Safety of Combining Irinotecan With 5-FU, Leucovorin/Folinic Acid, Oxaliplatin, and Docetaxel Chemotherapies
- Conditions
- Pancreatic AdenocarcinomaGastroesophageal Junction AdenocarcinomaAdenocarcinoma
- Interventions
- Registration Number
- NCT04361708
- Lead Sponsor
- University of Chicago
- Brief Summary
The purpose of the proposed study is to establish the safety of combining irinotecan chemotherapy with 5-FU, leucovorin/folinic acid, oxaliplatin, and docetaxel (abbreviated as the I-FLOAT study of gFOLFOXIRITAX) chemotherapies (leucovorin/folinic acid is a vitamin to make 5-FU work well).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 54
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Histologically or cytologically confirmed locally advanced or metastatic pancreatic adenocarcinoma, gastroesophageal adenocarcinoma, cholangiocarcinoma, gallbladder adenocarcinoma, ampullary carcinoma, adenocarcinoma of unclear primary (with upper GI primary suspected), or other primary GI malignancy for which the treating physician feels that I-FLOAT is a reasonable therapeutic option.
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Patients with a history of obstructive jaundice due to the primary tumor must have resolved to <1.5 X upper limit of normal and a metal biliary stent in place
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Age greater than or equal to 18 years.
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Eastern Cooperative Oncology Group (ECOG) performance status =1
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Life expectancy > 3 months
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Adequate organ function, as defined by each of the following:
Absolute neutrophil count (ANC) = 1500/uL Hemoglobin > 9g/dL (transfusion permitted with stability for > 1 week) Platelets > 100,000/uL Total bilirubin = 1.5 mg/dL AST and ALT = 2.5 X upper limit of normal; alkaline phosphatase = 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis.
AST and ALT = 5 X upper limit of normal if hepatic metastases are present. Creatinine = 1.5 mg/dL
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Measurable or non-measurable disease will be allowed.
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Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment.
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Negative serum or urine B-hCG pregnancy test at screening for patients of childbearing potential
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Patients taking substrates, inhibitors, or inducers of CYP3A4 should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with irinotecan.
- Prior radiation therapy for any cancer.
- Prior chemotherapy for metastatic disease Recurrence of disease within 6 months of perioperative chemotherapy are eligible if other eligibility criteria are met
- Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Diarrhea, grade 1 or greater by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, v. 4.0*). Pancreatic cancer patients with clinical evidence of pancreatic insufficiency must be taking pancreatic enzyme replacement.
- Neuropathy, grade 2 or greater by NCI-CTCAE, v. 4.0.
- Documented brain metastases
- Serious underlying medical or psychiatric illnesses that would, in the opinion of the treating physician, substantially increase the risk for complications related to treatment.
- Active uncontrolled bleeding.
- Pregnancy or breastfeeding.
- Major surgery within 4 weeks.
- Previous or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer for which the patient has been previously treated and the lifetime recurrence risk is less than 30%, and meets all other eligibility criteria.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description High Risk UGT1A1 genotype Oxaliplatin - High Risk UGT1A1 genotype Leucovorin - High Risk UGT1A1 genotype Docetaxel - High Risk UGT1A1 genotype Irinotecan - High Risk UGT1A1 genotype 5-Fluorouracil - Intermediate Risk UGT1A1 genotype Oxaliplatin - Intermediate Risk UGT1A1 genotype Docetaxel - Intermediate Risk UGT1A1 genotype Leucovorin - Intermediate Risk UGT1A1 genotype Irinotecan - Intermediate Risk UGT1A1 genotype 5-Fluorouracil - Low Risk UGT1A1 genotype Oxaliplatin - Low Risk UGT1A1 genotype Docetaxel - Low Risk UGT1A1 genotype Leucovorin - Low Risk UGT1A1 genotype Irinotecan - Low Risk UGT1A1 genotype 5-Fluorouracil -
- Primary Outcome Measures
Name Time Method The maximum dose tolerated 1 month To determine the maximum tolerated dose in the first month of therapy in each of the three main genotype groups (low, intermediate, and high risk) using genotype-guided dosing of irinotecan as part of the I-FLOAT regimen
- Secondary Outcome Measures
Name Time Method Cumulative dose of each chemotherapy drug 4 months To determine the cumulative dose of each chemotherapy drug (irinotecan, 5-FU, oxaliplatin, docetaxel) administered in each genotype group over a period of 4 months (8 doses).
Total duration of therapy 18 months To determine the total duration of therapy, which would be administered perioperatively in future studies for the curative-intent setting.
Overall survival rate 5 years To determine early efficacy (overall responsive rate, progression free survival, and overall survival) in all patients enrolled and treated in the study.
Overall Response Rate 5 years To determine early efficacy (overall responsive rate, progression free survival, and overall survival) in all patients enrolled and treated in the study.
Progression free survival rate 5 years To determine early efficacy (overall responsive rate, progression free survival, and overall survival) in all patients enrolled and treated in the study.
Trial Locations
- Locations (1)
The University of Chicago
🇺🇸Chicago, Illinois, United States