Phase II Study of FOLFOXIRI in Patients With Locally Advanced or Metastatic Biliary Tract Cancer

Study Overview
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Brief Summary
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Goals The primary goal of this phase II trial is to: evaluate the response rate of combination chemotherapy with Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan in patients with locally advanced or metastatic Biliary tract cancer as first-line chemotherapy Secondary goals are to: evaluate the treatment-related toxicities of this combination, investigate progression-free survival(PFS) and overall survival(OS) in this population Design The proposed clinical trial is an open label, non-comparative, multicenter phase II trial according to the two stage testing design by Simon two-stage testing procedure

Official Title
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Multicenter Phase II Study of Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) in Patients With Locally Advanced or Metastatic Biliary Tract Cancer

Conditions
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Biliary Tract Cancer

Intervention / Treatment
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* Drug: Fluorouracil
* Drug: Leucovorin
* Drug: Oxaliplatin
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who were diagnosed as adenocarcinoma of gallbladder or biliary tract histologically or cytologically Unresectable locally advanced, metastatic, or recurrent biliary tract cancer Patients must be ≥ 18 , ≤ 75 years old of age ECOG performance status ≤ 2 At least one lesion that can be measured by imaging (CT/MRI) according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) Estimated life expectancy of more than 3 months Adequate bone marrow function (absolute neutrophil count [ANC] ≥ 1,500/µL, hemoglobin ≥ 9.0 g/dL [correction by transfusion is acceptable], and platelets ≥ 100,000/µL) Adequate kidney function (serum creatinine < 1.5 x upper limit of normal [ULN]) Adequate liver function (serum total bilirubin < 3.0xULN; serum transaminases levels < 5.0xUNL) Provision of fully informed consent prior to any study specific procedures Exclusion Criteria: Other tumor type than adenocarcinoma Any previous history of chemotherapy for biliary tract cancer (prior neoadjuvant/adjuvant chemotherapy is allowed, if recurrence occurred more than 6 months after completion of previous chemotherapy) Patients with second primary cancer (except, adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥5 years) Patients who received radiotherapy on target lesion within 6 months prior to study treatment Patients with defect of central nervous system (CNS) or any psychiatric disorders and CNS metastases Patients who received major surgery within 4 weeks of starting study treatment or was not recovered from any effects of major surgery Pregnant or breastfeeding women and women of childbearing potential not employing adequate contraception Other serious illness or medical conditions A. Clinically significant cardiac disease (uncontrolled congestive heart disease despite treatment [NYHA class III or IV], symptomatic coronary artery disease, unstable angina or myocardial infarction, conduction abnormality like grade 2 AV block, serious arrhythmia needed for medication, uncontrolled hypertension) within 6 months prior to study entry B. Liver cirrhosis (≥ Child-Pugh class B) C. History of significant neurologic or psychiatric disorders including dementia or seizures D. Active uncontrolled infection E. Other serious underlying medical conditions which could impair the ability of the patient to participate in the study Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Fluorouracil|5-fluorouracil 2400 mg/m2 (diluted in 1000 ml of 5% dextrose solution) administered as a continuous intravenous infusion over 48 hours every 2 weeks|
|Drug: Leucovorin|Leucovorin 400 mg/m2 (diluted in 250 ml of 5% dextrose solution) as a 2-hour intravenous infusion every 2 weeks|
|Drug: Oxaliplatin|Oxaliplatin 85 mg/m2 (diluted in 250 ml of 5% dextrose solution) given as a 2-hour intravenous infusion every 2 weeks|
|Drug: Irinotecan|Irinotecan 150 mg/m2 (diluted in 250 ml of 0.9% normal saline solution) given as a 90-minute intravenous infusion every 2 weeks|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Assessment of response will be assessed according to RECIST v1.1 criteria after completion of every two cycles. Evaluation will be conducted by physical examination, X-ray, or CT scan | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related toxicities | Assessment of toxicity will be assessed according to NCI CTCAE version 4.0. | 2 years | 
| Progression free survival |  | 2 years | 
| Overall survival |  | 2 years |