{
"info": {
"nct_id": "NCT03536182",
"official_title": "CIPHER: A Prospective, Multi-Center Randomized Phase 3 Trial of Carbon Ion Versus Conventional Radiation Therapy for Locally Advanced, Unresectable Pancreatic Cancer",
"inclusion_criteria": "1. All patients must be willing and capable to provide informed consent within the 30 days prior to registration to participate in the protocol.\n2. Histological and/or cytological diagnosis of pancreas adenocarcinoma must be done at any point prior to registration\n3. Unresectable by radiographic or exploration within 30 days of registration\n4. Age ≥ 18 years.\n5. Distance from the pancreas tumor edge to the bowel and stomach > 3 mm (in both the prone and supine positions)\n6. Tumor does not exceed 15 cm in greatest dimension\n7. No evidence for metastatic disease as assessed by CT imaging of the chest, abdomen and pelvis OR by PET-CT within the 30 days prior to registration. Pancreas-protocol CT or magnetic resonance imaging (MRI) with gadolinium (for patients who cannot receive CT contrast) is required as part of this evaluation.\n8. Zubrod performance status of 0-1, within 30 days prior to registration.\n9. Adequate hematologic, renal, and liver function as defined by:Adequate hematologic, renal, and liver function as defined by:\n\n Absolute neutrophil count > 1500 cells/mm3 Creatinine <1.5 mg/dL Hemoglobin ≥ 8.0 g/dL AST and ALT < 2.5 X ULN Bilirubin ≤ 1.5 times the ULN (after stent placement, if necessary)\n10. Patients must complete all required pretreatment evaluations\n11. Able to travel to a foreign country within approximately 4 weeks of randomization (for patients enrolled outside of Japan and Italy)\n12. If a patient receives 1 or 2 cycles of chemotherapy at an outside facility, pre-treatment laboratory values must meet the above criteria. If the protocol-compliant imaging had not been obtained prior to chemotherapy, they may be performed prior to registration and any additional chemotherapy being infused.\n13. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.\n\nA female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:\n\n* Has not undergone a hysterectomy or bilateral oophorectomy; or\n* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).\nHealthy volunteers allowed\nMust have minimum age of 18 Years\nMust have maximum age of 120 Years",
"exclusion_criteria": "1. Subjects receiving other investigational agents.\n2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or nab-paclitaxel or other agents used in study.\n3. Subjects who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.\n4. Prior radiation to the upper abdomen\n5. Placement of a metal stent for relief of biliary obstruction (metal stents may be placed following completion of radiation therapy).\n6. Body weight >100 kg\n7. Active inflammatory bowel disease or active gastric/duodenal ulcer\n8. Metal implants in the upper abdomen\n9. Expected medical intolerance of radiotherapy, concurrent chemotherapy, and/or adjuvant chemotherapy.\n10. History of HIV or hepatitis B or C",
"miscellaneous_criteria": ""
},
"inclusion_lines": [
{
"identified_line": {
"line": "1. All patients must be willing and capable to provide informed consent within the 30 days prior to registration to participate in the protocol.",
"criterions": [
{
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"expected_value": true
}
},
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}
},
{
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"requirement_type": "timing",
"expected_value": {
"operator": "<=",
"value": 30,
"unit": "days"
}
}
}
]
},
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"and_criteria": [
{
"and_criteria": [
{
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"unit": "days"
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}
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}
},
{
"identified_line": {
"line": "3. Unresectable by radiographic or exploration within 30 days of registration",
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{
"exact_snippets": "Unresectable by radiographic or exploration",
"criterion": "tumor resectability",
"requirement": {
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"expected_value": [
"radiographic",
"exploration"
]
}
},
{
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}
}
]
},
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{
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}
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}
}
]
}
},
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"identified_line": {
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{
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"operator": ">=",
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"unit": "years"
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}
}
]
},
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{
"exact_snippets": "Age ≥ 18 years.",
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"line": "6. Tumor does not exceed 15 cm in greatest dimension",
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{
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"unit": "cm"
}
}
}
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],
"exclusion_lines": [],
"miscellaneous_lines": [],
"failed_inclusion": [
{
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{
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]
}
},
{
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"criterion": "pancreas adenocarcinoma diagnosis",
"requirement": {
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}
}
]
},
"logical_structure": {
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"or_criteria": [
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}
},
{
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}
}
]
},
{
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}
}
]
}
},
{
"identified_line": {
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{
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"unit": "mm"
}
}
},
{
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]
}
}
]
},
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{
"and_criteria": [
{
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}
},
{
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"criterions": [
{
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"criterion": "metastatic disease",
"requirement": {
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"expected_value": false
}
},
{
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"requirement_type": "body parts",
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"abdomen",
"pelvis"
]
}
},
{
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"criterion": "PET-CT",
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}
},
{
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"requirement": {
"requirement_type": "type",
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"MRI with gadolinium"
]
}
}
]
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{
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"requirement": {
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{
"operator": ">=",
"value": 0,
"unit": "N/A"
},
{
"operator": "<=",
"value": 1,
"unit": "N/A"
}
]
}
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}
}
]
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},
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"criterions": [
{
"exact_snippets": "Adequate hematologic ... function",
"criterion": "hematologic function",
"requirement": {
"requirement_type": "adequacy",
"expected_value": true
}
},
{
"exact_snippets": "Adequate ... renal ... function",
"criterion": "renal function",
"requirement": {
"requirement_type": "adequacy",
"expected_value": true
}
},
{
"exact_snippets": "Adequate ... liver function",
"criterion": "liver function",
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}
}
]
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},
{
"identified_line": {
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"criterions": [
{
"exact_snippets": "Absolute neutrophil count > 1500 cells/mm3",
"criterion": "absolute neutrophil count",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">",
"value": 1500,
"unit": "cells/mm3"
}
}
},
{
"exact_snippets": "Creatinine <1.5 mg/dL",
"criterion": "creatinine",
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"operator": "<",
"value": 1.5,
"unit": "mg/dL"
}
}
},
{
"exact_snippets": "Hemoglobin ≥ 8.0 g/dL",
"criterion": "hemoglobin",
"requirement": {
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 8.0,
"unit": "g/dL"
}
}
},
{
"exact_snippets": "AST and ALT < 2.5 X ULN",
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"operator": "<",
"value": 2.5,
"unit": "X ULN"
}
}
},
{
"exact_snippets": "Bilirubin ≤ 1.5 times the ULN (after stent placement, if necessary)",
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"requirement": {
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"expected_value": {
"operator": "<=",
"value": 1.5,
"unit": "times the ULN"
}
}
}
]
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{
"exact_snippets": "complete all required pretreatment evaluations",
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"expected_value": true
}
}
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},
{
"identified_line": {
"line": "11. Able to travel to a foreign country within approximately 4 weeks of randomization (for patients enrolled outside of Japan and Italy)",
"criterions": [
{
"exact_snippets": "Able to travel to a foreign country",
"criterion": "ability to travel",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "within approximately 4 weeks of randomization",
"criterion": "timeframe for travel",
"requirement": {
"requirement_type": "timeframe",
"expected_value": {
"operator": "<=",
"value": 4,
"unit": "weeks"
}
}
},
{
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"criterion": "enrollment location",
"requirement": {
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]
}
}
]
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},
{
"identified_line": {
"line": "12. If a patient receives 1 or 2 cycles of chemotherapy at an outside facility, pre-treatment laboratory values must meet the above criteria. If the protocol-compliant imaging had not been obtained prior to chemotherapy, they may be performed prior to registration and any additional chemotherapy being infused.",
"criterions": [
{
"exact_snippets": "1 or 2 cycles of chemotherapy at an outside facility",
"criterion": "cycles of chemotherapy",
"requirement": {
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"expected_value": {
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{
"operator": "=",
"value": 1,
"unit": "cycles"
},
{
"operator": "=",
"value": 2,
"unit": "cycles"
}
]
}
}
},
{
"exact_snippets": "pre-treatment laboratory values must meet the above criteria",
"criterion": "pre-treatment laboratory values",
"requirement": {
"requirement_type": "compliance",
"expected_value": "must meet the above criteria"
}
},
{
"exact_snippets": "protocol-compliant imaging had not been obtained prior to chemotherapy",
"criterion": "protocol-compliant imaging",
"requirement": {
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"expected_value": "had not been obtained prior to chemotherapy"
}
}
]
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},
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"identified_line": {
"line": "13. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.",
"criterions": [
{
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"criterion": "women of childbearing potential",
"requirement": {
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"expected_value": true
}
},
{
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"criterion": "men contraception agreement",
"requirement": {
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"expected_value": true
}
},
{
"exact_snippets": "Women of childbearing potential ... must agree to use adequate contraception",
"criterion": "women contraception agreement",
"requirement": {
"requirement_type": "agreement",
"expected_value": true
}
}
]
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"identified_line": {
"line": "A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:",
"criterions": [
{
"exact_snippets": "female",
"criterion": "gender",
"requirement": {
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"expected_value": "female"
}
},
{
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"requirement": {
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"expected_value": "child-bearing potential"
}
}
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"criterion": "hysterectomy",
"requirement": {
"requirement_type": "underwent",
"expected_value": false
}
},
{
"exact_snippets": "bilateral oophorectomy",
"criterion": "bilateral oophorectomy",
"requirement": {
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"expected_value": false
}
}
]
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"criterions": [
{
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"expected_value": {
"operator": "<",
"value": 12,
"unit": "months"
}
}
},
{
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"criterion": "menstrual cycle",
"requirement": {
"requirement_type": "occurrence",
"expected_value": true
}
}
]
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}
}
]
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},
{
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"criterions": [
{
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"expected_value": {
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"value": 18,
"unit": "Years"
}
}
}
]
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}
}
},
{
"identified_line": {
"line": "Must have maximum age of 120 Years",
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{
"exact_snippets": "maximum age of 120 Years",
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"requirement_type": "maximum",
"expected_value": {
"operator": "<=",
"value": 120,
"unit": "Years"
}
}
}
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],
"failed_exclusion": [
{
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{
"exact_snippets": "Subjects receiving other investigational agents",
"criterion": "receiving investigational agents",
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"expected_value": true
}
}
]
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}
}
},
{
"identified_line": {
"line": "2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or nab-paclitaxel or other agents used in study.",
"criterions": [
{
"exact_snippets": "History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine",
"criterion": "allergic reactions to gemcitabine-like compounds",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "History of allergic reactions attributed to compounds of similar chemical or biologic composition to ... nab-paclitaxel",
"criterion": "allergic reactions to nab-paclitaxel-like compounds",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "History of allergic reactions attributed to compounds of similar chemical or biologic composition to ... other agents used in study",
"criterion": "allergic reactions to other study agents",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
}
]
},
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}
}
},
{
"identified_line": {
"line": "3. Subjects who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.",
"criterions": [
{
"exact_snippets": "Subjects who are pregnant",
"criterion": "pregnancy",
"requirement": {
"requirement_type": "presence",
"expected_value": false
}
},
{
"exact_snippets": "nursing",
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"requirement_type": "presence",
"expected_value": false
}
}
]
},
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},
{
"identified_line": {
"line": "4. Prior radiation to the upper abdomen",
"criterions": [
{
"exact_snippets": "Prior radiation to the upper abdomen",
"criterion": "radiation to the upper abdomen",
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"requirement_type": "prior treatment",
"expected_value": true
}
}
]
},
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}
}
},
{
"identified_line": {
"line": "5. Placement of a metal stent for relief of biliary obstruction (metal stents may be placed following completion of radiation therapy).",
"criterions": [
{
"exact_snippets": "Placement of a metal stent for relief of biliary obstruction",
"criterion": "metal stent placement",
"requirement": {
"requirement_type": "purpose",
"expected_value": "relief of biliary obstruction"
}
},
{
"exact_snippets": "metal stents may be placed following completion of radiation therapy",
"criterion": "metal stent placement",
"requirement": {
"requirement_type": "timing",
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}
}
]
},
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}
},
{
"identified_line": {
"line": "6. Body weight >100 kg",
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{
"exact_snippets": "Body weight >100 kg",
"criterion": "body weight",
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"requirement_type": "value",
"expected_value": {
"operator": ">",
"value": 100,
"unit": "kg"
}
}
}
]
},
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}
},
{
"identified_line": {
"line": "7. Active inflammatory bowel disease or active gastric/duodenal ulcer",
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{
"exact_snippets": "Active inflammatory bowel disease",
"criterion": "inflammatory bowel disease",
"requirement": {
"requirement_type": "activity",
"expected_value": "active"
}
},
{
"exact_snippets": "active gastric/duodenal ulcer",
"criterion": "gastric/duodenal ulcer",
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"requirement_type": "activity",
"expected_value": "active"
}
}
]
},
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}
},
{
"identified_line": {
"line": "8. Metal implants in the upper abdomen",
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{
"exact_snippets": "Metal implants in the upper abdomen",
"criterion": "metal implants",
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"requirement_type": "location",
"expected_value": "upper abdomen"
}
}
]
},
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}
}
},
{
"identified_line": {
"line": "9. Expected medical intolerance of radiotherapy, concurrent chemotherapy, and/or adjuvant chemotherapy.",
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{
"exact_snippets": "Expected medical intolerance of radiotherapy",
"criterion": "medical intolerance to radiotherapy",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "Expected medical intolerance of ... concurrent chemotherapy",
"criterion": "medical intolerance to concurrent chemotherapy",
"requirement": {
"requirement_type": "presence",
"expected_value": true
}
},
{
"exact_snippets": "Expected medical intolerance of ... adjuvant chemotherapy",
"criterion": "medical intolerance to adjuvant chemotherapy",
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"requirement_type": "presence",
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}
}
]
},
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}
},
{
"identified_line": {
"line": "10. History of HIV or hepatitis B or C",
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{
"exact_snippets": "History of HIV",
"criterion": "HIV",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "hepatitis B",
"criterion": "hepatitis B",
"requirement": {
"requirement_type": "history",
"expected_value": true
}
},
{
"exact_snippets": "hepatitis C",
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"requirement_type": "history",
"expected_value": true
}
}
]
},
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}
],
"failed_miscellaneous": []
}