Metastatic and/or unresectable (cT4b) disease
Received radiotherapy to metastatic sites of disease <2 weeks prior to Day 1.
Progression of disease after 1 or 2 prior regimens in the metastatic setting
Definitive clinical or radiologic evidence of metastatic disease; required imaging studies must have been performed within 90 days prior to randomization
Clinical or radiographic evidence of metastatic disease; metastatic workup is not required, but is recommended for patients with clinical stage III disease; Note: isolated ipsilateral supraclavicular node involvement is permitted
Patients must have melanoma that is metastatic and clearly progressive on prior therapy
Definitive clinical or radiologic evidence of metastatic disease
No evidence of residual involved lymph node disease or metastatic disease at the time of registration based on clinician assessment of imaging; the treating physician will determine if incidental lesions on imaging require workup to exclude metastatic disease; if based on review of images, the treating physician determines the patient to be stage III, then the patient is eligible
Patients must not have metastatic disease (i.e., must be M0); patients must not have locally recurrent disease
Extent of disease:\r\n* Patients with non-metastatic and metastatic disease are eligible\r\n* Initially unresectable patients, with or without metastatic disease, are eligible as long as there is a commitment at enrollment to resect the primary tumor
Definitive clinical or radiologic evidence of metastatic disease
Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer
Patients must have measurable disease at baseline and 3 or fewer discrete, extracranial metastatic disease sites that are technically amenable to stereotactic body radiation therapy (SBRT) or resection (at least one disease site must be amenable to radiation); some examples of what constitutes specific radiation treatment sites defining distinct metastatic disease sites are as follows: a) A lesion in each adrenal gland represents 2 of 3 sites of metastatic disease allowed to be treated on protocol; b) Similarly to NRG study RTOG 0631, disease in 2 contiguous vertebral bodies (with up to 6 cm of paraspinal extension) can represent one site of disease in the spine; non-contiguous lesions in vertebral bodies separated by one vertebral body free of disease should be viewed as 2 sites of treatment; and c) Two lesions in such close proximity to one another that treatment with one isocenter is more accurate and safer in the liver, lungs, or other similar anatomic locations should be viewed as one site of metastatic disease treatment.
Patients with more than 3 discrete locations of extra-cranial metastatic disease after first-line systemic therapy requiring more than 3 radiation/surgery plans to cover these distinct metastatic disease entities.
Patients who have gross residual disease or distant metastatic disease
Prior palliative radiation treatment for metastatic disease to be treated on the protocol (including radiopharmaceuticals)
Definitive clinical or radiologic evidence of metastatic disease; no nodal involvement or evidence of metastatic disease allowed as defined by screening of the pelvis
Definitive evidence of metastatic meningioma
Known definitive clinical or radiologic evidence of metastatic disease
Metastatic disease that is not amenable to curative surgery or radiation
Presence of distant metastatic disease
Patients must have received irinotecan therapy in the metastatic setting; there are no limitation on number of prior therapies in the metastatic setting
Have histologically confirmed unresectable or metastatic nonsquamous NSCLC and having received no prior systemic therapy for metastatic disease.
Have a history of an invasive metastatic disease, except for the following:
Individuals with a history of invasive metastatic disease are eligible if they have been disease free for at least 2 years and are deemed by the Investigator to be at low risk for recurrence of that metastatic disease;
Presence of metastatic disease (stage IV NSCLC) is not allowed; subjects must be evaluated with a CT or PET scan prior to registration for protocol therapy to exclude metastatic disease
Has cSCC that is either metastatic defined as disseminated disease, and/or unresectable disease that is not curable by surgery, radiation, or systemic therapy.
Patients with distant metastatic disease
History of leptomeningeal metastatic disease
Patients who have received prior immunotherapy for unresectable or metastatic disease
Among patients with multiple sites of metastatic disease, the other sites that will not be treated on this protocol have either been previously treated or are planned for local treatment
For Part D dose confirmation: All participants must have histological evidence of cholangiocarcinoma and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. Participants must not have received >1 line of prior systemic therapy for metastatic or resectable disease (that is, participants may have received adjuvant gemcitabine and then later gemcitabine/cisplatin for recurrent metastatic disease).
SAFETY RUN-IN: Disease stage: unresectable metastatic disease
SAFETY RUN-IN: Patients received up to 2 prior regimens for their disease in the metastatic setting
Known spinal cord compromise or instrumentation due to metastatic disease. Radiation therapy for metastatic disease is allowed.
Symptomatic metastatic brain or meningeal tumors
Patients with evidence of metastatic disease involvement in viscera or bone
Have evidence of a distant metastatic disease
Patients may have had up to 3 prior regimens for metastatic disease
Metastatic CRPC
Prior treatment with nab-P for the treatment of metastatic disease.
Known metastatic disease
Patients are stage IV (M1) or recurrent with any combination of T and N with oligometastatic disease as defined by 5 or fewer total sites of metastatic disease \r\n* NOTE: number of metastatic sites based on most recent imaging studies in order to determine number of oligometastatic sites; for example, if patient initially had 10 sites of metastatic disease, was treated with chemotherapy resulting in complete response of 5 lesions and stable disease of 5 lesions, and no new lesions based on repeat imaging, the patient would be eligible for treatment on protocol
Metastatic disease sites must be treatable with SRS (at discretion of treating physician)
Examples of patients ineligible for trial\r\n* T1N1M1 NSCLC with 1 CNS lesion, 1 bone lesion, 1 adrenal lesion and a cervical lymph node (4 sites of metastatic disease)\r\n* T2N1M1 Gastric cancer with 6 liver lesions (more than 5 sites of metastatic disease)
Evidence or high suspicion of metastatic disease at enrollment
Unresectable or metastatic GIST
Definitive clinical or radiologic evidence of metastatic disease.
experienced disease progression during or after prior first-line regimen for metastatic disease
Progressed on or intolerant of at least 2 prior cancer therapy regimens administered for metastatic disease.
Participant has received more than one prior chemotherapy regimen for metastatic disease.
No evidence of extrahepatic metastatic disease
Pathologically confirmed squamous cell carcinoma of the head and neck with evidence of metastatic disease or locally recurrent disease considered incurable by local therapies; patients without pathologic or cytologic evidence of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation
Participants must have histologically or cytologically confirmed invasive breast cancer, with metastatic disease; participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation
Definitive clinical or radiologic evidence of metastatic disease, as documented by the treating institution
Metastatic non-small cell lung cancer (NSCLC), metastatic urothelial carcinoma or microsatellite instability high metastatic colorectal cancer (except for patients enrolling based on elevated TMB); For patients enrolling based on elevated TMB, patients with metastatic NSCLC, metastatic urothelial carcinoma or metastatic colorectal cancer will be allowed to enroll
Any patient with metastatic disease.
Presence of gliomatosis cerebri, cranial or spinal leptomeningeal metastatic disease
Pathologically proven, radiologic or clinical evidence of distant metastatic disease (this includes all disease below the clavicles, as well as disease metastatic to the bone, brain, or in the spinal canal)
Patient does not have metastatic disease
Patients may have received adjuvant chemotherapy and up to two prior chemotherapy for metastatic or locally recurrent disease; no prior nab-paclitaxel or mifepristone therapy for metastatic disease will be allowed
Before the first dose of study drug: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease; b) Has received other targeted or biological antineoplastic therapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic disease; c) Has had major surgery (<3 weeks prior to first dose).
Patient has evidence of metastatic disease
Willingness to undergo biopsy of metastatic site or site of unresectable disease prior to randomization
Evidence of measurable, locally recurrent or metastatic disease based on imaging studies within 28 days before the first dose of study drug.
No metastatic disease as per NCCN guidelines (www.nccn.org) - Bone scan indicated to r/o metastatic disease if clinical T1 and PSA > 20 or T2 and PSA > 10
The presence of extra capsular, seminal vesicle invasion or metastatic disease.
Metastatic melanoma eligible for {or currently o
Rapidly progressing multi-focal metastatic melanoma
Confirmed metastatic disease
Presence of gliomatosis cerebri, cranial or spinal leptomeningeal metastatic disease
Symptomatic metastatic brain or meningeal tumors
Symptomatic metastatic brain or meningeal tumors
PHASE IB: =< 2 lines of prior systemic therapy for metastatic disease (if patients have metastatic disease)
Patients with distant metastatic disease or otherwise not confined to the ipsilateral hemithorax
Initial diagnosis of metastatic disease must have occurred ?8 weeks prior to entry in the study.
Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
Evidence of metastatic disease
Patients must have a diagnosis of metastatic melanoma which is measurable either clinically or radiologically
Patients with a history metastatic melanoma involving the brain will be excluded if they have active disease or have had active disease within the prior six months that was not controlled with surgery or radiotherapy
Patients may not have metastatic disease, unless aged 2-10 with embryonal histology
No more than 3 lines of chemotherapy in the metastatic setting.
Patients with metastatic disease, including leptomeningeal or subarachnoid disseminated disease.
Has evidence of metastatic disease at time of diagnosis.
Cohort A: unresectable or metastatic melanoma
Cohort B: metastatic NSCLC
Has at least 2 identified sites of metastatic disease by imaging.
Patients who have had chemotherapy for metastatic castration-resistant prostate cancer within the past year (patients who have had docetaxel for metastatic castration sensitive per CHAARTED data may enroll as long as they did not have progressive disease while on docetaxel and are 6 months removed from treatment, with all treatment related toxicities resolving to at least grade 1)
Has distant metastatic disease on imaging or staging laparoscopy at the time of study entry
Participants must not have had prior systemic anticancer therapy for unresectable or metastatic melanoma
Diagnosis of metastatic disease
Presence of metastatic disease
Histopathologically confirmed diagnosis of metastatic NSCLC.
Recurrent/metastatic disease, fulfilling at least one of the criteria defined below:\r\n* Incurable disease as assessed by surgical or radiation oncology\r\n* Metastatic (M1) disease\r\n* Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity; patients who decline radical surgery are eligible
If Her2 positive, must have received and have progressed or are intolerant to treatment with trastuzumab for metastatic or recurrent disease
Total volume of metastatic disease more than 30 cm^3 excluding lesion to be resected
Presence of distant metastatic disease
Patients (both male and female) with advanced/metastatic GI cancers eligible for capecitabine monotherapy, including metastatic colorectal cancer, metastatic gastric and esophageal cancers, and unresectable or metastatic pancreatic cancer and cholangiocarcinoma, including gall bladder carcinoma, concurrent trastuzumab is allowed for HER2 positive gastric/esophageal cancer
Pathologic confirmation of respective malignancies; biopsy of metastatic disease is preferred but not mandatory
Patient has used capecitabine in a past regimen for metastatic disease
Has pre-existing brain or bone metastatic lesions.
Known metastatic disease
Metastatic disease
Other active non-melanoma metastatic cancers
Prior radiation treatment for metastatic disease
Presence of metastatic disease that can be biopsied by any methodology applicable
Has current or a history of any distant metastatic disease (including brain); an isolated or oligo-metastatic regional recurrence may be allowed if all other criteria are met, curative attempt is being pursued and if PI approval is granted
Evidence of metastatic disease
Distant metastatic disease of peritoneum: \r\n* Positive peritoneal cytology.\r\n* Carcinomatosis on diagnostic laparoscopy or laparotomy.
For patients with metastatic disease:
Has known metastatic disease as determined by conventional staging studies.
Participants must have histologically or cytologically confirmed invasive breast cancer, with metastatic disease; participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation
No evidence of metastatic disease as determined by imaging procedures.
Has pathologically confirmed metastatic pancreatic adenocarcinoma that has progressed after, at least, a first line of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed metastatic adenocarcinoma of the colon or rectum who have progressed to at least 2 lines of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed locally advanced or metastatic sqEC that has progressed after at least a first line of standard systemic therapy for metastatic disease. First-line participants can be enrolled if a platinum doublet is contraindicated or refused by the participants, OR pathologically confirmed locally advanced or metastatic sqNSCLC that has progressed after at least 2 lines of standard systemic therapy for metastatic disease.
Patients with either a confirmed diagnosis of (1) metastatic colorectal cancer in liver based on histopathology of either a prior resection of primary lesion or a biopsied liver metastatic lesion; (2) advanced HCC (BCLC-stage C) with a characteristic 3 or 4-phase CT or dynamic contrast enhanced MRI finding showing arterial uptake followed by \washout\ of contrast in the venous-delayed phases per American Association for the Study of Liver Disease (AASLD) criteria; (3) metastatic gastric cancer; (4) metastatic NSCLC without EGFR or ALK mutation.
Patients with distant metastatic disease (prostate adjacent adenopathy is not an exclusion)
Up to 3 prior chemotherapy regimens or metastatic disease
Patients must have had at least one line of therapy in the metastatic setting
DISEASE SPECIFIC EXPANSION COHORTS: Prostate cancers patients enrolled on this study must have:\r\n* Metastatic or advanced (incurable and unresectable) castration resistant metastatic cancer\r\n* Received at least one additional line of anti-androgen therapy with abiraterone or enzalutamide\r\n* Measurable disease is not required for enrollment
Both metastatic and inoperable primary-only patients are eligible
Both patients with stage IV and patients with recurrent disease after progression must have had at least 1 line of standard systemic therapy in the advanced/metastatic setting; a. patients with HER2-positive disease must have had at least 2 lines of anti-HER2 therapy, including Perjeta and Kadcyla in the metastatic setting; b. prior eribulin treatment is allowed
have metastatic disease evaluable on imaging studies;
Radiographic evidence of metastatic disease
Known metastatic disease
Patients must have metastatic or unresectable disease, including those with HER2+ disease
Previous treatment with cytotoxic chemotherapy therapy in the recurrent/metastatic setting; previous treatment with non-cytotoxic agents in the recurrent/metastatic setting is permitted
Patients with known leptomeningeal metastatic disease
Patients with extra-abdominal metastatic disease
More than 3 previous lines of therapy in the metastatic setting.
Any metastatic disease
Patients with metastatic disease are allowed, if indication to remove primary tumor
All patients must have progressed on at least one line of cytotoxic therapy for metastatic disease
Widely metastatic disease (oligometastatic disease acceptable)
The patient has three or less observable metastatic lesions. Metastatic lesions include distant M1 lymph node group; which will be counted as one site (M1 metastatic lymph nodes to include cervical, mediastinal, gastric, retroperitoneal lymph nodes will be counted as one lesion). Osseous metastases or visceral metastases will each count as one metastatic site. Each central nervous system (CNS) metastases will count as one metastatic site. Satellite lesions in the primary esophageal malignancy such as skipped esophageal primaries are not considered metastatic sites. Symptomatic metastatic sites can be treated locally prior to randomization or by palliative radiation
Metastatic disease.
Patients may have received one prior hormonal treatment for metastatic disease
Treatment for metastatic bladder cancer
Metastatic CRC
Evidence of metastatic disease.
Symptomatic metastatic brain or meningeal tumors
Patients must not have metastatic disease on staging work-up with blood cell count (CBC) and liver function studies
Clinically no evidence of local, regional, or metastatic disease at the time of study entry
Clinical or radiologic evidence of local or regional recurrence of disease or metastatic disease prior to or at the time of study entry
Metastatic RCC
Patients with metastatic disease, including leptomeningeal or subarachnoid disseminated disease
First line treatment for metastatic pancreatic cancer.
Metastatic disease or local-regional disease that is considered not resectable for cure
Has known metastatic disease; staging CT C/A/P or PET/CT will be mandatory no more than 45 days prior to enrollment to evaluate for the presence of metastatic disease
Has metastatic disease
Subjects must have previously untreated metastatic colorectal cancer and have no contraindications to treatment with the standard of care regimen as determined by the investigator; prior adjuvant therapy is acceptable (including immunotherapy), but must have been completed at least 6 months prior to metastatic disease diagnosis
Prior therapy to a metastatic site
Evidence of distant metastatic disease
Patients with more than >= 3 metastatic lung lesions or any one lesion greater than 5 cm and/or extensive metastatic disease outside the chest
Patient has had at least one prior systemic therapy for metastatic disease
The presence of metastatic pancreatic adenocarcinoma
Metastatic (stage IV) triple negative breast cancer that has progressed after at least one prior chemotherapy regimen in the metastatic setting; non-measurable disease (i.e. bone metastases) is permitted
Liver involvement by > 50% with metastatic disease determined by the investigator
Symptomatic metastatic brain or meningeal tumors
Cross-sectional imaging evidence of progression of recurrent/metastatic disease
Patients must have received 1 line of prior systemic therapy for metastatic or resectable disease (i.e. patients may have received adjuvant gemcitabine and then later gemcitabine/cisplatin for recurrent metastatic disease)
Clinically node negative, no evidence of metastatic disease
Has metastatic disease
Metastatic kidney cancer; clear cell histology component from primary or metastatic lesion
Radiographic evidence of metastatic disease
Evidence of metastatic disease that is extensive enough to preclude consideration of subsequent definitive surgery for the primary tumor
Metastatic
Histologic diagnosis of metastatic uveal melanoma.
Documented distant metastatic disease
Metastatic disease
Have a diagnosis of histologically confirmed metastatic colorectal cancer to the liver (no other sites of metastatic disease)\r\n* Histologic confirmation of a colorectal primary tumor is acceptable if accompanied by radiographic evidence of metastatic disease
Patients must not have known metastatic disease
One to 4 untreated metastatic brain lesions
Five or more metastatic brain lesions
Presence of metastatic disease or gross orbital involvement
Patients with metastatic disease will not be excluded
Patients with metastatic disease
MR imaging of the total spine (performed within 14 days of enrollment) demonstrates no evidence of spinal metastatic disease
All lines of prior therapy accepted; subjects with prior hepatic or extra-hepatic resections of metastatic disease will be included
Have had disease progression, been refractory or intolerant to no more than 2 prior systemic regimens for locally advanced or metastatic pancreatic cancer. Participants who have received prior neoadjuvant therapy and who now have metastatic disease must have received 1 of the following for their metastatic disease: FOLFIRINOX, nanoparticle albumin-bound paclitaxel/gemcitabine, TS-1 (tegafur gimeracil oteracil potassium), irinotecan liposome injection/5-fluorouracil (5FU)/Leucovorin or single-agent gemcitabine prior to enrolment in this study.
The subject has metastatic disease at the time of screening
Prior therapy to a metastatic site
Patients must have histologically confirmed diagnosis of melanoma; the pathologic confirmation may be from another metastatic site or from metastatic brain or spine lesions
No metastatic disease (M0)
Self-identified Black, African or African American women with proven diagnosis of advanced breast cancer (locoregionally recurrent or metastatic disease), either from the primary or a metastatic site
Patients must have received at least one prior therapy for metastatic disease to be eligible
Presence of extracranial metastatic or leptomeningeal disease
Patients with histologically confirmed metastatic melanoma, metastatic non-small cell lung cancer, metastatic breast cancer, or metastatic pancreatic adenocarcinoma relapsed or refractory to therapy as outlined below or patients with these malignancies who have declined, are or have become unable to tolerate (e.g. progressive chemotherapy-associated peripheral neuropathy), or were not eligible for standard therapy\r\n* Metastatic melanoma patients at any line of therapy\r\n* Metastatic non-small cell lung cancer patients who have relapsed or are refractory to at least one line of systemic anti-cancer therapy for metastatic disease, including cytotoxic chemotherapy or targeted therapy\r\n* Metastatic breast cancer patients who have relapsed or are refractory to at least one line of systemic anti-cancer therapy for metastatic disease, such as cytotoxic chemotherapy, hormonal therapy, or targeted therapy\r\n* Metastatic pancreatic adenocarcinoma who have relapsed or are refractory to at least one line of systemic anti-cancer therapy for metastatic disease, such as cytotoxic chemotherapy or targeted therapy
At least one prior regimen for treatment of recurrent or metastatic disease\r\n* Note: Prior regimen for recurrent or metastatic disease is not required if the patient had disease progression or recurrence during or within the first 6 months following completion of adjuvant or neoadjuvant chemotherapy
Symptomatic metastatic disease with signs of rapid progression per investigator’s clinical judgment
Patient is unable to have a biopsy of a metastatic site for Rb testing
Presence of metastatic disease on scans
Patient has stage N1 or M1 (metastatic) disease
Agree to participate in biopsy of metastatic lesion during the study at day 21
Patients on anticoagulation therapy which cannot be held for metastatic biopsies
Patients with documented HER2-positive metastatic disease based on most recent biopsy
Known metastatic disease
Metastatic or unresectable disease documented on diagnostic imaging studies
Metastatic disease outside of the liver
Inclusion criteria Part 1: Safety run-in\n\n          -  Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation\n\n          -  Aspartate transaminase (AST) < 2.5× ULN and Alanine transaminase (ALT) < 2.5× ULN\n\n          -  ECOG performance status ? 1\n\n        Part 2: Biomarker cohort\n\n          -  Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation\n\n          -  At least two cutaneous or subcutaneous or nodal lesions for tumor sample collection\n\n          -  ECOG performance status ? 2\n\n        Part 3: Double-blind, randomized, placebo-controlled part\n\n          -  Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation\n\n          -  ECOG performance status ? 2\n\n        Exclusion Criteria:\n\n        Part 1: Safety run-in\n\n          -  Subjects with uveal or mucosal melanoma\n\n          -  Any history of CNS metastases\n\n          -  Prior systemic anti-cancer treatment for unresectable or metastatic melanoma\n\n          -  Prior loco-regional treatment for unresectable or metastatic melanoma in the last 6\n             month\n\n          -  Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months\n\n          -  Radiation therapy within 4 weeks prior to start of study treatment\n\n          -  Active, known, suspected or a documented history of autoimmune disease\n\n        Parts 2 & 3: Biomarker cohort & double-blind, randomized, placebo-controlled part\n\n          -  Subjects with uveal or mucosal melanoma\n\n          -  Clinically active cerebral melanoma metastasis\n\n          -  Prior systemic anti-cancer treatment for unresectable or metastatic melanoma\n\n          -  Prior loco-regional treatment for unresectable or metastatic melanoma in the last 6\n             month\n\n          -  Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months\n\n          -  Radiation therapy within 4 weeks prior to start of study treatment\n\n          -  Active, known, suspected or a documented history of autoimmune disease\n\n        Other protocol-defined Inclusion/Exclusion may apply.
Known metastatic disease
Presence of overt metastatic disease at any site
Rapidly progressive symptomatic metastatic disease, as defined by the need for increased opioid analgesics within one month of registration for the treatment of pain attributed to a prostate cancer metastatic lesion; patients receiving opioids must receive approval from the principal investigator (PI) for eligibility
Untreated or metastatic pheochromocytoma
Presence of metastatic disease
Subjects with uncontrolled distantly metastatic disease per RECIST criteria (progressive disease) on imaging following chemotherapy
Known metastatic disease
Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective\r\n* Subject must have undergone at least 2 prior regimens for treatment of recurrent or metastatic disease
Patients with known synchronous distant metastatic disease
Multi-focal or metastatic disease
Multi-focal or metastatic disease (Arm B)
Evidence of metastatic disease
Known metastatic disease
No evidence of metastatic disease based on imaging of the chest, abdomen and pelvis
Metastatic disease on pretreatment imaging
Radiographical documentation of metastatic disease with imaging up to 6 weeks prior to enrollment
Definitive clinical or radiologic evidence of metastatic disease; imaging must have been performed no greater than 30 days prior to initiation of chemotherapy
Patient does NOT have known intracranial metastatic neuroblastoma; skull based disease with soft tissue extension is allowed
For patients undergoing definitive CFRT, patients with distant metastatic disease are not eligible
Progression or refractory disease to at least one regimen of therapy for metastatic disease in the breast and pancreatic cancer cohorts
Documented or pathologically-proven metastatic disease
Subjects with a diagnosis of metastatic disease who are currently receiving treatment or who have not been deemed in remission
Patients must have histological confirmation of metastatic cancer with at least one metastatic or primary lesion in the liver, lung, or adrenal gland
Patients must have had anti-HER2 based therapy for metastatic disease (which may include trastuzumab and pertuzumab either sequentially or in combination).
There must be documentation that the patient has evidence of measurable metastatic breast cancer. Histologic confirmation of metastatic disease is not required.
Distant metastatic disease
Known metastatic disease
Metastatic disease
Presence of distant metastatic (M1) disease
Presence of distant metastatic disease
Metastatic uveal melanoma
pT1-pT3pNxMx patients in whom standard National Comprehensive Cancer Network (NCCN) or American Urology Association (AUA) guidelines would suggest are at low risk for pelvic lymph node or metastatic disease and who would not require confirmatory imaging for metastatic disease; this includes patients with Gleason 6 or 7 (T2 disease) and prostate-specific antigen (PSA) less than 20
Metastatic colorectal cancer patients \r\n* Patient must have received a minimum of 1 systemic therapy in the metastatic setting
Metastatic pancreatic cancer
Patients with metastatic disease outside of the pelvis
History, presence, or suspicion of metastatic disease
Evidence of metastatic disease on imaging studies performed at the discretion of their physician
Patients must have had disease progression on or following their most recent treatment regimen or on presentation for the first time with metastatic disease
No evidence of distant metastatic disease
Metastatic pheochromocytoma
Step 1 subjects only: metastatic breast patients refractory to at least one standard therapy, with easily accessible metastatic deposits (cutaneous, subcutaneous, or superficial and/or palpable adenopathy/mass)
Presence of metastatic disease or gross (residual) orbital involvement
Patients with metastatic disease
Evidence of metastatic disease
No known local regional or distant metastatic disease
More than one prior chemotherapy line for metastatic disease
All patients must have histological proof of malignant cancer, which is metastatic; histological proof may be obtained from the primary tumor or another metastatic site; however, cytology alone is not an acceptable method of diagnosis
Untreated primary uveal melanoma except in cases where metastatic disease is diagnosed at the time of primary disease
Metastatic uveal melanoma patients with bone-only disease
Metastatic disease
Histologically-confirmed, mesothelin-expressing metastatic or advanced non-metastatic disease (tumour type specific inclusion criteria)
Presence of metastatic disease
No prior chemotherapy for metastatic disease
No evidence of metastatic disease
No clinical or radiological evidence of metastatic disease or local progression
Any evidence of metastatic disease
Received no more than 3 prior lines of systemic therapy for metastatic disease.
Histological or cytological diagnosis of metastatic CRC excluding known microsatellite instable sub-types, metastatic SCCHN or metastatic NSCLC that have progressed or have become intolerant to standard therapy, and whose disease may allow management with other available therapies
M0 stage based on no evidence of metastatic disease by CT imaging.
Presence of metastatic disease is not allowed; subjects must be evaluated with imaging consisting of CT scan and PET scan prior to enrollment for protocol therapy to exclude metastatic disease
Metastatic disease
Willing to undergo biopsy of a metastatic lesion at the time of progression
Patients with Gilbert's disease or known CNS metastatic disease.
Evidence of metastatic disease
Symptomatic metastatic brain or meningeal tumors
More than 3 metastatic tumors
Known history of metastatic brain or meningeal tumors.
Histologically confirmed adenocarcinoma of the breast with locally recurrent, unresectable disease or metastatic disease confirmed as described below; eligible patients include those with either:\r\n* De novo metastatic disease presenting without prior history of HER2-positive breast cancer:\r\n** Diagnosis should have been made from a biopsy of a metastatic disease site, but biopsy from the breast primary or involved regional lymph nodes is acceptable if biopsy of the metastatic sites was thought to carry excessive risk for the patient\r\n* Locally recurrent or metastatic disease following prior therapy for early breast cancer:\r\n** Diagnosis must have been made from the biopsy of the locally recurrent or metastatic disease\r\n** There must be an interval of >= 6 months between completion of neoadjuvant/adjuvant HER2-targeted therapy and documentation of locally recurrent or metastatic HER2-positive disease by biopsy
Patients with metastatic disease limited to the CNS
Metastatic disease
Other metastatic melanoma systemic disease allowed
Metastatic RCC
Metastatic disease or non-testicular primary
Patients with clinical evidence of metastatic disease.
Measurable metastatic disease (by RECIST version [v] 1.1) in the peritoneal cavity or retroperitoneal lymph nodes; disease outside of the peritoneal cavity is allowed as long as metastatic sites are also present within the peritoneum/retroperitoneum
Eligible for neutron radiation treatment to 1-3 sites of metastatic disease (lesions do not have to be symptomatic)
Patients must have refractory, recurrent or metastatic disease, which is deemed to be inoperable
Measurable metastatic uveal melanoma
Have received at least one prior therapy for metastatic disease
Presence of distant metastatic disease or disease not amenable to radiation treatment
Stable on, or responding to 1st line therapy for metastatic disease \r\n* At least 8 and not more than 16 weeks after initiating 1st line therapy for metastatic disease\r\n* Tumor stability/response on 1st line therapy will be determined as per RECIST 1.1
Metastatic pancreatic cancer based on imaging
Phase I only: Histologic confirmation of pancreatic, colorectal, gastroesophageal or biliary adenocarcinoma, as follows:\r\n* Patients with metastatic disease from pancreatic cancer who received no more than 2 lines of prior therapy in the metastatic setting\r\n* Patients with metastatic disease from colorectal cancer who received no more than 3 lines of prior therapy in the metastatic setting\r\n* Patients with metastatic disease from gastroesophageal cancer who received no more than 1 line of prior therapy in the metastatic setting\r\n* Patients with metastatic disease from biliary tract cancer who received no more than 1 line of prior therapy in the metastatic setting\r\n* NOTE: No prior exposure to irinotecan in the metastatic setting will be allowed except in the phase I dose escalation portion and in colon cancer patients only; in pancreas cancer, exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease < 3 months from last dose of irinotecan
Phase Ib only: Histologic confirmation of pancreatic or gastroesophageal adenocarcinoma, as follows:\r\n* Patients with metastatic disease from pancreatic cancer who received no more than 1 line of prior therapy in the metastatic setting\r\n* Patients with metastatic disease from gastroesophageal cancer who received no more than 1 line of prior therapy in the metastatic setting\r\n* NOTE: No prior exposure to any irinotecan in the metastatic setting will be allowed
Presence of metastatic disease
Pancreatic cancer cohort specific criteria:\r\n* Patients must have unresectable or metastatic pancreatic cancer\r\n* Patients must have failed at least one prior line of therapy for metastatic or unresectable disease or have recurred within 6 months of completing adjuvant chemotherapy\r\n* Patients with liver metastases must have < 50% involvement of the liver
Histologic diagnosis of metastatic melanoma
Any prior systemic treatment for metastatic colorectal cancer
No evidence of distant metastatic disease
Metastatic or inoperable urothelial cancer
Diagnosis of metastatic disease
Patients with evidence of metastatic disease involvement in viscera or bone
Radiographic evidence of metastatic disease
Patients with metastatic disease
Definitive clinical or radiologic evidence of metastatic disease
Evidence of distant metastatic disease (i.e. lung, liver, bone, brain, etc.)
Have localized pancreatic ductal adenocarcinoma (PDA)s at the time of original diagnosis without any definitive evidence of distant metastatic disease
Cohort 2 (MTD) only: metastatic adenocarcinoma of the pancreas; prior systemic treatment for metastatic disease is allowed
No evidence of metastatic disease by clinical and radiological staging
Patients with metastatic disease beyond the neck and supraclavicular region will be excluded
At least one prior systematic therapy in the metastatic setting
Evidence or suspicion of disease metastatic to sites remote from the supratentorial brain
COHORT II (MTD): metastatic adenocarcinoma of the pancreas and tumor amenable to biopsies; prior systemic treatment for metastatic disease is allowed
The subject must have progressive disease following at least one prior line of hormonal or chemotherapy for treatment of their metastatic disease
For metastatic disease to lung, primary tumor needs to be controlled (no evidence of progression on imaging for at least 2 months)
Metastatic disease by bone scan
Patients must have no evidence of metastatic disease; metastatic disease:\r\n* Are lesions which are discontinuous from the primary tumor, are not regional lymph nodes and do not share a body cavity with the primary tumor; if there is any doubt whether lesions are metastatic, a biopsy of those lesions should be taken\r\n* Skeletal lesions in adjacent bones (trans-articular)\r\n* Contralateral pleural effusion and contralateral pleural nodules\r\n* Distant lymph node involvement\r\n* Patients with pulmonary nodules are considered to have metastatic disease if the patient has:\r\n** Solitary nodule > 0.5 cm or multiple nodules of > 0.3 cm unless biopsied and negative for Ewing's\r\n** Biopsies of solitary nodule =< 0.5 cm or multiple nodules =< 0.3 cm are not required but if performed and positive indicate metastatic disease
Symptomatic metastatic brain or meningeal tumors
Have stable metastatic pancreatic cancer after receiving 8-12 doses of FOLFIRINOX (measurable disease is not required)
Patients who have had prior chemotherapy for metastatic pancreatic cancer (other than FOLFIRINOX); prior radiation is allowed; chemotherapy for non-metastatic disease is allowed
Patients must have metastatic disease
Patient has known nodal or distant metastatic disease; patients with nodal or metastatic disease require systemic chemotherapy; furthermore, they should be excluded from this clinical trial because of their poor overall prognosis
Patients are allowed (but not required) to have up to two lines of prior chemotherapy regimens for metastatic disease
Patients must have received at least 1 chemotherapy regimens in the setting of metastatic disease
IV bisphosphonate and denosumab for bony metastatic disease will be allowed
Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles
Patients must have pathologically or radiologically confirmed metastatic disease in the brain
Have not been treated with gemcitabine in the metastatic setting
Chest x-ray negative for metastatic disease
Definitive clinical or radiologic evidence of metastatic disease; (chest imaging [mandatory for all patients] and other imaging [if required] must have been performed within 90 days prior to randomization)
Patients with metastatic disease must have received at least one line of standard of care (SOC) treatment for metastatic disease prior to enrollment
Patients with distant metastatic disease (stage IVC)
Measurable metastatic ocular melanoma
Radiological evidence of metastatic disease
Patients with evidence of metastatic disease outside of the pelvis
Patients may be treatment-naive or may have been previously treated for metastatic disease
Evidence of metastatic disease outside of the abdomen
Evidence of metastatic disease outside of the abdomen
First or second line chemotherapy treatment for metastatic disease
Patients have locally recurrent or distant relapsed metastatic disease
Phase I: Patients must have received at least one prior chemotherapy regimen for metastatic disease; patients with deleterious germ line mutations in breast cancer (BRCA)1 or BRCA2 are not required to have received prior chemotherapy for metastatic disease
Up to four prior chemotherapy regimens and anti-HER2 agents in the metastatic setting allowed; patients must have progressed on trastuzumab based therapy and must have received ado-trastuzumab emtansine for metastatic breast cancer
One to ten brain metastatic lesions
Previous radiosurgery to any currently progressive gross metastatic disease
Be receiving first-line therapy for metastatic disease
Patients may have received chemotherapy as a component of their primary tumor treatment but not for recurrent or metastatic disease
Current or previous evidence of muscle invasive (muscularis propria) or metastatic disease presented at the screening visit. Examples that increase the risk of metastatic disease are (but not limited to):
Patient with documented evidence of metastatic disease
Subjects enrolled into the C3 Cohort must have not had treatment for their metastatic disease
At least one prior regimen of chemotherapy in the setting of metastatic breast cancer; no upper limit on the number of prior endocrine regimens for metastatic breast cancer, however no more than 6 chemotherapeutic regimens may have been given in the metastatic setting
Widespread (metastatic) disease, or returned after previous treatment (recurrent)
Previous treatment for metastatic or recurrent disease
Received prior trastuzumab or chemotherapy for metastatic breast cancer except if patient has CNS as only site of metastatic disease
Subjects must have recurrent/metastatic disease and may have been previously treated in the recurrent/metastatic setting.
Disease progression after crizotinib only. No prior chemotherapy is allowed in the metastatic disease setting.
Disease progression after crizotinib and 1 or 2 prior regimens of chemotherapy in the metastatic disease setting.
Have received more than one prior systemic chemotherapy regimen for metastatic disease.
Clinical and radiologic assessments that are negative for local or regional recurrence of disease or metastatic disease at the time of study entry, including
Clinical or radiologic evidence of local or regional recurrence of disease or metastatic disease prior to or at the time of study entry
Intravenous (IV) bisphosphonate and denosumab for bony metastatic disease will be allowed
Prior or present evidence of distant metastatic disease as assessed by radiographic imaging;
is unresectable or metastatic
Disease progression during or within 6 months after treatment with one line of 5-Fluorouracil (5-FU)- or gemcitabine-based chemotherapy in the metastatic setting
Subjects with recurrent (unresectable) or metastatic CRC:
Evidence of distant metastatic disease
Patients with known HER-2 overexpressing MBC must have failed at least one prior trastuzumab-containing regimen for metastatic disease.
Confirmed recurrent or metastatic disease
Patients must have had one and only one prior regimen of systemic therapy for metastatic disease unless the patient meets the criteria below
Metastatic disease or incurable locally recurrent disease
Prior systemic therapy for metastatic or recurrent NSCLC.
History of metastatic disease at any time or presence of detectable metastases.
Patients with chemotherapy for metastatic disease (patients with 0-3 prior lines of chemotherapy for metastatic breast cancer [MBC])
No prior or present evidence of metastatic disease;
No prior cytotoxic chemotherapy to treat their metastatic disease
Evidence of distant metastatic disease (Masaoka stage IVB)
Definitive clinical or radiological evidence of metastatic disease
More than 3 prior regimens for metastatic RCC.
No prior systemic chemotherapy for recurrent or metastatic disease
Metastatic disease involving bone with metastatic disease previously confirmed by prior biopsy; or Metastatic disease involving bone previously confirmed on imaging (e.g. CT or MRI) with known (biopsied) primary disease (primary bone cancer is excluded)
Pain must be from one painful metastatic lesion involving the bone that is amenable to cryoablation with CT (additional less painful metastatic sites may be present)
Inclusion Criteria:\n\n          -  Must have cancer of the anal canal OR rectal cancer.\n\n          -  Must have metastatic disease or persistent/recurrent loco-regional disease\n\n          -  Prior Therapy: may have received <2 regimens for disease in the metastatic setting. At\n             least one line of therapy.\n\n          -  Be willing and able to provide written informed consent for the trial.\n\n          -  Be ?18 years of age on day of signing informed consent.\n\n          -  Have measurable disease based on RECIST 1.1\n\n          -  Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n\n          -  Demonstrate adequate organ function as defined in protocol.\n\n          -  Females cannot be pregnant or breastfeeding and must take two methods of birth control
Patient must have received no prior radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease.
Known untreated or unstable CNS metastatic disease.
Symptomatic metastatic brain or meningeal tumors
Presence of metastatic disease that, in the opinion of investigators, would require palliative treatment within 4 weeks of enrollment
Evidence of metastatic disease or nodal disease outside the prostate on bone scan or cross-sectional imaging.
Randomized Phase 2 Dose Expansion - Individuals may have disease progression during treatment or within 12 months of completion of endocrine therapy (tamoxifen, and/or AI) in the adjuvant setting, or disease progression during treatment with endocrine therapy (tamoxifen, AI or CDK4/6 inhibitor plus AI) for advanced/metastatic disease. Individuals may have had unlimited prior hormonal therapy, but must be naive to fulvestrant in the metastatic setting. A total of 2 prior chemotherapies are allowed, however, only one for metastatic disease is permitted.
Prior systemic therapy for metastatic disease
Subject has not been treated by systemic anticancer therapy for unresectable or metastatic melanoma
Previous chemotherapy for recurrent or metastatic disease.
Adult Asian women with locoregionally recurrent or metastatic disease not amenable to curative therapy
Have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease
Metastatic breast cancer (MBC) OR metastatic non-small cell lung cancer (NSCLC) OR metastatic adenocarcinoma of the prostate; the sites of allowed metastases are: peripheral lung, central lung, mediastinal/cervical lymph node, liver, spinal/paraspinal, osseous, and abdominal-pelvic\r\n* NOTE: after the required number of evaluable patients have been accrued for a given dose level, the accrual for that metastatic location will be temporarily suspended while the safety of that dose level is assessed; a patient can only be entered onto the trial if all of their metastatic locations are open to accrual (e.g. if central lung is temporarily suspended for safety assessment and the patient has a central lung metastases, regardless of other metastases, they cannot enroll until the safety of dose to central lung is determined)
Patients may not be receiving concurrent chemotherapy for treatment of metastatic disease
Histologic diagnosis of unresectable or metastatic melanoma; for unknown primary disease, diagnosis of metastatic disease by cytology fine-needle aspiration (FNA) is not acceptable; BRAF wild-type confirmed, and NRAS mutation assessed
RCC subjects must have received ?1 prior line of therapy for metastatic disease (Part 1A)
Subjects must have experienced disease progression or recurrence during or after at least one systemic therapy for advanced or metastatic disease
Documented distant metastatic disease; NOTE: pelvic lymphadenopathy is NOT excluded
Patients must have measurable metastatic melanoma
Evidence of metastatic disease on cross sectional imaging or bone scan
Adult women with locoregionally recurrent or metastatic disease not amenable to curative therapy.
Documented distant metastatic disease
METASTATIC SAFETY COHORT
The patient must have received no more than 3 prior lines of therapy for metastatic disease.
The patient must have received no more than 2 prior lines of therapy for metastatic disease.
Have histologically confirmed unresectable or metastatic melanoma having received no more than one prior systemic therapy for the metastatic disease (eg. ipilumamab and/or BRAF inhibitor); unresectable or metastatic smoking-associated NSCLC having received no more than one prior systemic therapy for the metastatic disease (eg standard of care chemotherapy, as appropriate); unresectable or metastatic transitional cell carcinoma of the bladder, urethra, ureter or renal pelvis having received no more than one prior systemic therapy for the metastatic disease.
Clinical or radiographic evidence of metastatic disease; metastatic workup is not required\r\n* Note: isolated ipsilateral supraclavicular node involvement is permitted
Histologic diagnosis of unresectable or metastatic BRAF V600 mutant melanoma
Patients must have disease that is not amenable to potentially curative resection, and must not have metastatic disease
Resectable, borderline resectable or metastatic disease
Progression after at least first-line systemic therapy for metastatic disease
Patients must have recurrent and/or metastatic disease not amenable to potentially curative surgery or radiotherapy
Symptomatic metastatic brain or leptomeningeal tumors (asymptomatic or treated metastatic brain or leptomeningeal tumors are allowed)
No more than 4 prior chemotherapeutic regimens for metastatic disease
Biopsy proven breast carcinoma which is persistent and metastatic or recurrent and metastatic.
Patients must have failed at least one line of chemotherapy for metastatic disease.
Definite evidence of metastatic disease
Any distant metastatic disease
Have histologically or cytologically diagnosed oligo-metastatic prostate cancer; oligo-metastatic disease is defined to reflect men with low volume disease; specifically, oligo-metastatic disease is defined as less than 5 extra-pelvic metastases; metastatic lesions may be lymph nodes
Cohort 2 patients must have had a complete resection of all sites of metastatic disease within 30 days prior to enrollment\r\n* Patients will only be eligible after they have undergone complete surgical resection of suspected metastatic disease that is histopathologically confirmed to be osteosarcoma prior to enrollment\r\n** Note: the definition of complete resections is: gross resection of all disease as per the operating surgeon; post-operative imaging is not required for confirmation of complete resection\r\n* Patients must undergo resection of any lung lesion meeting criteria for likely metastatic disease, defined as: \r\n** 3 or more lesions > 5 mm in diameter OR a single lesion > 1 cm\r\n* Patients with lung as the only site of resected metastatic disease must have refused participation in protocol AOST1421\r\n** Note: this applies if AOST1421 is open to enrollment at the enrolling institution on the day the patient consents
Evidence of metastatic disease
Known metastatic disease
Metastatic disease
Symptomatic metastatic brain or meningeal tumors
Metastatic or recurrent CRC
Metastatic or unresectable disease documented on diagnostic imaging studies
Visceral (eg, lung, liver) metastatic disease. Adenopathy is allowed;
Have histological or cytological evidence of colorectal adenocarcinoma with confirmation of metastatic disease either by pathologic or radiologic findings.
Have had no prior systemic therapy for advanced or metastatic disease. Prior adjuvant therapy should have been completed at least 9 months from documentation of metastatic disease. Prior palliative radiotherapy allowed if toxicities resolved to grade 1 or baseline.
Phase Ib dose escalation cohort study: subjects with histologically assessed metastatic clear cell RCC (defined as more than 50% clear cell component) after failure of at least one systemic therapy for metastatic disease (including, but not limited to prior therapy with interleukin 2, interferon, bevacizumab, VEGF TKI, and mTOR) for metastatic disease. NOTE: A biopsy to prove metastatic disease is not required.
Phase II study: subjects with treatment-naïve histologically assessed metastatic clear cell RCC (defined as more than 50% clear cell component) and who are candidates for standard first-line therapy. NOTE: A biopsy to prove metastatic disease is not required.
Presence of metastatic disease (stage IV NSCLC) is not allowed. Subjects must be evaluated with a PET scan within 28 days prior to registration for protocol therapy to exclude metastatic disease
Received more than 1 regimen for recurrent or metastatic disease
Patients must have been treated with at least one prior systemic treatment for incurable advanced or metastatic SCCA of the anal canal; prior treatment for metastatic disease is not required for patients who develop new metastatic lesions during or within 6 months of completion of chemoradiation for limited-stage disease; patients who receive chemotherapy for incurable advanced or metastatic SCCA of the anal canal must wait a minimum >= 28 days (6 weeks for nitrosoureas or mitomycin C) after the date of completion of chemotherapy prior to initiating treatment with nivolumab on this study; patients who undergo radiotherapy to a site of tumor must wait a minimum >= 3 months from the date of completion of radiotherapy prior to initiating treatment with nivolumab on this study
Patients must have histologically proven metastatic non-small cell lung cancer (stage IV disease or recurrent metastatic disease, according to the 7th edition of the lung cancer tumor, nodes, metastasis [TNM] classification system) (for cohort A), or histologically proven metastatic small cell lung cancer (extensive stage or recurrent metastatic disease) for cohort B; (patients with tumors having mixed small cell and non-small cell elements may be enrolled on cohort B), or females with histologically or cytologically confirmed carcinoma of the breast (either the primary or metastatic lesions) for whom single-agent cytotoxic chemotherapy is indicated
Have metastatic disease
Has a metastatic deposit that can be biopsied
Definitive clinical or radiologic evidence of metastatic disease.
Treatment with bevacizumab in at least one prior line of therapy for metastatic disease
Metastatic disease
Recurrent/metastatic disease, fulfilling at least one of the criteria defined below:\r\n* Incurable disease as assessed by surgical or radiation oncology\r\n* Metastatic (M1) disease\r\n* Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity; patients who decline radical surgery are eligible
Use of a systemic treatment regimen for metastatic disease within 28 days preceding the first dose of AEB071 and BYL719
Previously treated with 3 or more systemic regimens given for recurrent and/or metastatic disease
Have metastatic disease
Have received and failed only 1 prior chemotherapy regimen for metastatic pancreatic cancer\r\n* Must have received and failed only 1 prior regimen administered for pancreatic cancer in the metastatic setting; failure includes development of metastases on or within 3 months of adjuvant chemotherapy treatment or development of metastases on or within 3 months of treatment for locally advanced disease or radiographic disease progression on or within 3 months of treatments for metastatic disease; documented intolerance (grade 3 or 4 toxicity or hospitalization leading to discontinuation) of treatment for metastatic disease will also be considered a failure\r\n* Radiosensitizing doses of chemotherapy are not considered systemic chemotherapy
Presence of metastatic or recurrent disease
Have recurrent or metastatic solid tumors
Documented radiological disease progression during the most recent treatment regimen for metastatic disease
Most recent treatment regimen for metastatic disease must include Trastuzumab and chemotherapy.
Last treatment for metastatic disease including Trastuzumab in combination with pertuzumab
Received more than 1 systematic palliative regimen for recurrent or metastatic disease
Patients with metastatic pancreatic adenocarcinoma not treated with chemotherapy for metastatic disease
Subject may have received ?2 prior regimens for the treatment of their metastatic disease.
No more than 2 prior courses of systemic therapy for metastatic melanoma
For patients with metastatic melanoma not of uveal origin, v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation determination using a Clinical Laboratory Improvement Amendments (CLIA)-approved testing method on metastatic tumor tissue\r\n* NOTE: patients with metastatic melanoma of uveal origin do not need to have formal BRAF testing due to low probability of a BRAF V600 mutation in their metastatic tumor
Patients with metastatic cancer
Patients with distant metastatic disease (M1c) will not be eligible for this study
Documentation of metastatic disease
At least 2 and no more than 3 prior lines of therapy for incurable or metastatic NSCLC
Symptomatic metastatic brain or meningeal tumors
1-3 sites of metastatic disease able to be targeted by SABR
presented de novo with metastatic disease and then relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as first line endocrine therapy for metastatic disease. Participants may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease
Patients must have recurrent and/or metastatic disease not amenable to potentially curative surgery or radiotherapy
Symptomatic metastatic brain or meningeal tumors (asymptomatic or treated metastatic brain and leptomeningeal tumors are allowed)
Distant metastatic disease not limited to peritoneum: solid organ metastases (liver, central nervous system, lung)
Any distant metastatic disease visualized on preoperative imaging:\r\n* Solid organ metastases\r\n* Clear radiologic evidence of carcinomatosis
Have hormone-sensitive metastatic disease (M1) as evidenced by soft tissue and/or bony metastases
Prior chemotherapy for metastatic disease
Evidence of metastatic disease
Metastatic disease
Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic disease
COHORT B: Visceral metastatic disease
Presence of extracranial metastatic or leptomeningeal disease
No prior chemotherapy for metastatic disease
Prior systemic chemotherapy for metastatic disease
Evidence of metastatic disease (stage M1)
Imaging confirmation of metastatic disease
Patients must not have evidence of metastatic tumor or other cancer
Patient presents with Stage 4 pulmonary metastatic disease with metastatic disease previously confirmed by prior biopsy; or Patient presents with Stage 4 pulmonary metastatic disease previously confirmed on imaging (e.g. computerized tomography or CT) with histology proven primary cancer.
Patient has uncontrollable primary or metastatic disease outside of the lung.
Prior disease progression on docetaxel or paclitaxel in metastatic setting
Metastatic brain or leptomeningeal tumors (treated metastatic brain or leptomeningeal tumors are allowed)
Patients with metastatic sites that requires chemotherapy
Group B:\r\n* Newly diagnosed patient with histologically proven Ewing sarcoma family of tumor involving the bone or soft tissue and at least one of the following:\r\n** Metastatic disease (must be biopsy proven)\r\n** Pelvic primary\r\n** Age >= 14 years at the time of diagnosis\r\n*** Patients with more than one pulmonary lesion > 1cm may be considered as having evidence of metastatic disease without biopsy, as long as there is no other clear medical reason for these lesions; these cases should be discussed with the principal investigator (PI) and if there is any doubt, a biopsy should be obtained\r\n* Newly diagnosed patients with intra-abdominal, unresectable or metastatic desmoplastic small round cell tumor; metastatic site must be biopsy proven
Radiographic evidence of metastatic disease; evaluable non-target lesions and/or bone only metastasis are permitted
Patients with rapidly progressive or extensive symptomatic visceral metastatic disease
Histological or cytological documentation of solid tumors for whom single agent irinotecan is recommended; biopsy of primary tumor alone is adequate if the patient has clear evidence of metastatic disease and/or elevated carcinoembryonic antigen (CEA) and the treating physician does not feel biopsy of metastatic disease is clinically warranted
No previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
Non metastatic pancreatic ductal adenocarcinoma
Locoregionally recurrent or metastatic disease that has not previously been treated with systemic therapy of recurrent or metastatic disease
Prior treatment with any chemotherapy for metastatic disease from pancreatic cancer
Patients with metastatic uveal melanoma
Evidence of metastatic disease with measurable lesion(s) as defined by RECIST guideline version 1.1 to permit tumor response evaluation; subjects with unresected primary tumors may be enrolled as long as evidence of measurable metastatic disease is also present
Documented, progressive disease/tumor growth, which may include after exposure to a platinating agent (e.g. cisplatin or carboplatin) or another cytotoxic chemotherapy or radiation in a prior line of therapy, or documented intolerance to such an agent; prior line of therapy may include induction chemotherapy or chemoradiotherapy, in addition to treatment for recurrent/metastatic disease; de novo metastatic disease is also allowed as long as progressive disease/evidence of tumor growth is documented
Radiographic evidence of metastatic disease, detectable by bone scan, CT scan, or MRI. At least one site of metastatic disease must be amenable to needle biopsy.
Patients with ER and/or PR- positive/ HER2 non-amplified invasive mammary carcinoma must have had at least one line of endocrine therapy in the metastatic setting, or be diagnosed with metastatic breast cancer during or within 1 year of adjuvant endocrine therapy; there is no limit on lines of prior treatment in the metastatic setting
Patients with ER and/or PR-positive/ HER2-amplified invasive mammary carcinoma must have had at least one line of HER2-targeted therapy in the metastatic setting, or be diagnosed with metastatic breast cancer during or within 1 year of adjuvant HER2-targeted therapy; there is no limit on lines of prior HER2-targeted treatments in the metastatic setting
Patients with metastatic or advanced-stage malignant tumor. Patients may have received up to 2 prior lines of chemotherapy for their metastatic disease
Metastatic colorectal cancer
Patients must have metastatic disease of the esophagus, gastroesophageal junction or stomach; patients with locally recurrent disease who are not deemed eligible for radiation are also permitted\r\n* Histological, cytologic or radiographic documentation of metastatic adenocarcinoma or squamous cell carcinoma of the esophagus, gastroesophageal junction or stomach; radiologic, endoscopic, histologic or cytologic evidence of locally recurrent disease is also permitted
Symptomatic metastatic disease, as defined by the need for opioid analgesics for the treatment of pain attributed to a prostate cancer metastatic lesion; patients receiving opioids must receive approval from the principal investigator (PI) for eligibility
Patient must not have known distant metastatic disease at presentation
Evidence of distant metastatic disease.
Presence of gliomatosis cerebri, cranial or spinal leptomeningeal metastatic disease
At least one prior treatment for metastatic disease
Metastatic disease for stratum B only
Any metastatic disease
Patients with clinical, radiological/laboratory, or pathological evidence of distant metastatic disease
Patients must have metastatic or unresectable disease
Patients with prior surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless an interval of > 5 years has elapsed between the primary surgery and the development of metastatic disease; clinicians should consider biopsy of lesions to establish diagnosis of metastatic disease if there is substantial clinical ambiguity regarding the nature or source of apparent metastases
Patients with a history of colorectal cancer treated by surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless:\r\n* Either an interval of > 5 years has elapsed between the primary surgery and the development of metastatic disease, OR\r\n* The primary cancer was stage I\r\nClinicians should consider biopsy of lesions to establish the diagnosis of metastatic colorectal cancer in each case if there is substantial clinical ambiguity regarding the nature or source of apparent metastases
Metastatic Pancreatic Cancer
Patients must have histologically or cytologically confirmed invasive breast cancer, with metastatic disease; patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis by physical exam or radiologic study
Measurable metastatic melanoma with available autologous TIL
Patient has known metastatic disease
Uveal melanoma with biopsy proven metastatic disease
More than three prior lines of cytotoxic chemotherapy for metastatic disease
Women with metastatic disease outside of pelvis
No evidence of extranodal metastatic disease
I 02. Metastatic disease.
Patients with breast cancer must have had at least one prior chemotherapy regimen for metastatic disease; additionally, patients with breast cancer must have received prior tamoxifen and/or aromatase inhibitor therapy (if post-menopausal) with at least one hormonal regimen in the metastatic setting; patients with HER2+ breast cancer must have progressed after at least one prior HER2-directed regimen (trastuzumab, lapatinib) for metastatic disease\r\n* All other patients must have disease that has progressed following at least one line of standard therapy; prior therapy with tamoxifen is allowed
Patients should have at least one organ system involved with distant metastatic disease; if only a single metastatic lesion is present, biopsy is mandatory
If patient has only one metastatic lesion/focus, this must be proven by biopsy and the pathology report confirming the diagnosis of primary breast cancer, as well as the metastatic site, must be available
Patients with newly diagnosed stage IV NSCLC with an untreated primary must have no more than 3 active extracranial metastatic lesions other than the primary site and regional lymph nodes\r\n* Patients with metastatic disease treated by local therapy at the time of registration but untreated thoracic disease will be included
OTHER METASTATIC SITES:
Definitive clinical or radiologic evidence of metastatic disease; indeterminant lung nodules less than 8 mm are acceptable
Patients must have recurrent and/or metastatic disease not amenable to potentially curative surgery or radiotherapy
Symptomatic metastatic brain or leptomeningeal tumors (asymptomatic or treated metastatic brain or leptomeningeal tumors are allowed)
Expansion Cohort 6: Subjects with metastatic CRPC (adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features) who have radiographically progressed in soft tissue on or after enzalutamide and/or abiraterone acetate for metastatic disease.
Patients with metastatic disease
Resectable primary tumor with no evidence of metastatic disease by imaging. Imaging must be performed within 45 days of Day 1 of study.
Patients who have received more than one chemotherapy regimen for metastatic disease
CT or MRI evidence of metastatic disease to the bone
Presence of extra-cranial metastatic disease
Prior palliative chemotherapy for metastatic or recurrent disease
Prior biological therapy for metastatic or recurrent disease within 3 weeks prior to randomization
Patients who have metastatic disease, if the metastatic sites are amendable for local therapy (i.e. radiation and/or surgery), and are candidates for breast surgery will be eligible
At least 2 biopsiable easily accessible cutaneous and subcutaneous lesions in patients in the metastatic disease cohort
1 to 3 bone metastatic sites (metastatic lesions in the same bone that are within 3 cm of each other are considered as one site)
At least 1 prior antineoplastic chemotherapy treatment regimen for metastatic disease and at least 1 prior treatment with a trastuzumab-containing regimen for at least 6 weeks, for metastatic disease or subject relapsing under adjuvant treatment (part 2 only).
More than 2 prior antineoplastic treatment regimens (excluding hormonotherapy) for metastatic disease. Subjects who relapsed under adjuvant treatment shouldn't have received more than one line of chemotherapy for metastatic disease (part 2 only).
Group A: Metastatic disease, myeloma, lymphoma;
Patient must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
Metastatic brain or meningeal tumors (symptomatic or asymptomatic).
No prior systemic therapy for metastatic disease.
Definitive clinical or radiologic evidence of metastatic disease; pN3 disease is not allowed (positive common iliac node)
Prior or current evidence of any metastatic involvement of any distant site
Progressive metastatic (M1) disease on androgen deprivation therapy
Patients with metastatic disease
Patients may undergo an optional biopsy of the metastatic disease at baseline and after 2 cycles of BIBF-1120
Have received at least one any prior treatment for local recurrence or metastatic disease and have relapsed
Patients with only locally or regionally confined disease without evidence of metastatic disease
Symptomatic metastatic brain or meningeal tumors
More than 2 prior cytotoxic chemotherapy regimens for relapsed or metastatic disease
Symptomatic metastatic brain or meningeal tumors
No evidence of metastatic disease
Metastatic brain or meningeal tumors
Presence of >= 1 metastatic site (nodal, visceral) that is amenable to core biopsy
Evidence or suspicion of disease metastatic to sites remote from supratentorial brain
Patients with metastatic disease i.e. leptomeninges, multi-focal lesions in the CNS
Metastatic disease
CNS metastatic disease
Have extra-hepatic metastatic disease. Suspicious lesions should be rigorously evaluated with other imaging techniques and/or biopsy to exclude extra-hepatic metastatic disease prior to submitting for central radiology review.
Patient treated with more than one prior chemotherapy regimen for recurrent/metastatic disease
Patients with known metastatic disease are excluded
Pathologically (histologically or cytologically) confirmed metastatic disease with a new tumor involving or abutting bone that has the clinical and imaging features of metastatic disease\r\n* If the nature of the metastatic disease has been previously documented, index tumor to be treated does not require further documentation (i.e., biopsy)
Eligible subjects are required to have > or = to 1 line of multi-agent chemotherapy either neoadjuvantly or adjuvantly. Subjects may have had 0-2 lines of therapy for metastatic disease.
Histopathological documentation of MCC concurrent with the diagnosis of metastatic disease
Patients may not have received more than 2 prior systemic treatment regimens for distant metastatic disease. The following prior therapy is permitted in either the adjuvant or metastatic disease setting, provided treatment is discontinued at least 4 weeks prior to initiating study treatment:
Unresectable or metastatic disease
For non-urothelial cancer patients, no more than 1 prior line of combination systemic chemotherapy for metastatic disease is allowed
Metastatic cancer with evaluable disease
Patients in the phase I portion must have:\r\n* Histologically confirmed diagnosis of metastatic, genitourinary solid tumor\r\n* Metastatic disease defined as new or progressive lesions on cross-sectional imaging; patients must have at least:\r\n** One evaluable site of disease \r\n** Or, appearance of one new bone lesion
Subjects with negative metastatic involvement (M0).
Metastatic cervical or uterine cancer.
Metastatic or recurrent disease that is deemed partially resectable or unresectable based on preoperative imaging
Metastatic disease outside the confines of the abdomen and pelvis (such as lung, bone, brain)
Clinical or radiologic evidence of distant metastatic disease other than small volume (<1.5 cm) nodes, this should be tested within 12 months from enrollment;
Treatment with erlotinib prior to developing metastatic disease
Metastatic disease.
The diagnosis of metastatic disease will be fulfilled by one of two criteria: previous pathological diagnosis of cancer with suspicion of metastatic disease on imaging, and clinical diagnosis of metastatic disease; if there is not pathological diagnosis, a specimen will be sent to pathology at the time of the surgery to confirm malignancy
Documented presence of at least one metastatic lesion of the humerus.
Patients must have one focus of metastatic disease in the liver that is amenable to SBRT in the opinion of radiation oncology
Known N2 nodal disease or distant metastatic disease
Participants with evidence of non-hepatic metastatic disease
Failed treatment with one regimen containing at least a platinum/fluoropyrimidine doublet for unresectable or metastatic disease.Treatment failure is defined as progression of disease (clinical or radiologic) during first line treatment for unresectable or metastatic disease or ? 6 months after last dose of first line treatment.
No evidence of known metastatic disease (M0 or Mx allowed)
Patients must have unresectable or metastatic disease
Prior systemic therapy for metastatic disease.
Have histologically proven malignant adenocarcinoma of the pancreas; measurable disease is not required, mixed histology is not allowed; subjects must have metastatic disease
Pre-existing cancers and/or metastatic disease to the adrenal glands
Histologic diagnosis of unresectable or metastatic melanoma; for unknown primary disease, diagnosis of metastatic disease by cytology fine needle aspiration (FNA) is not acceptable
Documented evidence of distant metastasis or locoregional recurrence per required assessments within 28 days prior to starting study therapy. Note: Histologic confirmation of metastatic disease is not required.
Failed available therapy known to confer clinical benefit but no more than 4 prior lines of chemotherapy for metastatic disease.
Patients who have failed at least 1 systemic chemotherapy regimen for metastatic disease, but not more than 2 regimens
Patients must have demonstrated metastatic disease and not received > 2 lines of chemotherapy for metastatic disease (N/A for phase II)
For participants who present with de novo metastatic disease, no prior systemic chemotherapy is allowed
Symptomatic metastatic brain or meningeal tumors
progressive disease while receiving an AI for metastatic disease
May have received ?1 prior systemic chemotherapy regimen for metastatic disease.
Participants must have received prior systemic chemotherapy treatment for metastatic urothelial carcinoma. NOTE: Up to 2 prior systemic chemotherapeutic regimens given in the metastatic disease setting for urothelial carcinoma are allowed.
Subject must have unresectable or metastatic gastroesophageal adenocarcinoma.
Subject with previously untreated unresectable or metastatic gastroesophageal adenocarcinoma.
Adenocarcinoma of the stomach or gastroesophageal junction with inoperable, metastatic disease, not amenable to curative therapy
Presence of metastatic disease to the bone
Presence of distant metastatic disease; patients will undergo radiographic evaluation to exclude the possibility of distant metastatic disease; for patients who have undergone pre- or postoperative biopsies that definitively diagnose ICC, the diagnostic studies may be modified at the discretion of the MSKCC principal investigator; clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection
Patients with no prior therapy are eligible, provided they have metastatic disease that is not curable by surgery
Completely resected hepatic metastases without current evidence of other metastatic disease
Patients participating in the study must have metastatic (m)CRPC
Patients with one of the following diagnoses by histological diagnoses and by head and spine magnetic resonance imaging (MRI):\r\n* Classic histology metastatic medulloblastoma\r\n* Desmoplastic histology metastatic medulloblastoma\r\n* High-risk supratentorial, non-metastatic, PNET\r\n* Metastatic PNET
For participants in the second NSCLC cohort expansion, not more than two prior regimens in the metastatic setting
Surgically unresectable or metastatic disease.
More than 2 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease
Metastatic disease on baseline staging scans
The patient has another metastatic cancer disease.
Patients must have metastatic malignant melanoma or metastatic renal cell cancer (American Joint Committee on Cancer [AJCC] stage IV [M1] or equivalent disease); metastatic renal cell cancer patients must either have refused treatment with, have been unable to tolerate or have experienced progressive disease after treatment with sorafenib or sunitinib, and temsirolimus
No more than two prior chemotherapy regimens for metastatic disease
At least one line of endocrine therapy in the metastatic setting
Must have a biopsy in the metastatic setting with HER2 expression of 1+ or 2+ by IHC
If biopsy of metastatic lesion is performed prior to study entry, HER2 expression by IHC must be 1+ or 2+
HER2 0 or 3+ by IHC on pre-treatment biopsy of metastatic lesion (if performed)
Patients with known primary or metastatic CNS disease, are eligible for participation in cohort B, but not in cohort A
Patients with metastatic disease who are eligible for first line FOLFOX chemotherapy. Adjuvant or neoadjuvant given at least 12 months prior for non-metastatic disease is permitted.
Patients who had received Oxaliplatin within 12 months prior to diagnosis of metastatic disease.
Presence of metastatic disease in other locations in addition to the lung.
Metastatic disease outside of liver
Presence of a metastatic lesion greater than 1 cm in size that is amenable to radiation treatment
Has distant metastatic disease on imaging or staging laparoscopy at the time of study entry
Radiographic evidence measurable of residual or metastatic disease after surgery
Phase II: Patients with histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma that have not received systemic chemotherapy for advanced or metastatic disease; the definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by integrating the histopathological data within the context of the clinical and radiographic data
No prior chemotherapy for metastatic disease
No evidence of distant metastatic disease
Patients with evidence of distant metastatic disease
Evidence of metastatic disease on imaging studies
Evidence or suspected recurrent or metastatic disease; prior brain irradiation is not allowed
Definitive clinical or radiologic evidence of metastatic disease; if applicable
Metastatic cancer
Patients with metastatic disease
Patients with advanced prostate cancer suitable for systemic treatment defined as: having metastatic disease, a biochemical relapse after primary therapy, or patients in whom primary therapy is not appropriate or feasible; patients without metastatic disease will need evaluation for local therapy and deemed inappropriate or have refused this treatment option
Prior treatment with >1 chemotherapy regimen for metastatic disease
Have metastatic cancer
Patients with metastatic disease (BREAST ONLY)
Patients with metastatic disease
Presence of metastatic disease
Patients with widespread metastatic disease (> 3 distant metastases); patients with oligometastatic disease (=< 3 distant metastases) are allowed only if they are receiving definitive (curative) radiation therapy (RT) with or without chemotherapy
Diagnosis of pathologically confirmed metastatic pancreatic, hepatobiliary, esophageal, or lung cancer, either newly metastatic or metastatic at presentation (M1+) and enrollment within 6 weeks of diagnosis; measurable disease need not be present
Clinical evidence of metastatic disease
Free of macro-metastatic disease
Metastatic solid tumors
Survivors must not have evidence of recurrent or metastatic disease
Any spinal cord compromise or instrumentation due to metastatic disease; radiation therapy for metastatic disease is allowed
RENAL CANCER: Metastatic disease, in the opinion of the treating provider
RENAL CANCER: Starting any systemic therapy for metastatic disease
Systemic disease burden with metastatic tumor to the brain
Presence of metastatic disease
Presence of metastatic disease
Patients seen in the SCC with a diagnosis of cancer with or without evidence of metastatic disease
Have no evidence of recurrence or metastatic disease
Symptomatic metastatic brain or meningeal tumors
Patients with evidence of muscle-invasion or metastatic disease will be excluded
Patients who have known metastatic disease or other bulk disease in the thoracic or cervical regions
Patients with evidence of distant metastatic PDAC
Metastatic disease of any kind
Histologically or cytologically confirmed locally mEC or metastatic adenocarcinoma of the GEJ Siewert Classification Type I in participants who have not received prior systemic therapy for primary and metastatic disease or chemoradiation therapy for primary disease
Subject with metastatic disease
Participants with known metastatic disease should be excluded from this clinical trial
Distant metastatic disease at the time of enrollment
Known metastatic disease
Evidence of or treatment for metastatic disease
Informed of metastatic disease within the previous 8 weeks
No prior therapy for metastatic disease
Presence of metastatic disease
Metastatic bone disease with metastatic disease previously confirmed by prior biopsy; or Metastatic bone disease previously confirmed on imaging [e.g. computed tomography (CT) or magnetic resonance imaging (MRI)] with known (biopsied) primary disease (primary bone cancer is excluded)
Pain must be from one or two painful metastatic sites in the bone that is amenable to cryoablation with CT or MRI (additional less painful metastatic sites may be present)
Gross nodal or metastatic disease at presentation (>= N1, M1)
All patients with metastatic pancreas cancer will be eligible
There is no limit to the amount of prior therapy for metastatic disease
Patients who have tumors other than metastatic pancreas cancer
Patients with metastatic disease
Metastatic disease
Known distant metastatic disease
Participants with biopsy proven metastatic disease (M1)
Clinical or radiographic evidence of metastatic disease
Absence of metastatic disease as documented by radiographic scans
Clinical evidence of metastatic (T4b, any N; any T, N2-3; M1) disease
Clinical or radiological evidence of metastatic disease
Prior treatment with a taxane in the metastatic setting
Patients with metastatic disease
Patient must NOT have human epidermal growth factor-2 positive (HER2+) metastatic disease
Patient must NOT have received prior endocrine therapy for metastatic disease (i.e., must be first-line endocrine therapy for metastatic disease)
Initiation of new therapy for recurrent and/or progressive metastatic disease since radiographic documentation of recurrence/progression.
Metastatic disease
Metastatic disease outside of pelvis on any imaging or biopsy
Histologically confirmed diagnosis of malignant primary brain tumor or known metastatic cancer with brain lesion presumed to be metastatic
More than one metastatic cancer active in the last 5 years
Patients have no clinical evidence of distant metastatic disease
Scheduled to undergo radioimmunotherapy (RIT) for metastatic disease
Unresectable or metastatic SCCHN.
Plan to start a new systemic therapy for metastatic disease
Multifocal metastatic disease in either castrate sensitive or castrate resistant patients
Have regional or distant metastatic disease
For patients with metastatic renal tumors to be enrolled, a histologic diagnosis of renal cell carcinoma must exist and any burden of disease >= 1 cm by CT or MRI is acceptable; the metastatic sites may be kidney, intra-abdominal (such as liver), brain, bone, or lymph nodes; lung lesions are NOT eligible because of the motion artifact caused by respiration
Clinically distant metastatic disease, either M1a/M1b/M1c
Metastatic spinal lesions 1 cm or greater in diameter
Known metastatic thyroid cancer
Patient can remain on androgen deprivation therapy if on the same regimen prior to documentation of progressive metastatic disease
Initiation of new therapy for progressive metastatic disease since radiographic documentation of progression
Patients with known metastatic disease
Patients with nodal disease or distant metastatic disease
Patients with any metastatic disease
Participants with known clinical or radiographic evidence of metastatic CNS disease
Patients with known metastatic disease
Patient may have distant metastatic disease provided the estimated survival is at least 1 year
Participants must be women who have histological confirmation of metastatic invasive breast cancer that has metastasized outside the region of the primary tumor and axilla; biopsy must be obtained prior to initiation of chemotherapy; it should be performed within 28 days prior to enrollment (patients with a biopsy of recurrent disease that is HER2-positive and have not received HER2-directed therapy since the biopsy can exceed the 28-day window up to 6 months); patients must have metastatic disease in lung, liver, soft-tissue or bone to qualify for the study (more than one site is permissible)
No metastatic sites >= 20 mm
Zero or one prior chemotherapy regimens for metastatic disease
Patients must already be known to have metastatic, incurable cancer
Radiographic evidence of metastatic disease
Patients with metastatic disease
Patients with a history of CRC without clear evidence of metastatic disease who have completed their acute cancer-specific treatment
Patients with distant metastatic disease will be eligible if they satisfy all other conditions
For salvage setting patients: Metastatic Disease at PSA rise
The patient has known distant metastatic disease
Is unresectable or metastatic
Have confirmed metastatic disease
History cancer with no limitation on prior lines of therapy in the metastatic setting
Patient: Does not have metastatic disease
Does not have metastatic disease
Exclude any patient who has a history of metastatic cancer
No evidence of metastatic disease
Diagnosis of unresectable or metastatic melanoma
Phase 3: Previous treatment with 3 or more systemic regimens given for recurrent and/or metastatic disease
Patients must have currently progressive metastatic disease according to RECIST v1.1\n             criteria, AND
They have progressed on at least one previous line of endocrine therapy (ET) for\n                  their metastatic disease (but are not currently progressing on fulvestrant), OR;
Patient is about to start a new line of ET for their metastatic disease
Patients have either metastatic or non-metastatic lung cancer as defined in history and physical
One, 2, or 3 prior lines of chemotherapy for metastatic disease and with progression of disease on last treatment regimen.
Part A: must be chemotherapy naïve for metastatic NSCLC
Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive by an FDA-approved assay performed centrally. Patients must be ALK positive by local test prior to submitting tissue to the central lab. Randomization will occur after ALK positive confirmation is received from the central lab. Patients may have received up to 1 prior chemotherapy regimen for metastatic disease, which may also include maintenance therapy. Note that patients that have received adjuvant or neoadjuvant chemotherapy and developed metastatic disease within 6 months from the end of that therapy would be considered to have received 1 prior regimen for metastatic disease.
Patients with distant metastatic disease (cM1) or a life expectancy of less than 5 years