": {
"line": "* Platelet count >= 75,000/mcL",
"criterions": [
{
"exact_snippets": "Platelet count >= 75,000/mcL",
"criterion": "platelet count",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 75000,
"unit": "mcL"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Platelet count >= 75,000/mcL",
"criterion": "platelet count",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 75000,
"unit": "mcL"
}
}
}
]
}
},
{
"identified_line": {
"line": "* Total bilirubin =< 1.5 x upper limit of normal (ULN). For subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =< 3.0 mg/dL",
"criterions": [
{
"exact_snippets": "Total bilirubin =< 1.5 x upper limit of normal (ULN)",
"criterion": "total bilirubin",
"requirement": {
"requirement_type": "level",
"expected_value": {
"operator": "<=",
"value": 1.5,
"unit": "x ULN"
}
}
},
{
"exact_snippets": "subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =< 3.0 mg/dL",
"criterion": "total bilirubin",
"requirement": {
"requirement_type": "level",
"expected_value": {
"operator": "<=",
"value": 3.0,
"unit": "mg/dL"
}
}
}
]
},
"logical_structure": {
"condition": {
"exact_snippets": "subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =< 3.0 mg/dL",
"criterion": "total bilirubin",
"requirement": {
"requirement_type": "level",
"expected_value": "Gilbert's disease or similar syndrome with slow conjugation of bilirubin"
}
},
"then_criteria": {
"exact_snippets": "subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =< 3.0 mg/dL",
"criterion": "total bilirubin",
"requirement": {
"requirement_type": "level",
"expected_value": {
"operator": "<=",
"value": 3.0,
"unit": "mg/dL"
}
}
},
"else_criteria": {
"exact_snippets": "Total bilirubin =< 1.5 x upper limit of normal (ULN)",
"criterion": "total bilirubin",
"requirement": {
"requirement_type": "level",
"expected_value": {
"operator": "<=",
"value": 1.5,
"unit": "x ULN"
}
}
}
}
},
{
"identified_line": {
"line": "* Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 40 mL/min/1.73 m^2 (calculated using the Chronic Kidney Disease Epidemiology [CKD-EPI] equation or Cockcroft-Gault formula) for patients with creatinine levels above institutional normal",
"criterions": [
{
"exact_snippets": "Creatinine =< 1.5 x upper limit of normal (ULN)",
"criterion": "creatinine level",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "<=",
"value": 1.5,
"unit": "x ULN"
}
}
},
{
"exact_snippets": "creatinine clearance >= 40 mL/min/1.73 m^2",
"criterion": "creatinine clearance",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 40,
"unit": "mL/min/1.73 m^2"
}
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Creatinine =< 1.5 x upper limit of normal (ULN)",
"criterion": "creatinine level",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "<=",
"value": 1.5,
"unit": "x ULN"
}
}
}
]
},
{
"and_criteria": [
{
"exact_snippets": "creatinine clearance >= 40 mL/min/1.73 m^2",
"criterion": "creatinine clearance",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 40,
"unit": "mL/min/1.73 m^2"
}
}
}
]
},
{
"condition": {
"exact_snippets": "Creatinine =< 1.5 x upper limit of normal (ULN)",
"criterion": "creatinine level",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "<=",
"value": 1.5,
"unit": "x ULN"
}
}
},
"then_criteria": null,
"else_criteria": {
"exact_snippets": "creatinine clearance >= 40 mL/min/1.73 m^2",
"criterion": "creatinine clearance",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 40,
"unit": "mL/min/1.73 m^2"
}
}
}
}
]
}
},
{
"identified_line": {
"line": "* Hemoglobin >= 9 g/dL (transfusion of packed red blood cells [PRBCs] allowed)",
"criterions": [
{
"exact_snippets": "Hemoglobin >= 9 g/dL",
"criterion": "hemoglobin level",
"requirement": {
"requirement_type": "level",
"expected_value": {
"operator": ">=",
"value": 9,
"unit": "g/dL"
}
}
},
{
"exact_snippets": "transfusion of packed red blood cells [PRBCs] allowed",
"criterion": "transfusion of packed red blood cells",
"requirement": {
"requirement_type": "allowance",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Hemoglobin >= 9 g/dL",
"criterion": "hemoglobin level",
"requirement": {
"requirement_type": "level",
"expected_value": {
"operator": ">=",
"value": 9,
"unit": "g/dL"
}
}
},
{
"exact_snippets": "transfusion of packed red blood cells [PRBCs] allowed",
"criterion": "transfusion of packed red blood cells",
"requirement": {
"requirement_type": "allowance",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Serum albumin >= 3.2 g/dL",
"criterions": [
{
"exact_snippets": "Serum albumin >= 3.2 g/dL",
"criterion": "serum albumin",
"requirement": {
"requirement_type": "level",
"expected_value": {
"operator": ">=",
"value": 3.2,
"unit": "g/dL"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Serum albumin >= 3.2 g/dL",
"criterion": "serum albumin",
"requirement": {
"requirement_type": "level",
"expected_value": {
"operator": ">=",
"value": 3.2,
"unit": "g/dL"
}
}
}
]
}
},
{
"identified_line": {
"line": "* Lipase and amylase =< 2.0 x ULN and no radiologic (on baseline anatomical imaging) or clinical evidence of pancreatitis",
"criterions": [
{
"exact_snippets": "Lipase ... =< 2.0 x ULN",
"criterion": "lipase level",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "<=",
"value": 2.0,
"unit": "x ULN"
}
}
},
{
"exact_snippets": "amylase =< 2.0 x ULN",
"criterion": "amylase level",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "<=",
"value": 2.0,
"unit": "x ULN"
}
}
},
{
"exact_snippets": "no radiologic (on baseline anatomical imaging) ... evidence of pancreatitis",
"criterion": "radiologic evidence of pancreatitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "no ... clinical evidence of pancreatitis",
"criterion": "clinical evidence of pancreatitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Lipase ... =< 2.0 x ULN",
"criterion": "lipase level",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "<=",
"value": 2.0,
"unit": "x ULN"
}
}
},
{
"exact_snippets": "amylase =< 2.0 x ULN",
"criterion": "amylase level",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": "<=",
"value": 2.0,
"unit": "x ULN"
}
}
}
]
},
{
"or_criteria": [
{
"exact_snippets": "no radiologic (on baseline anatomical imaging) ... evidence of pancreatitis",
"criterion": "radiologic evidence of pancreatitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "no ... clinical evidence of pancreatitis",
"criterion": "clinical evidence of pancreatitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
}
]
}
},
{
"identified_line": {
"line": "* Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed",
"criterions": [
{
"exact_snippets": "Prior treatment with MET or VEGFR inhibitors is allowed.",
"criterion": "prior treatment with MET or VEGFR inhibitors",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "prior cabozantinib will not be allowed.",
"criterion": "prior cabozantinib treatment",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed",
"criterion": "prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 treatment",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Prior treatment with MET or VEGFR inhibitors is allowed.",
"criterion": "prior treatment with MET or VEGFR inhibitors",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"not_criteria": {
"exact_snippets": "prior cabozantinib will not be allowed.",
"criterion": "prior cabozantinib treatment",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
}
]
},
{
"not_criteria": {
"exact_snippets": "patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed",
"criterion": "prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 treatment",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
}
]
}
]
}
},
{
"identified_line": {
"line": "* No prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors with the exception of patients with \"urothelial carcinoma\" histology (cohorts D, H, J, L)",
"criterions": [
{
"exact_snippets": "No prior treatment with any therapy on the PD-1/PD-L1 axis",
"criterion": "prior treatment with PD-1/PD-L1 axis therapy",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "No prior treatment with ... anti- CTLA-4/CTLA-4 inhibitors",
"criterion": "prior treatment with anti-CTLA-4/CTLA-4 inhibitors",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"condition": {
"and_criteria": [
{
"exact_snippets": "No prior treatment with any therapy on the PD-1/PD-L1 axis",
"criterion": "prior treatment with PD-1/PD-L1 axis therapy",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "No prior treatment with ... anti- CTLA-4/CTLA-4 inhibitors",
"criterion": "prior treatment with anti-CTLA-4/CTLA-4 inhibitors",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"then_criteria": null,
"else_criteria": {
"exact_snippets": "patients with \"urothelial carcinoma\" histology (cohorts D, H, J, L)",
"criterion": "urothelial carcinoma histology",
"requirement": {
"requirement_type": "cohort inclusion",
"expected_value": [
"D",
"H",
"J",
"L"
]
}
}
}
},
{
"identified_line": {
"line": "* Human immunodeficiency virus (HIV)-positive patients are eligible if on stable dose of highly active antiretroviral therapy (HAART), no clinically significant drug-drug interactions are anticipated with the current HAART regimen, CD4 counts are greater than 350 and viral load is undetectable",
"criterions": [
{
"exact_snippets": "Human immunodeficiency virus (HIV)-positive patients",
"criterion": "HIV status",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "on stable dose of highly active antiretroviral therapy (HAART)",
"criterion": "HAART regimen",
"requirement": {
"requirement_type": "stability",
"expected_value": true
}
},
{
"exact_snippets": "no clinically significant drug-drug interactions are anticipated with the current HAART regimen",
"criterion": "drug-drug interactions",
"requirement": {
"requirement_type": "significance",
"expected_value": false
}
},
{
"exact_snippets": "CD4 counts are greater than 350",
"criterion": "CD4 count",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">",
"value": 350,
"unit": "N/A"
}
}
},
{
"exact_snippets": "viral load is undetectable",
"criterion": "viral load",
"requirement": {
"requirement_type": "detectability",
"expected_value": false
}
}
]
},
"logical_structure": {
"condition": {
"exact_snippets": "Human immunodeficiency virus (HIV)-positive patients",
"criterion": "HIV status",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
"then_criteria": {
"and_criteria": [
{
"exact_snippets": "on stable dose of highly active antiretroviral therapy (HAART)",
"criterion": "HAART regimen",
"requirement": {
"requirement_type": "stability",
"expected_value": true
}
},
{
"exact_snippets": "no clinically significant drug-drug interactions are anticipated with the current HAART regimen",
"criterion": "drug-drug interactions",
"requirement": {
"requirement_type": "significance",
"expected_value": false
}
},
{
"exact_snippets": "CD4 counts are greater than 350",
"criterion": "CD4 count",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">",
"value": 350,
"unit": "N/A"
}
}
},
{
"exact_snippets": "viral load is undetectable",
"criterion": "viral load",
"requirement": {
"requirement_type": "detectability",
"expected_value": false
}
}
]
},
"else_criteria": null
}
},
{
"identified_line": {
"line": "* Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication only and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies etc. are eligible but should be considered for rheumatologic evaluation for the presence of target organ involvement and potential need for systemic treatment",
"criterions": [
{
"exact_snippets": "Patients with rheumatoid arthritis",
"criterion": "rheumatoid arthritis",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "other rheumatologic arthropathies",
"criterion": "rheumatologic arthropathies",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "Sjogren's syndrome",
"criterion": "Sjogren's syndrome",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "psoriasis controlled with topical medication only",
"criterion": "psoriasis",
"requirement": {
"requirement_type": "control method",
"expected_value": "topical medication only"
}
},
{
"exact_snippets": "patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies",
"criterion": "positive serology",
"requirement": {
"requirement_type": "presence",
"expected_value": [
"antinuclear antibodies (ANA)",
"anti-thyroid antibodies"
]
}
},
{
"exact_snippets": "rheumatologic evaluation for the presence of target organ involvement",
"criterion": "target organ involvement",
"requirement": {
"requirement_type": "evaluation",
"expected_value": "rheumatologic"
}
},
{
"exact_snippets": "potential need for systemic treatment",
"criterion": "systemic treatment",
"requirement": {
"requirement_type": "potential need",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Patients with rheumatoid arthritis",
"criterion": "rheumatoid arthritis",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "rheumatologic evaluation for the presence of target organ involvement",
"criterion": "target organ involvement",
"requirement": {
"requirement_type": "evaluation",
"expected_value": "rheumatologic"
}
},
{
"exact_snippets": "potential need for systemic treatment",
"criterion": "systemic treatment",
"requirement": {
"requirement_type": "potential need",
"expected_value": true
}
}
]
},
{
"and_criteria": [
{
"exact_snippets": "other rheumatologic arthropathies",
"criterion": "rheumatologic arthropathies",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "rheumatologic evaluation for the presence of target organ involvement",
"criterion": "target organ involvement",
"requirement": {
"requirement_type": "evaluation",
"expected_value": "rheumatologic"
}
},
{
"exact_snippets": "potential need for systemic treatment",
"criterion": "systemic treatment",
"requirement": {
"requirement_type": "potential need",
"expected_value": true
}
}
]
},
{
"and_criteria": [
{
"exact_snippets": "Sjogren's syndrome",
"criterion": "Sjogren's syndrome",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "rheumatologic evaluation for the presence of target organ involvement",
"criterion": "target organ involvement",
"requirement": {
"requirement_type": "evaluation",
"expected_value": "rheumatologic"
}
},
{
"exact_snippets": "potential need for systemic treatment",
"criterion": "systemic treatment",
"requirement": {
"requirement_type": "potential need",
"expected_value": true
}
}
]
},
{
"exact_snippets": "psoriasis controlled with topical medication only",
"criterion": "psoriasis",
"requirement": {
"requirement_type": "control method",
"expected_value": "topical medication only"
}
},
{
"exact_snippets": "patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies",
"criterion": "positive serology",
"requirement": {
"requirement_type": "presence",
"expected_value": [
"antinuclear antibodies (ANA)",
"anti-thyroid antibodies"
]
}
}
]
}
]
}
},
{
"identified_line": {
"line": "* Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones or medications (e.g. thyroiditis managed with propylthiouracil [PTU] or methimazole) including physiologic oral corticosteroids are eligible",
"criterions": [
{
"exact_snippets": "Patients with vitiligo",
"criterion": "vitiligo",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "endocrine deficiencies including thyroiditis",
"criterion": "endocrine deficiencies",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "thyroiditis managed with replacement hormones or medications (e.g. thyroiditis managed with propylthiouracil [PTU] or methimazole)",
"criterion": "thyroiditis management",
"requirement": {
"requirement_type": "medication",
"expected_value": [
"replacement hormones",
"propylthiouracil [PTU]",
"methimazole"
]
}
},
{
"exact_snippets": "physiologic oral corticosteroids",
"criterion": "physiologic oral corticosteroids",
"requirement": {
"requirement_type": "medication",
"expected_value": true
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Patients with vitiligo",
"criterion": "vitiligo",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
{
"and_criteria": [
{
"exact_snippets": "endocrine deficiencies including thyroiditis",
"criterion": "endocrine deficiencies",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"or_criteria": [
{
"exact_snippets": "thyroiditis managed with replacement hormones or medications (e.g. thyroiditis managed with propylthiouracil [PTU] or methimazole)",
"criterion": "thyroiditis management",
"requirement": {
"requirement_type": "medication",
"expected_value": [
"replacement hormones",
"propylthiouracil [PTU]",
"methimazole"
]
}
},
{
"exact_snippets": "physiologic oral corticosteroids",
"criterion": "physiologic oral corticosteroids",
"requirement": {
"requirement_type": "medication",
"expected_value": true
}
}
]
}
]
}
]
}
},
{
"identified_line": {
"line": "* Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess, and gastrointestinal (GI) obstruction, within 12 months are not eligible",
"criterions": [
{
"exact_snippets": "evidence of active or acute diverticulitis",
"criterion": "diverticulitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "intra-abdominal abscess",
"criterion": "intra-abdominal abscess",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "gastrointestinal (GI) obstruction",
"criterion": "gastrointestinal obstruction",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"not_criteria": {
"and_criteria": [
{
"exact_snippets": "evidence of active or acute diverticulitis",
"criterion": "diverticulitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "intra-abdominal abscess",
"criterion": "intra-abdominal abscess",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "gastrointestinal (GI) obstruction",
"criterion": "gastrointestinal obstruction",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
}
}
]
}
},
{
"identified_line": {
"line": "* Women of childbearing potential must have a negative pregnancy test =< 7 days prior to registration",
"criterions": [
{
"exact_snippets": "Women of childbearing potential",
"criterion": "childbearing potential",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "negative pregnancy test",
"criterion": "pregnancy test",
"requirement": {
"requirement_type": "result",
"expected_value": "negative"
}
},
{
"exact_snippets": "=< 7 days prior to registration",
"criterion": "pregnancy test timing",
"requirement": {
"requirement_type": "timing",
"expected_value": {
"operator": "<=",
"value": 7,
"unit": "days"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Women of childbearing potential",
"criterion": "childbearing potential",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "negative pregnancy test",
"criterion": "pregnancy test",
"requirement": {
"requirement_type": "result",
"expected_value": "negative"
}
}
]
},
{
"exact_snippets": "=< 7 days prior to registration",
"criterion": "pregnancy test timing",
"requirement": {
"requirement_type": "timing",
"expected_value": {
"operator": "<=",
"value": 7,
"unit": "days"
}
}
}
]
}
},
{
"identified_line": {
"line": "* Pregnant women may not participate in this study because with cabozantinib, nivolumab, and ipilimumab have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib, nivolumab, and ipilimumab, breastfeeding should be discontinued if the mother is treated with these agents",
"criterions": [
{
"exact_snippets": "Pregnant women may not participate",
"criterion": "pregnancy",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "breastfeeding should be discontinued",
"criterion": "breastfeeding",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"not_criteria": {
"exact_snippets": "Pregnant women may not participate",
"criterion": "pregnancy",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
},
{
"not_criteria": {
"exact_snippets": "breastfeeding should be discontinued",
"criterion": "breastfeeding",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
}
]
}
},
{
"identified_line": {
"line": "* The patient has received no cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 2 weeks before the first dose of study treatment",
"criterions": [
{
"exact_snippets": "The patient has received no cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) ... within 2 weeks before the first dose of study treatment",
"criterion": "cytotoxic chemotherapy",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"operator": ">=",
"value": 2,
"unit": "weeks"
}
}
},
{
"exact_snippets": "The patient has received no ... biologic agents (e.g., cytokines or antibodies) within 2 weeks before the first dose of study treatment",
"criterion": "biologic agents",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"operator": ">=",
"value": 2,
"unit": "weeks"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "The patient has received no cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) ... within 2 weeks before the first dose of study treatment",
"criterion": "cytotoxic chemotherapy",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"operator": ">=",
"value": 2,
"unit": "weeks"
}
}
},
{
"exact_snippets": "The patient has received no ... biologic agents (e.g., cytokines or antibodies) within 2 weeks before the first dose of study treatment",
"criterion": "biologic agents",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"operator": ">=",
"value": 2,
"unit": "weeks"
}
}
}
]
}
]
}
},
{
"identified_line": {
"line": "* The patient has received no radiation therapy:",
"criterions": [
{
"exact_snippets": "The patient has received no radiation therapy",
"criterion": "radiation therapy",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "The patient has received no radiation therapy",
"criterion": "radiation therapy",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
}
},
{
"identified_line": {
"line": "* To the lungs and mediastinum or abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy",
"criterions": [
{
"exact_snippets": "To the lungs and mediastinum or abdomen within 4 weeks before the first dose of study treatment",
"criterion": "radiation therapy to lungs, mediastinum, or abdomen",
"requirement": {
"requirement_type": "time since treatment",
"expected_value": {
"operator": "<=",
"value": 4,
"unit": "weeks"
}
}
},
{
"exact_snippets": "has ongoing complications",
"criterion": "ongoing complications from prior radiation therapy",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "is healing from prior radiation therapy",
"criterion": "healing from prior radiation therapy",
"requirement": {
"requirement_type": "status",
"expected_value": "healing"
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "To the lungs and mediastinum or abdomen within 4 weeks before the first dose of study treatment",
"criterion": "radiation therapy to lungs, mediastinum, or abdomen",
"requirement": {
"requirement_type": "time since treatment",
"expected_value": {
"operator": "<=",
"value": 4,
"unit": "weeks"
}
}
}
]
},
{
"exact_snippets": "has ongoing complications",
"criterion": "ongoing complications from prior radiation therapy",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "is healing from prior radiation therapy",
"criterion": "healing from prior radiation therapy",
"requirement": {
"requirement_type": "status",
"expected_value": "healing"
}
}
]
}
},
{
"identified_line": {
"line": "* To brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT), and 2 weeks for stereotactic body radiation therapy (SBRT) before the first dose of study treatment",
"criterions": [
{
"exact_snippets": "brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT)",
"criterion": "brain metastasis treatment timing for WBXRT",
"requirement": {
"requirement_type": "time since treatment",
"expected_value": {
"operator": "<=",
"value": 3,
"unit": "weeks"
}
}
},
{
"exact_snippets": "brain metastasis ... 2 weeks for stereotactic body radiation therapy (SBRT)",
"criterion": "brain metastasis treatment timing for SBRT",
"requirement": {
"requirement_type": "time since treatment",
"expected_value": {
"operator": "<=",
"value": 2,
"unit": "weeks"
}
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"exact_snippets": "brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT)",
"criterion": "brain metastasis treatment timing for WBXRT",
"requirement": {
"requirement_type": "time since treatment",
"expected_value": {
"operator": "<=",
"value": 3,
"unit": "weeks"
}
}
},
{
"exact_snippets": "brain metastasis ... 2 weeks for stereotactic body radiation therapy (SBRT)",
"criterion": "brain metastasis treatment timing for SBRT",
"requirement": {
"requirement_type": "time since treatment",
"expected_value": {
"operator": "<=",
"value": 2,
"unit": "weeks"
}
}
}
]
}
},
{
"identified_line": {
"line": "* To the abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy",
"criterions": [
{
"exact_snippets": "To the abdomen within 4 weeks before the first dose of study treatment",
"criterion": "radiation therapy to the abdomen",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"operator": "<",
"value": 4,
"unit": "weeks"
}
}
},
{
"exact_snippets": "ongoing complications",
"criterion": "complications from prior radiation therapy",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "healing from prior radiation therapy",
"criterion": "healing from prior radiation therapy",
"requirement": {
"requirement_type": "status",
"expected_value": "healing"
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "To the abdomen within 4 weeks before the first dose of study treatment",
"criterion": "radiation therapy to the abdomen",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"operator": "<",
"value": 4,
"unit": "weeks"
}
}
}
]
},
{
"and_criteria": [
{
"exact_snippets": "ongoing complications",
"criterion": "complications from prior radiation therapy",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
{
"and_criteria": [
{
"exact_snippets": "healing from prior radiation therapy",
"criterion": "healing from prior radiation therapy",
"requirement": {
"requirement_type": "status",
"expected_value": "healing"
}
}
]
}
]
}
},
{
"identified_line": {
"line": "* To any other site(s) within 2 weeks before the first dose of study treatment",
"criterions": [
{
"exact_snippets": "To any other site(s) within 2 weeks before the first dose of study treatment",
"criterion": "treatment at other sites",
"requirement": {
"requirement_type": "time frame",
"expected_value": {
"operator": "<=",
"value": 2,
"unit": "weeks"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "To any other site(s) within 2 weeks before the first dose of study treatment",
"criterion": "treatment at other sites",
"requirement": {
"requirement_type": "time frame",
"expected_value": {
"operator": "<=",
"value": 2,
"unit": "weeks"
}
}
}
]
}
},
{
"identified_line": {
"line": "* The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment",
"criterions": [
{
"exact_snippets": "no radionuclide treatment within 6 weeks of the first dose of study treatment",
"criterion": "radionuclide treatment",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"operator": ">=",
"value": 6,
"unit": "weeks"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "no radionuclide treatment within 6 weeks of the first dose of study treatment",
"criterion": "radionuclide treatment",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"operator": ">=",
"value": 6,
"unit": "weeks"
}
}
}
]
}
},
{
"identified_line": {
"line": "* The patient has received no prior treatment with a small molecule kinase inhibitor within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment",
"criterions": [
{
"exact_snippets": "The patient has received no prior treatment with a small molecule kinase inhibitor",
"criterion": "prior treatment with a small molecule kinase inhibitor",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment",
"criterion": "time since last treatment with a small molecule kinase inhibitor",
"requirement": {
"requirement_type": "duration",
"expected_value": "14 days or five half-lives, whichever is longer"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"not_criteria": {
"exact_snippets": "The patient has received no prior treatment with a small molecule kinase inhibitor",
"criterion": "prior treatment with a small molecule kinase inhibitor",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
},
{
"not_criteria": {
"exact_snippets": "within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment",
"criterion": "time since last treatment with a small molecule kinase inhibitor",
"requirement": {
"requirement_type": "duration",
"expected_value": "14 days or five half-lives, whichever is longer"
}
}
}
]
}
},
{
"identified_line": {
"line": "* The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment. Subjects receiving gonadotropin-releasing hormone (GnRH) agonists and antagonists are allowed to participate",
"criterions": [
{
"exact_snippets": "The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment.",
"criterion": "prior hormonal therapy treatment",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"comparisons": [
{
"operator": ">",
"value": 14,
"unit": "days"
}
]
}
}
},
{
"exact_snippets": "The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment.",
"criterion": "prior hormonal therapy treatment",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": "five half-lives of the compound or active metabolites, whichever is longer"
}
},
{
"exact_snippets": "Subjects receiving gonadotropin-releasing hormone (GnRH) agonists and antagonists are allowed to participate",
"criterion": "GnRH agonists and antagonists treatment",
"requirement": {
"requirement_type": "participation allowance",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment.",
"criterion": "prior hormonal therapy treatment",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"comparisons": [
{
"operator": ">",
"value": 14,
"unit": "days"
}
]
}
}
},
{
"exact_snippets": "The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment.",
"criterion": "prior hormonal therapy treatment",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": "five half-lives of the compound or active metabolites, whichever is longer"
}
}
]
},
{
"exact_snippets": "Subjects receiving gonadotropin-releasing hormone (GnRH) agonists and antagonists are allowed to participate",
"criterion": "GnRH agonists and antagonists treatment",
"requirement": {
"requirement_type": "participation allowance",
"expected_value": true
}
}
]
}
]
}
},
{
"identified_line": {
"line": "* The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment",
"criterions": [
{
"exact_snippets": "The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment",
"criterion": "investigational agent",
"requirement": {
"requirement_type": "absence",
"expected_value": true
}
},
{
"exact_snippets": "The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment",
"criterion": "investigational agent",
"requirement": {
"requirement_type": "time since last dose",
"expected_value": {
"operator": ">=",
"value": 14,
"unit": "days"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment",
"criterion": "investigational agent",
"requirement": {
"requirement_type": "absence",
"expected_value": true
}
},
{
"exact_snippets": "The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment",
"criterion": "investigational agent",
"requirement": {
"requirement_type": "time since last dose",
"expected_value": {
"operator": ">=",
"value": 14,
"unit": "days"
}
}
}
]
}
},
{
"identified_line": {
"line": "* The patient must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies except alopecia, neuropathy and other non-clinically significant adverse events (AEs) defined as lab elevation with no associated symptoms or sequelae",
"criterions": [
{
"exact_snippets": "recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies",
"criterion": "recovery from prior therapy toxicity",
"requirement": {
"requirement_type": "severity",
"expected_value": {
"operator": "<=",
"value": 1,
"unit": "grade"
}
}
},
{
"exact_snippets": "except alopecia",
"criterion": "alopecia",
"requirement": {
"requirement_type": "exclusion",
"expected_value": true
}
},
{
"exact_snippets": "except ... neuropathy",
"criterion": "neuropathy",
"requirement": {
"requirement_type": "exclusion",
"expected_value": true
}
},
{
"exact_snippets": "except ... other non-clinically significant adverse events (AEs) defined as lab elevation with no associated symptoms or sequelae",
"criterion": "non-clinically significant adverse events",
"requirement": {
"requirement_type": "exclusion",
"expected_value": true
}
}
]
},
"logical_structure": {
"condition": {
"and_criteria": [
{
"exact_snippets": "recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies",
"criterion": "recovery from prior therapy toxicity",
"requirement": {
"requirement_type": "severity",
"expected_value": {
"operator": "<=",
"value": 1,
"unit": "grade"
}
}
}
]
},
"then_criteria": {
"and_criteria": [
{
"exact_snippets": "except alopecia",
"criterion": "alopecia",
"requirement": {
"requirement_type": "exclusion",
"expected_value": true
}
},
{
"exact_snippets": "except ... neuropathy",
"criterion": "neuropathy",
"requirement": {
"requirement_type": "exclusion",
"expected_value": true
}
},
{
"exact_snippets": "except ... other non-clinically significant adverse events (AEs) defined as lab elevation with no associated symptoms or sequelae",
"criterion": "non-clinically significant adverse events",
"requirement": {
"requirement_type": "exclusion",
"expected_value": true
}
}
]
},
"else_criteria": null
}
},
{
"identified_line": {
"line": "* The patient may not have active brain metastases or epidural disease. Patients with brain metastases previously treated with whole brain radiation or radiosurgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility",
"criterions": [
{
"exact_snippets": "The patient may not have active brain metastases",
"criterion": "active brain metastases",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "The patient may not have ... epidural disease",
"criterion": "epidural disease",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "Patients with brain metastases previously treated with whole brain radiation or radiosurgery who are asymptomatic",
"criterion": "asymptomatic status post brain metastases treatment",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "do not require steroid treatment for at least 2 weeks before starting study treatment",
"criterion": "steroid treatment requirement",
"requirement": {
"requirement_type": "requirement",
"expected_value": false
}
},
{
"exact_snippets": "Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment",
"criterion": "neurosurgical resection or brain biopsy timing",
"requirement": {
"requirement_type": "timing",
"expected_value": {
"operator": ">=",
"value": 3,
"unit": "months"
}
}
},
{
"exact_snippets": "Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required",
"criterion": "baseline brain imaging",
"requirement": {
"requirement_type": "requirement",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"not_criteria": {
"and_criteria": [
{
"exact_snippets": "The patient may not have active brain metastases",
"criterion": "active brain metastases",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "The patient may not have ... epidural disease",
"criterion": "epidural disease",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
}
},
{
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Patients with brain metastases previously treated with whole brain radiation or radiosurgery who are asymptomatic",
"criterion": "asymptomatic status post brain metastases treatment",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "do not require steroid treatment for at least 2 weeks before starting study treatment",
"criterion": "steroid treatment requirement",
"requirement": {
"requirement_type": "requirement",
"expected_value": false
}
}
]
},
{
"exact_snippets": "Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment",
"criterion": "neurosurgical resection or brain biopsy timing",
"requirement": {
"requirement_type": "timing",
"expected_value": {
"operator": ">=",
"value": 3,
"unit": "months"
}
}
}
]
},
{
"exact_snippets": "Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required",
"criterion": "baseline brain imaging",
"requirement": {
"requirement_type": "requirement",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* No concomitant treatment with warfarin. Aspirin (up to 325 mg/day), thrombin or factor Xa inhibitors, low-dose warfarin (=< 1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted",
"criterions": [
{
"exact_snippets": "No concomitant treatment with warfarin",
"criterion": "concomitant treatment with warfarin",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "Aspirin (up to 325 mg/day) ... are permitted",
"criterion": "aspirin",
"requirement": {
"requirement_type": "dosage",
"expected_value": {
"operator": "<=",
"value": 325,
"unit": "mg/day"
}
}
},
{
"exact_snippets": "thrombin or factor Xa inhibitors ... are permitted",
"criterion": "thrombin or factor Xa inhibitors",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "low-dose warfarin (=< 1 mg/day) ... are permitted",
"criterion": "low-dose warfarin",
"requirement": {
"requirement_type": "dosage",
"expected_value": {
"operator": "<=",
"value": 1,
"unit": "mg/day"
}
}
},
{
"exact_snippets": "prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted",
"criterion": "low molecular weight heparin (LMWH)",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"not_criteria": {
"exact_snippets": "No concomitant treatment with warfarin",
"criterion": "concomitant treatment with warfarin",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
},
{
"or_criteria": [
{
"exact_snippets": "Aspirin (up to 325 mg/day) ... are permitted",
"criterion": "aspirin",
"requirement": {
"requirement_type": "dosage",
"expected_value": {
"operator": "<=",
"value": 325,
"unit": "mg/day"
}
}
},
{
"exact_snippets": "thrombin or factor Xa inhibitors ... are permitted",
"criterion": "thrombin or factor Xa inhibitors",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "low-dose warfarin (=< 1 mg/day) ... are permitted",
"criterion": "low-dose warfarin",
"requirement": {
"requirement_type": "dosage",
"expected_value": {
"operator": "<=",
"value": 1,
"unit": "mg/day"
}
}
},
{
"exact_snippets": "prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted",
"criterion": "low molecular weight heparin (LMWH)",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
]
}
},
{
"identified_line": {
"line": "* No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort) or strong CYP3A4 inhibitors",
"criterions": [
{
"exact_snippets": "No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort)",
"criterion": "chronic concomitant treatment with strong CYP3A4 inducers",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "No chronic concomitant treatment with ... strong CYP3A4 inhibitors",
"criterion": "chronic concomitant treatment with strong CYP3A4 inhibitors",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort)",
"criterion": "chronic concomitant treatment with strong CYP3A4 inducers",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "No chronic concomitant treatment with ... strong CYP3A4 inhibitors",
"criterion": "chronic concomitant treatment with strong CYP3A4 inhibitors",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
}
},
{
"identified_line": {
"line": "* Because the lists of these agents are constantly changing, it is important to regularly consult medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product",
"criterions": [
{
"exact_snippets": "counseled on the risk of interactions with other agents",
"criterion": "risk of interactions with other agents",
"requirement": {
"requirement_type": "counseling",
"expected_value": true
}
},
{
"exact_snippets": "if new medications need to be prescribed",
"criterion": "new medications",
"requirement": {
"requirement_type": "prescription",
"expected_value": true
}
},
{
"exact_snippets": "if the patient is considering a new over-the-counter medicine or herbal product",
"criterion": "new over-the-counter medicine or herbal product",
"requirement": {
"requirement_type": "consideration",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "counseled on the risk of interactions with other agents",
"criterion": "risk of interactions with other agents",
"requirement": {
"requirement_type": "counseling",
"expected_value": true
}
},
{
"exact_snippets": "if new medications need to be prescribed",
"criterion": "new medications",
"requirement": {
"requirement_type": "prescription",
"expected_value": true
}
}
]
},
{
"exact_snippets": "if the patient is considering a new over-the-counter medicine or herbal product",
"criterion": "new over-the-counter medicine or herbal product",
"requirement": {
"requirement_type": "consideration",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment",
"criterions": [
{
"exact_snippets": "Clinically-significant gastrointestinal bleeding",
"criterion": "gastrointestinal bleeding",
"requirement": {
"requirement_type": "severity",
"expected_value": "clinically-significant"
}
},
{
"exact_snippets": "within 6 months before the first dose of study treatment",
"criterion": "time since last gastrointestinal bleeding",
"requirement": {
"requirement_type": "time since last occurrence",
"expected_value": {
"operator": "<=",
"value": 6,
"unit": "months"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Clinically-significant gastrointestinal bleeding",
"criterion": "gastrointestinal bleeding",
"requirement": {
"requirement_type": "severity",
"expected_value": "clinically-significant"
}
},
{
"exact_snippets": "within 6 months before the first dose of study treatment",
"criterion": "time since last gastrointestinal bleeding",
"requirement": {
"requirement_type": "time since last occurrence",
"expected_value": {
"operator": "<=",
"value": 6,
"unit": "months"
}
}
}
]
}
},
{
"identified_line": {
"line": "* Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood per day within 1 months before the first dose of study treatment",
"criterions": [
{
"exact_snippets": "Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood per day",
"criterion": "hemoptysis",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 2.5,
"unit": "mL"
}
}
},
{
"exact_snippets": "within 1 months before the first dose of study treatment",
"criterion": "timeframe before first dose",
"requirement": {
"requirement_type": "duration",
"expected_value": {
"operator": "<=",
"value": 1,
"unit": "months"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood per day",
"criterion": "hemoptysis",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 2.5,
"unit": "mL"
}
}
},
{
"exact_snippets": "within 1 months before the first dose of study treatment",
"criterion": "timeframe before first dose",
"requirement": {
"requirement_type": "duration",
"expected_value": {
"operator": "<=",
"value": 1,
"unit": "months"
}
}
}
]
}
},
{
"identified_line": {
"line": "* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment",
"criterions": [
{
"exact_snippets": "signs indicative of pulmonary hemorrhage",
"criterion": "pulmonary hemorrhage",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "within 3 months before the first dose of study treatment",
"criterion": "time since last pulmonary hemorrhage",
"requirement": {
"requirement_type": "time frame",
"expected_value": {
"comparisons": [
{
"operator": "<=",
"value": 3,
"unit": "months"
}
]
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "signs indicative of pulmonary hemorrhage",
"criterion": "pulmonary hemorrhage",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "within 3 months before the first dose of study treatment",
"criterion": "time since last pulmonary hemorrhage",
"requirement": {
"requirement_type": "time frame",
"expected_value": {
"comparisons": [
{
"operator": "<=",
"value": 3,
"unit": "months"
}
]
}
}
}
]
}
},
{
"identified_line": {
"line": "* The patient has no tumor invading any major blood vessels",
"criterions": [
{
"exact_snippets": "no tumor invading any major blood vessels",
"criterion": "tumor invasion of major blood vessels",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "no tumor invading any major blood vessels",
"criterion": "tumor invasion of major blood vessels",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
}
},
{
"identified_line": {
"line": "* The patient has no uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:",
"criterions": [
{
"exact_snippets": "uncontrolled, significant intercurrent or recent illness",
"criterion": "uncontrolled illness",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "uncontrolled, significant intercurrent or recent illness",
"criterion": "significant intercurrent illness",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "uncontrolled, significant intercurrent or recent illness",
"criterion": "recent illness",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "uncontrolled, significant intercurrent or recent illness",
"criterion": "uncontrolled illness",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "uncontrolled, significant intercurrent or recent illness",
"criterion": "significant intercurrent illness",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
{
"exact_snippets": "uncontrolled, significant intercurrent or recent illness",
"criterion": "recent illness",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
}
},
{
"identified_line": {
"line": "* Cardiovascular disorders including:",
"criterions": [
{
"exact_snippets": "Cardiovascular disorders",
"criterion": "cardiovascular disorders",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Cardiovascular disorders",
"criterion": "cardiovascular disorders",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization. Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard",
"criterions": [
{
"exact_snippets": "corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms",
"criterion": "corrected QT interval (QTcF)",
"requirement": {
"requirement_type": "value",
"expected_value": {
"operator": ">",
"value": 500,
"unit": "ms"
}
}
},
{
"exact_snippets": "average of these three consecutive results for QTcF is =< 500 ms",
"criterion": "average corrected QT interval (QTcF)",
"requirement": {
"requirement_type": "value",
"expected_value": {
"operator": "<=",
"value": 500,
"unit": "ms"
}
}
}
]
},
"logical_structure": {
"condition": {
"and_criteria": [
{
"exact_snippets": "corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms",
"criterion": "corrected QT interval (QTcF)",
"requirement": {
"requirement_type": "value",
"expected_value": {
"operator": ">",
"value": 500,
"unit": "ms"
}
}
}
]
},
"then_criteria": {
"exact_snippets": "average of these three consecutive results for QTcF is =< 500 ms",
"criterion": "average corrected QT interval (QTcF)",
"requirement": {
"requirement_type": "value",
"expected_value": {
"operator": "<=",
"value": 500,
"unit": "ms"
}
}
},
"else_criteria": null
}
},
{
"identified_line": {
"line": "* Any history of congenital long QT syndrome",
"criterions": [
{
"exact_snippets": "Any history of congenital long QT syndrome",
"criterion": "congenital long QT syndrome",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Any history of congenital long QT syndrome",
"criterion": "congenital long QT syndrome",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Any of the following within 6 months before registration of study treatment:",
"criterions": [
{
"exact_snippets": "Any of the following within 6 months before registration of study treatment",
"criterion": "time since event",
"requirement": {
"requirement_type": "time frame",
"expected_value": {
"comparisons": [
{
"operator": "<=",
"value": 6,
"unit": "months"
}
]
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Any of the following within 6 months before registration of study treatment",
"criterion": "time since event",
"requirement": {
"requirement_type": "time frame",
"expected_value": {
"comparisons": [
{
"operator": "<=",
"value": 6,
"unit": "months"
}
]
}
}
}
]
}
},
{
"identified_line": {
"line": "* Unstable angina pectoris",
"criterions": [
{
"exact_snippets": "Unstable angina pectoris",
"criterion": "unstable angina pectoris",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Unstable angina pectoris",
"criterion": "unstable angina pectoris",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Clinically-significant cardiac arrhythmias (patients with atrial fibrillation are eligible)",
"criterions": [
{
"exact_snippets": "Clinically-significant cardiac arrhythmias",
"criterion": "cardiac arrhythmias",
"requirement": {
"requirement_type": "severity",
"expected_value": "clinically-significant"
}
},
{
"exact_snippets": "patients with atrial fibrillation are eligible",
"criterion": "atrial fibrillation",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"exact_snippets": "patients with atrial fibrillation are eligible",
"criterion": "atrial fibrillation",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"not_criteria": {
"exact_snippets": "Clinically-significant cardiac arrhythmias",
"criterion": "cardiac arrhythmias",
"requirement": {
"requirement_type": "severity",
"expected_value": "clinically-significant"
}
}
}
]
}
},
{
"identified_line": {
"line": "* Stroke (including transient ischemic attack [TIA], or other ischemic event)",
"criterions": [
{
"exact_snippets": "Stroke (including transient ischemic attack [TIA], or other ischemic event)",
"criterion": "stroke",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "transient ischemic attack [TIA]",
"criterion": "transient ischemic attack",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "other ischemic event",
"criterion": "other ischemic event",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"exact_snippets": "Stroke (including transient ischemic attack [TIA], or other ischemic event)",
"criterion": "stroke",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "transient ischemic attack [TIA]",
"criterion": "transient ischemic attack",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "other ischemic event",
"criterion": "other ischemic event",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
}
},
{
"identified_line": {
"line": "* Myocardial infarction",
"criterions": [
{
"exact_snippets": "Myocardial infarction",
"criterion": "myocardial infarction",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Myocardial infarction",
"criterion": "myocardial infarction",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Cardiomyopathy",
"criterions": [
{
"exact_snippets": "Cardiomyopathy",
"criterion": "cardiomyopathy",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Cardiomyopathy",
"criterion": "cardiomyopathy",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* No significant gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:",
"criterions": [
{
"exact_snippets": "No significant gastrointestinal disorders",
"criterion": "gastrointestinal disorders",
"requirement": {
"requirement_type": "severity",
"expected_value": "not significant"
}
},
{
"exact_snippets": "high risk of perforation",
"criterion": "risk of perforation",
"requirement": {
"requirement_type": "risk",
"expected_value": "not high"
}
},
{
"exact_snippets": "high risk of ... fistula formation",
"criterion": "risk of fistula formation",
"requirement": {
"requirement_type": "risk",
"expected_value": "not high"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "No significant gastrointestinal disorders",
"criterion": "gastrointestinal disorders",
"requirement": {
"requirement_type": "severity",
"expected_value": "not significant"
}
},
{
"or_criteria": [
{
"exact_snippets": "high risk of perforation",
"criterion": "risk of perforation",
"requirement": {
"requirement_type": "risk",
"expected_value": "not high"
}
},
{
"exact_snippets": "high risk of ... fistula formation",
"criterion": "risk of fistula formation",
"requirement": {
"requirement_type": "risk",
"expected_value": "not high"
}
}
]
}
]
}
]
}
},
{
"identified_line": {
"line": "* Any of the following that have not resolved within 28 days before the first dose of study treatment:",
"criterions": [
{
"exact_snippets": "resolved within 28 days before the first dose of study treatment",
"criterion": "condition resolution",
"requirement": {
"requirement_type": "time frame",
"expected_value": {
"operator": "<=",
"value": 28,
"unit": "days"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "resolved within 28 days before the first dose of study treatment",
"criterion": "condition resolution",
"requirement": {
"requirement_type": "time frame",
"expected_value": {
"operator": "<=",
"value": 28,
"unit": "days"
}
}
}
]
}
},
{
"identified_line": {
"line": "* Active peptic ulcer disease",
"criterions": [
{
"exact_snippets": "Active peptic ulcer disease",
"criterion": "peptic ulcer disease",
"requirement": {
"requirement_type": "activity",
"expected_value": "active"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Active peptic ulcer disease",
"criterion": "peptic ulcer disease",
"requirement": {
"requirement_type": "activity",
"expected_value": "active"
}
}
]
}
},
{
"identified_line": {
"line": "* Acute diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or malabsorption syndrome",
"criterions": [
{
"exact_snippets": "Acute diverticulitis",
"criterion": "acute diverticulitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "cholecystitis",
"criterion": "cholecystitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "symptomatic cholangitis",
"criterion": "symptomatic cholangitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "appendicitis",
"criterion": "appendicitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "malabsorption syndrome",
"criterion": "malabsorption syndrome",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"and_criteria": [
{
"not_criteria": {
"exact_snippets": "Acute diverticulitis",
"criterion": "acute diverticulitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
},
{
"not_criteria": {
"exact_snippets": "cholecystitis",
"criterion": "cholecystitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
},
{
"not_criteria": {
"exact_snippets": "symptomatic cholangitis",
"criterion": "symptomatic cholangitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
},
{
"not_criteria": {
"exact_snippets": "appendicitis",
"criterion": "appendicitis",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
}
]
},
{
"not_criteria": {
"exact_snippets": "malabsorption syndrome",
"criterion": "malabsorption syndrome",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
}
]
}
},
{
"identified_line": {
"line": "* None of the following within 2 years before the first dose of study treatment:",
"criterions": [
{
"exact_snippets": "None of the following within 2 years before the first dose of study treatment",
"criterion": "time since last treatment",
"requirement": {
"requirement_type": "duration",
"expected_value": {
"comparisons": [
{
"operator": ">=",
"value": 2,
"unit": "years"
}
]
}
}
}
]
},
"logical_structure": {
"not_criteria": {
"and_criteria": [
{
"exact_snippets": "None of the following within 2 years before the first dose of study treatment",
"criterion": "time since last treatment",
"requirement": {
"requirement_type": "duration",
"expected_value": {
"comparisons": [
{
"operator": ">=",
"value": 2,
"unit": "years"
}
]
}
}
}
]
}
}
},
{
"identified_line": {
"line": "* Abdominal fistula or genitourinary fistula",
"criterions": [
{
"exact_snippets": "Abdominal fistula",
"criterion": "abdominal fistula",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "genitourinary fistula",
"criterion": "genitourinary fistula",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"exact_snippets": "Abdominal fistula",
"criterion": "abdominal fistula",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "genitourinary fistula",
"criterion": "genitourinary fistula",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Gastrointestinal perforation",
"criterions": [
{
"exact_snippets": "Gastrointestinal perforation",
"criterion": "gastrointestinal perforation",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Gastrointestinal perforation",
"criterion": "gastrointestinal perforation",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Bowel obstruction or gastric outlet obstruction",
"criterions": [
{
"exact_snippets": "Bowel obstruction",
"criterion": "bowel obstruction",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "gastric outlet obstruction",
"criterion": "gastric outlet obstruction",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"exact_snippets": "Bowel obstruction",
"criterion": "bowel obstruction",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "gastric outlet obstruction",
"criterion": "gastric outlet obstruction",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 2 years before the first dose of study treatment",
"criterions": [
{
"exact_snippets": "Intra-abdominal abscess ... Complete resolution of an intra-abdominal abscess must be confirmed",
"criterion": "intra-abdominal abscess",
"requirement": {
"requirement_type": "resolution",
"expected_value": "complete"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Intra-abdominal abscess ... Complete resolution of an intra-abdominal abscess must be confirmed",
"criterion": "intra-abdominal abscess",
"requirement": {
"requirement_type": "resolution",
"expected_value": "complete"
}
}
]
}
},
{
"identified_line": {
"line": "* Disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement are not eligible",
"criterions": [
{
"exact_snippets": "Disorders associated with a high risk of fistula formation",
"criterion": "disorders associated with fistula formation",
"requirement": {
"requirement_type": "risk level",
"expected_value": "high"
}
},
{
"exact_snippets": "percutaneous endoscopic gastrostomy (PEG) tube placement",
"criterion": "PEG tube placement",
"requirement": {
"requirement_type": "eligibility",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"not_criteria": {
"and_criteria": [
{
"exact_snippets": "Disorders associated with a high risk of fistula formation",
"criterion": "disorders associated with fistula formation",
"requirement": {
"requirement_type": "risk level",
"expected_value": "high"
}
},
{
"exact_snippets": "percutaneous endoscopic gastrostomy (PEG) tube placement",
"criterion": "PEG tube placement",
"requirement": {
"requirement_type": "eligibility",
"expected_value": false
}
}
]
}
}
]
}
},
{
"identified_line": {
"line": "* No other clinically significant disorders such as:",
"criterions": [
{
"exact_snippets": "No other clinically significant disorders",
"criterion": "clinically significant disorders",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "No other clinically significant disorders",
"criterion": "clinically significant disorders",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
}
},
{
"identified_line": {
"line": "* Severe active infection requiring IV systemic treatment within 14 days before the first dose of study treatment",
"criterions": [
{
"exact_snippets": "Severe active infection requiring IV systemic treatment",
"criterion": "severe active infection",
"requirement": {
"requirement_type": "severity",
"expected_value": "severe"
}
},
{
"exact_snippets": "Severe active infection requiring IV systemic treatment",
"criterion": "severe active infection",
"requirement": {
"requirement_type": "treatment",
"expected_value": "IV systemic treatment"
}
},
{
"exact_snippets": "within 14 days before the first dose of study treatment",
"criterion": "time since last IV systemic treatment",
"requirement": {
"requirement_type": "time",
"expected_value": {
"comparisons": [
{
"operator": "<=",
"value": 14,
"unit": "days"
}
]
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Severe active infection requiring IV systemic treatment",
"criterion": "severe active infection",
"requirement": {
"requirement_type": "severity",
"expected_value": "severe"
}
},
{
"exact_snippets": "Severe active infection requiring IV systemic treatment",
"criterion": "severe active infection",
"requirement": {
"requirement_type": "treatment",
"expected_value": "IV systemic treatment"
}
}
]
},
{
"exact_snippets": "within 14 days before the first dose of study treatment",
"criterion": "time since last IV systemic treatment",
"requirement": {
"requirement_type": "time",
"expected_value": {
"comparisons": [
{
"operator": "<=",
"value": 14,
"unit": "days"
}
]
}
}
}
]
}
},
{
"identified_line": {
"line": "* Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment",
"criterions": [
{
"exact_snippets": "Serious non-healing wound/ulcer/bone fracture",
"criterion": "serious non-healing wound/ulcer/bone fracture",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "within 28 days before the first dose of study treatment",
"criterion": "time since serious non-healing wound/ulcer/bone fracture",
"requirement": {
"requirement_type": "time since occurrence",
"expected_value": {
"operator": "<=",
"value": 28,
"unit": "days"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Serious non-healing wound/ulcer/bone fracture",
"criterion": "serious non-healing wound/ulcer/bone fracture",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "within 28 days before the first dose of study treatment",
"criterion": "time since serious non-healing wound/ulcer/bone fracture",
"requirement": {
"requirement_type": "time since occurrence",
"expected_value": {
"operator": "<=",
"value": 28,
"unit": "days"
}
}
}
]
}
},
{
"identified_line": {
"line": "* History of organ or allogeneic stem cell transplant",
"criterions": [
{
"exact_snippets": "History of organ or allogeneic stem cell transplant",
"criterion": "organ transplant",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "History of organ or allogeneic stem cell transplant",
"criterion": "allogeneic stem cell transplant",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"exact_snippets": "History of organ or allogeneic stem cell transplant",
"criterion": "organ transplant",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "History of organ or allogeneic stem cell transplant",
"criterion": "allogeneic stem cell transplant",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "* Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment (for asymptomatic patients with an elevated thyroid-stimulating hormone [TSH], thyroid replacement may be initiated if clinically indicated without delaying the start of study treatment)",
"criterions": [
{
"exact_snippets": "Concurrent uncompensated hypothyroidism",
"criterion": "uncompensated hypothyroidism",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "thyroid dysfunction within 7 days before the first dose of study treatment",
"criterion": "thyroid dysfunction",
"requirement": {
"requirement_type": "time frame",
"expected_value": "within 7 days before the first dose of study treatment"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"not_criteria": {
"exact_snippets": "Concurrent uncompensated hypothyroidism",
"criterion": "uncompensated hypothyroidism",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
},
{
"not_criteria": {
"exact_snippets": "thyroid dysfunction within 7 days before the first dose of study treatment",
"criterion": "thyroid dysfunction",
"requirement": {
"requirement_type": "time frame",
"expected_value": "within 7 days before the first dose of study treatment"
}
}
}
]
}
},
{
"identified_line": {
"line": "* No history of major surgery as follows:",
"criterions": [
{
"exact_snippets": "No history of major surgery",
"criterion": "major surgery",
"requirement": {
"requirement_type": "history",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "No history of major surgery",
"criterion": "major surgery",
"requirement": {
"requirement_type": "history",
"expected_value": false
}
}
]
}
},
{
"identified_line": {
"line": "* Major surgery within 3 months of the first dose of cabozantinib; however, if there were no wound healing complications, patients with rapidly growing aggressive cancers, may start as soon as 6 weeks if wound has completely healed post-surgery",
"criterions": [
{
"exact_snippets": "Major surgery within 3 months of the first dose of cabozantinib",
"criterion": "major surgery",
"requirement": {
"requirement_type": "time since surgery",
"expected_value": {
"comparisons": [
{
"operator": "<",
"value": 3,
"unit": "months"
}
]
}
}
},
{
"exact_snippets": "no wound healing complications",
"criterion": "wound healing complications",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "rapidly growing aggressive cancers",
"criterion": "cancer growth rate",
"requirement": {
"requirement_type": "growth rate",
"expected_value": "rapidly growing aggressive"
}
},
{
"exact_snippets": "wound has completely healed post-surgery",
"criterion": "wound healing",
"requirement": {
"requirement_type": "healing status",
"expected_value": "completely healed"
}
}
]
},
"logical_structure": {
"condition": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Major surgery within 3 months of the first dose of cabozantinib",
"criterion": "major surgery",
"requirement": {
"requirement_type": "time since surgery",
"expected_value": {
"comparisons": [
{
"operator": "<",
"value": 3,
"unit": "months"
}
]
}
}
},
{
"exact_snippets": "no wound healing complications",
"criterion": "wound healing complications",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
{
"exact_snippets": "rapidly growing aggressive cancers",
"criterion": "cancer growth rate",
"requirement": {
"requirement_type": "growth rate",
"expected_value": "rapidly growing aggressive"
}
}
]
},
"then_criteria": {
"and_criteria": [
{
"exact_snippets": "Major surgery within 3 months of the first dose of cabozantinib",
"criterion": "major surgery",
"requirement": {
"requirement_type": "time since surgery",
"expected_value": {
"comparisons": [
{
"operator": "<",
"value": 1.5,
"unit": "months"
}
]
}
}
},
{
"exact_snippets": "wound has completely healed post-surgery",
"criterion": "wound healing",
"requirement": {
"requirement_type": "healing status",
"expected_value": "completely healed"
}
}
]
},
"else_criteria": {
"and_criteria": [
{
"exact_snippets": "Major surgery within 3 months of the first dose of cabozantinib",
"criterion": "major surgery",
"requirement": {
"requirement_type": "time since surgery",
"expected_value": {
"comparisons": [
{
"operator": "<",
"value": 3,
"unit": "months"
}
]
}
}
},
{
"exact_snippets": "no wound healing complications",
"criterion": "wound healing complications",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
}
}
},
{
"identified_line": {
"line": "* Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications excluding core biopsies and mediport placement",
"criterions": [
{
"exact_snippets": "Minor surgery within 1 month of the first dose of cabozantinib",
"criterion": "minor surgery",
"requirement": {
"requirement_type": "time since",
"expected_value": {
"comparisons": [
{
"operator": "<=",
"value": 1,
"unit": "month"
}
]
}
}
},
{
"exact_snippets": "wound healing complications",
"criterion": "wound healing complications",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "Minor surgery ... within 3 months of the first dose of cabozantinib if there were wound complications",
"criterion": "minor surgery with wound complications",
"requirement": {
"requirement_type": "time since",
"expected_value": {
"comparisons": [
{
"operator": "<=",
"value": 3,
"unit": "months"
}
]
}
}
},
{
"exact_snippets": "wound complications",
"criterion": "wound complications",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "excluding core biopsies and mediport placement",
"criterion": "core biopsies and mediport placement",
"requirement": {
"requirement_type": "exclusion",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Minor surgery within 1 month of the first dose of cabozantinib",
"criterion": "minor surgery",
"requirement": {
"requirement_type": "time since",
"expected_value": {
"comparisons": [
{
"operator": "<=",
"value": 1,
"unit": "month"
}
]
}
}
},
{
"exact_snippets": "wound healing complications",
"criterion": "wound healing complications",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
{
"and_criteria": [
{
"exact_snippets": "Minor surgery ... within 3 months of the first dose of cabozantinib if there were wound complications",
"criterion": "minor surgery with wound complications",
"requirement": {
"requirement_type": "time since",
"expected_value": {
"comparisons": [
{
"operator": "<=",
"value": 3,
"unit": "months"
}
]
}
}
},
{
"exact_snippets": "wound complications",
"criterion": "wound complications",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
]
},
{
"not_criteria": {
"exact_snippets": "excluding core biopsies and mediport placement",
"criterion": "core biopsies and mediport placement",
"requirement": {
"requirement_type": "exclusion",
"expected_value": true
}
}
}
]
}
},
{
"identified_line": {
"line": "* Complete wound healing from prior surgery must be confirmed before the first dose of cabozantinib irrespective of the time from surgery",
"criterions": [
{
"exact_snippets": "Complete wound healing from prior surgery must be confirmed",
"criterion": "wound healing from prior surgery",
"requirement": {
"requirement_type": "status",
"expected_value": "complete"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Complete wound healing from prior surgery must be confirmed",
"criterion": "wound healing from prior surgery",
"requirement": {
"requirement_type": "status",
"expected_value": "complete"
}
}
]
}
},
{
"identified_line": {
"line": "* No history of severe hypersensitivity reaction to any monoclonal antibody",
"criterions": [
{
"exact_snippets": "No history of severe hypersensitivity reaction to any monoclonal antibody",
"criterion": "severe hypersensitivity reaction to monoclonal antibody",
"requirement": {
"requirement_type": "history",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "No history of severe hypersensitivity reaction to any monoclonal antibody",
"criterion": "severe hypersensitivity reaction to monoclonal antibody",
"requirement": {
"requirement_type": "history",
"expected_value": false
}
}
]
}
},
{
"identified_line": {
"line": "* No evidence of active malignancy, requiring systemic treatment within 2 years of registration",
"criterions": [
{
"exact_snippets": "No evidence of active malignancy",
"criterion": "active malignancy",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "requiring systemic treatment within 2 years of registration",
"criterion": "systemic treatment for malignancy",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"comparisons": [
{
"operator": ">=",
"value": 2,
"unit": "years"
}
]
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "No evidence of active malignancy",
"criterion": "active malignancy",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "requiring systemic treatment within 2 years of registration",
"criterion": "systemic treatment for malignancy",
"requirement": {
"requirement_type": "time since last treatment",
"expected_value": {
"comparisons": [
{
"operator": ">=",
"value": 2,
"unit": "years"
}
]
}
}
}
]
}
},
{
"identified_line": {
"line": "* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, ipilimumab or other agents used in study",
"criterions": [
{
"exact_snippets": "No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, ipilimumab or other agents used in study",
"criterion": "allergic reactions to compounds",
"requirement": {
"requirement_type": "history",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, ipilimumab or other agents used in study",
"criterion": "allergic reactions to compounds",
"requirement": {
"requirement_type": "history",
"expected_value": false
}
}
]
}
},
{
"identified_line": {
"line": "* No positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. If HBV sAG is positive, subsequent ribonucleic acid (RNA) polymerase chain reaction (PCR) must be negative",
"criterions": [
{
"exact_snippets": "No positive test for hepatitis B virus surface antigen (HBV sAg)",
"criterion": "hepatitis B virus surface antigen (HBV sAg)",
"requirement": {
"requirement_type": "test result",
"expected_value": false
}
},
{
"exact_snippets": "No positive test for ... hepatitis C virus ribonucleic acid (HCV antibody)",
"criterion": "hepatitis C virus ribonucleic acid (HCV antibody)",
"requirement": {
"requirement_type": "test result",
"expected_value": false
}
},
{
"exact_snippets": "If HBV sAG is positive, subsequent ribonucleic acid (RNA) polymerase chain reaction (PCR) must be negative",
"criterion": "hepatitis B virus ribonucleic acid (RNA) polymerase chain reaction (PCR)",
"requirement": {
"requirement_type": "test result",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "No positive test for hepatitis B virus surface antigen (HBV sAg)",
"criterion": "hepatitis B virus surface antigen (HBV sAg)",
"requirement": {
"requirement_type": "test result",
"expected_value": false
}
},
{
"exact_snippets": "No positive test for ... hepatitis C virus ribonucleic acid (HCV antibody)",
"criterion": "hepatitis C virus ribonucleic acid (HCV antibody)",
"requirement": {
"requirement_type": "test result",
"expected_value": false
}
}
]
},
{
"and_criteria": [
{
"exact_snippets": "If HBV sAG is positive, subsequent ribonucleic acid (RNA) polymerase chain reaction (PCR) must be negative",
"criterion": "hepatitis B virus ribonucleic acid (RNA) polymerase chain reaction (PCR)",
"requirement": {
"requirement_type": "test result",
"expected_value": false
}
},
{
"exact_snippets": "No positive test for ... hepatitis C virus ribonucleic acid (HCV antibody)",
"criterion": "hepatitis C virus ribonucleic acid (HCV antibody)",
"requirement": {
"requirement_type": "test result",
"expected_value": false
}
}
]
}
]
}
]
}
},
{
"identified_line": {
"line": "* No patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include, but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease",
"criterions": [
{
"exact_snippets": "active autoimmune disease",
"criterion": "active autoimmune disease",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "history of autoimmune disease that might recur",
"criterion": "history of autoimmune disease",
"requirement": {
"requirement_type": "recurrence risk",
"expected_value": true
}
},
{
"exact_snippets": "affect vital organ function",
"criterion": "impact on vital organ function",
"requirement": {
"requirement_type": "impact",
"expected_value": true
}
},
{
"exact_snippets": "require immune suppressive treatment including systemic corticosteroids",
"criterion": "requirement for immune suppressive treatment",
"requirement": {
"requirement_type": "treatment necessity",
"expected_value": true
}
},
{
"exact_snippets": "history of immune related neurologic disease",
"criterion": "history of immune related neurologic disease",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "multiple sclerosis",
"criterion": "multiple sclerosis",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "autoimmune (demyelinating) neuropathy",
"criterion": "autoimmune (demyelinating) neuropathy",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "Guillain-Barre syndrome",
"criterion": "Guillain-Barre syndrome",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "myasthenia gravis",
"criterion": "myasthenia gravis",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "systemic autoimmune disease such as systemic lupus erythematosus (SLE)",
"criterion": "systemic lupus erythematosus (SLE)",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "connective tissue diseases",
"criterion": "connective tissue diseases",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "scleroderma",
"criterion": "scleroderma",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "inflammatory bowel disease (IBD)",
"criterion": "inflammatory bowel disease (IBD)",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "Crohn's",
"criterion": "Crohn's disease",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "ulcerative colitis",
"criterion": "ulcerative colitis",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "hepatitis",
"criterion": "hepatitis",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "history of toxic epidermal necrolysis (TEN)",
"criterion": "toxic epidermal necrolysis (TEN)",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "Stevens-Johnson syndrome",
"criterion": "Stevens-Johnson syndrome",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "phospholipid syndrome",
"criterion": "phospholipid syndrome",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"and_criteria": [
{
"exact_snippets": "active autoimmune disease",
"criterion": "active autoimmune disease",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "history of autoimmune disease that might recur",
"criterion": "history of autoimmune disease",
"requirement": {
"requirement_type": "recurrence risk",
"expected_value": true
}
},
{
"exact_snippets": "affect vital organ function",
"criterion": "impact on vital organ function",
"requirement": {
"requirement_type": "impact",
"expected_value": true
}
},
{
"exact_snippets": "require immune suppressive treatment including systemic corticosteroids",
"criterion": "requirement for immune suppressive treatment",
"requirement": {
"requirement_type": "treatment necessity",
"expected_value": true
}
}
]
},
{
"exact_snippets": "history of immune related neurologic disease",
"criterion": "history of immune related neurologic disease",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "multiple sclerosis",
"criterion": "multiple sclerosis",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "autoimmune (demyelinating) neuropathy",
"criterion": "autoimmune (demyelinating) neuropathy",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "Guillain-Barre syndrome",
"criterion": "Guillain-Barre syndrome",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "myasthenia gravis",
"criterion": "myasthenia gravis",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "systemic autoimmune disease such as systemic lupus erythematosus (SLE)",
"criterion": "systemic lupus erythematosus (SLE)",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "connective tissue diseases",
"criterion": "connective tissue diseases",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "scleroderma",
"criterion": "scleroderma",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "inflammatory bowel disease (IBD)",
"criterion": "inflammatory bowel disease (IBD)",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "Crohn's",
"criterion": "Crohn's disease",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "ulcerative colitis",
"criterion": "ulcerative colitis",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "hepatitis",
"criterion": "hepatitis",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "history of toxic epidermal necrolysis (TEN)",
"criterion": "toxic epidermal necrolysis (TEN)",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "Stevens-Johnson syndrome",
"criterion": "Stevens-Johnson syndrome",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "phospholipid syndrome",
"criterion": "phospholipid syndrome",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
}
]
}
},
{
"identified_line": {
"line": "Healthy volunteers allowed",
"criterions": [
{
"exact_snippets": "Healthy volunteers allowed",
"criterion": "volunteer health status",
"requirement": {
"requirement_type": "status",
"expected_value": "healthy"
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "Healthy volunteers allowed",
"criterion": "volunteer health status",
"requirement": {
"requirement_type": "status",
"expected_value": "healthy"
}
}
]
}
},
{
"identified_line": {
"line": "Must have minimum age of 18 Years",
"criterions": [
{
"exact_snippets": "minimum age of 18 Years",
"criterion": "age",
"requirement": {
"requirement_type": "minimum",
"expected_value": {
"operator": ">=",
"value": 18,
"unit": "Years"
}
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"exact_snippets": "minimum age of 18 Years",
"criterion": "age",
"requirement": {
"requirement_type": "minimum",
"expected_value": {
"operator": ">=",
"value": 18,
"unit": "Years"
}
}
}
]
}
},
{
"identified_line": {
"line": "* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal (ULN) (or =< 5 x ULN for patients with liver metastases or Gilbert's disease)",
"criterions": [
{
"exact_snippets": "Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal (ULN)",
"criterion": "AST/ALT levels",
"requirement": {
"requirement_type": "comparison",
"expected_value": {
"operator": "<=",
"value": 3.0,
"unit": "x ULN"
}
}
},
{
"exact_snippets": "= < 5 x ULN for patients with liver metastases or Gilbert's disease",
"criterion": "AST/ALT levels for patients with liver metastases or Gilbert's disease",
"requirement": {
"requirement_type": "comparison",
"expected_value": {
"operator": "<=",
"value": 5,
"unit": "x ULN"
}
}
}
]
},
"logical_structure": {
"condition": {
"or_criteria": [
{
"exact_snippets": "for patients with liver metastases",
"criterion": "liver metastases",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "for patients with Gilbert's disease",
"criterion": "Gilbert's disease",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
},
"then_criteria": {
"exact_snippets": "= < 5 x ULN for patients with liver metastases or Gilbert's disease",
"criterion": "AST/ALT levels for patients with liver metastases or Gilbert's disease",
"requirement": {
"requirement_type": "comparison",
"expected_value": {
"operator": "<=",
"value": 5,
"unit": "x ULN"
}
}
},
"else_criteria": {
"exact_snippets": "Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal (ULN)",
"criterion": "AST/ALT levels",
"requirement": {
"requirement_type": "comparison",
"expected_value": {
"operator": "<=",
"value": 3.0,
"unit": "x ULN"
}
}
}
}
},
{
"identified_line": {
"line": "* The patient has no evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib. Patients with rectal tumor masses are not eligible",
"criterions": [
{
"exact_snippets": "no evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus)",
"criterion": "tumor invasion in GI tract",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "no evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib",
"criterion": "endotracheal or endobronchial tumor",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "Patients with rectal tumor masses are not eligible",
"criterion": "rectal tumor masses",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "no evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus)",
"criterion": "tumor invasion in GI tract",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "no evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib",
"criterion": "endotracheal or endobronchial tumor",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
{
"exact_snippets": "Patients with rectal tumor masses are not eligible",
"criterion": "rectal tumor masses",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
}
}
],
"exclusion_lines": [],
"miscellaneous_lines": [],
"failed_inclusion": [
{
"identified_line": {
"line": "* Renal Collecting Duct Carcinoma (Cohort K) - Per WHO definition (medullary involvement, predominant tubular morphology, desmoplastic stromal reaction, high grade cytology, infiltrative growth pattern, and absence of other renal cell carcinoma subtype or urothelial carcinoma)",
"criterions": [
{
"exact_snippets": "Renal Collecting Duct Carcinoma (Cohort K)",
"criterion": "Renal Collecting Duct Carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "medullary involvement",
"criterion": "medullary involvement",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "predominant tubular morphology",
"criterion": "tubular morphology",
"requirement": {
"requirement_type": "predominance",
"expected_value": true
}
},
{
"exact_snippets": "desmoplastic stromal reaction",
"criterion": "desmoplastic stromal reaction",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "high grade cytology",
"criterion": "cytology",
"requirement": {
"requirement_type": "grade",
"expected_value": "high"
}
},
{
"exact_snippets": "infiltrative growth pattern",
"criterion": "growth pattern",
"requirement": {
"requirement_type": "pattern",
"expected_value": "infiltrative"
}
},
{
"exact_snippets": "absence of other renal cell carcinoma subtype or urothelial carcinoma",
"criterion": "other renal cell carcinoma subtype or urothelial carcinoma",
"requirement": {
"requirement_type": "absence",
"expected_value": true
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Renal Collecting Duct Carcinoma (Cohort K)",
"criterion": "Renal Collecting Duct Carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "medullary involvement",
"criterion": "medullary involvement",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "predominant tubular morphology",
"criterion": "tubular morphology",
"requirement": {
"requirement_type": "predominance",
"expected_value": true
}
},
{
"exact_snippets": "desmoplastic stromal reaction",
"criterion": "desmoplastic stromal reaction",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "high grade cytology",
"criterion": "cytology",
"requirement": {
"requirement_type": "grade",
"expected_value": "high"
}
},
{
"exact_snippets": "infiltrative growth pattern",
"criterion": "growth pattern",
"requirement": {
"requirement_type": "pattern",
"expected_value": "infiltrative"
}
}
]
},
{
"not_criteria": {
"or_criteria": [
{
"exact_snippets": "absence of other renal cell carcinoma subtype or urothelial carcinoma",
"criterion": "other renal cell carcinoma subtype",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "absence of other renal cell carcinoma subtype or urothelial carcinoma",
"criterion": "urothelial carcinoma",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
]
}
}
]
}
},
{
"identified_line": {
"line": "* Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post menopause is defined as amenorrhea >= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason",
"criterions": [
{
"exact_snippets": "Women of childbearing potential include women who have experienced menarche",
"criterion": "menarche",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy)",
"criterion": "surgical sterilization",
"requirement": {
"requirement_type": "status",
"expected_value": false
}
},
{
"exact_snippets": "or are not postmenopausal",
"criterion": "postmenopausal status",
"requirement": {
"requirement_type": "status",
"expected_value": false
}
},
{
"exact_snippets": "Post menopause is defined as amenorrhea >= 12 consecutive months",
"criterion": "amenorrhea duration",
"requirement": {
"requirement_type": "duration",
"expected_value": {
"operator": ">=",
"value": 12,
"unit": "months"
}
}
},
{
"exact_snippets": "women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason",
"criterion": "amenorrhea cause",
"requirement": {
"requirement_type": "cause",
"expected_value": [
"prior chemotherapy",
"antiestrogens",
"ovarian suppression",
"any other reversible reason"
]
}
}
]
},
"logical_structure": {
"and_criteria": [
{
"and_criteria": [
{
"exact_snippets": "Women of childbearing potential include women who have experienced menarche",
"criterion": "menarche",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"not_criteria": {
"exact_snippets": "who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy)",
"criterion": "surgical sterilization",
"requirement": {
"requirement_type": "status",
"expected_value": true
}
}
},
{
"not_criteria": {
"exact_snippets": "or are not postmenopausal",
"criterion": "postmenopausal status",
"requirement": {
"requirement_type": "status",
"expected_value": true
}
}
}
]
},
{
"or_criteria": [
{
"not_criteria": {
"exact_snippets": "Post menopause is defined as amenorrhea >= 12 consecutive months",
"criterion": "amenorrhea duration",
"requirement": {
"requirement_type": "duration",
"expected_value": {
"operator": ">=",
"value": 12,
"unit": "months"
}
}
}
},
{
"exact_snippets": "women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason",
"criterion": "amenorrhea cause",
"requirement": {
"requirement_type": "cause",
"expected_value": [
"prior chemotherapy",
"antiestrogens",
"ovarian suppression",
"any other reversible reason"
]
}
}
]
}
]
}
},
{
"identified_line": {
"line": "* The patient has not experienced any of the following:",
"criterions": [
{
"exact_snippets": "The patient has not experienced any of the following",
"criterion": "experience of specific conditions",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
}
]
},
"logical_structure": {
"not_criteria": {
"exact_snippets": "The patient has not experienced any of the following",
"criterion": "experience of specific conditions",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
}
}
},
{
"identified_line": {
"line": "* Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening.",
"criterions": [
{
"exact_snippets": "Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe)",
"criterion": "congestive heart failure (CHF)",
"requirement": {
"requirement_type": "severity",
"expected_value": [
"New York Heart Association (NYHA) class III (moderate)",
"class IV (severe)"
]
}
}
]
},
"logical_structure": {
"or_criteria": [
{
"exact_snippets": "Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe)",
"criterion": "congestive heart failure (CHF)",
"requirement": {
"requirement_type": "severity",
"expected_value": "New York Heart Association (NYHA) class III (moderate)"
}
},
{
"exact_snippets": "Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe)",
"criterion": "congestive heart failure (CHF)",
"requirement": {
"requirement_type": "severity",
"expected_value": "class IV (severe)"
}
}
]
}
},
{
"identified_line": {
"line": "* Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment",
"criterions": [
{
"exact_snippets": "Concurrent uncontrolled hypertension",
"criterion": "uncontrolled hypertension",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "sustained blood pressure (BP) > 150 mm Hg systolic",
"criterion": "systolic blood pressure",
"requirement": {
"requirement_type": "value",
"expected_value": {
"operator": ">",
"value": 150,
"unit": "mm Hg"
}
}
},
{
"exact_snippets": "sustained blood pressure (BP) ... > 90 mm Hg diastolic",
"criterion": "diastolic blood pressure",
"requirement": {
"requirement_type": "value",
"expected_value": {
"operator": ">",
"value": 90,
"unit": "mm Hg"
}
}
},
{
"exact_snippets": "despite optimal antihypertensive treatment within 7 days of the first dose of study treatment",
"criterion": "antihypertensive treatment",
"requirement": {
"requirement_type": "effectiveness",
"expected_value": "ineffective"
}
}
]
},
"logical_structure": {
"exact_snippets": "failed",
"criterion": "failed",
"requirement": {
"requirement_type": "failed",
"expected_value": "failed"
}
}
}
],
"failed_exclusion": [],
"failed_miscellaneous": []
}