GAMBIT Trial: Cisplatin Plus Irinotecan in the Treatment of Gallbladder or Biliary Tract Cancer

Study Overview
=================
Brief Summary
-----------------
To evaluate safety and efficacy of the combination cisplatin plus irinotecan in the treatment of biliary tract cancer.

Official Title
-----------------
GAMBIT Trial: A Randomized,Non-comparative, Open-label Clinical Trial Evaluating Cisplatin Plus Irinotecan in the Treatment of Gallbladder or Biliary Tract Cancer

Conditions
-----------------
Biliary Cancer

Intervention / Treatment
-----------------
* Drug: Irinotecan
* Drug: Cisplatin
* Drug: Cisplatin
* Drug: Gemcitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: biopsy-proven gallbladder or biliary tract cancer; Recurrent, metastatic or unresectable disease; Chemo-naïve. Not candidates to curative-intent treatment, such as surgery or radiation-therapy; Measurable disease according to RECIST 1.1; ECOG 0-2; Adequate hematologic and biochemistry tests; Creatinine clearance >= 60ml/min. Exclusion Criteria: Known hypersensibility or previous therapy with cisplatin, gemcitabine or irinotecan; Chronic immunosuppressive therapy; Known CNS metastasis; Previous diagnosis of other cancer; Chronic or acute active infection, except asymptomatic HIV infection; Active bleeding; Any severe medical condition; Pregnant or lactating women, or with childbearing potential;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IP (irinotecan and cisplatin)<br>Irinotecan 65mg/m² D1 and D8 q21 days plus Cisplatin 60mg/m² D1 q 21 days, until disease progression or unacceptable toxicity, with standard hydration and antiemetics. | Drug: Irinotecan<br>* Irinotecan 65mg/m² D1 and D8 q21 days, until disease progression or unacceptable toxicity. Given in association with standard hydration and anti-emetics.<br>* Other names: CPT-11;Drug: Cisplatin<br>* Cisplatin 60mg/m² D1 q 21 days, until disease progression or unacceptable toxicity. Given in association with standard hydration and anti-emetics.<br>* Other names: CDDP;|
| Active Comparator: GC (gemcitabine and cisplatin)<br>Gemcitabine 1000mg/m² D1 and D8 every 21 days plus cisplatin 25mg/m² D1 and D8 every 21 days, until disease progression or unacceptable toxicity, with standard hydration and antiemetics. | Drug: Cisplatin<br>* Cisplatin 25mg/m² D1 and D8 every 21 days, until disease progression or unacceptable toxicity. , with standard hydration and antiemetics. Given in association with standard hydration and anti-emetics.<br>* Other names: CDDP;Drug: Gemcitabine<br>* Gemcitabine 1000mg/m² D1 and D8 every 21 days, until disease progression or unacceptable toxicity. Given in association with standard hydration and anti-emetics.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | The overall response rate will measure the number of subjects with complete or partial response as best response during the entire treatment, over the total number of subjects, for each arm. The response will be evaluated according to RECIST 1.1. | Up to 24 weeks from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | We will measure the number of subjects without progressive disease (complete response, partial response or stable disease) or any-cause death, whichever came first. For each patient, PFS will be calculated from randomization until progressive disease. Disease progression means radiologic progression per RECIST 1.1 or any-cause death. PFS will also be analysed with log-rank test, and reported as HR with respective 95% CI and p value, and median PFS will be estimated with kaplan-meyer method. All calculations will be performed 6 months after the last patient recruited. Also, the PFS rate at one and two years will be calculated. | 6mo after the last enrolled patient | 
| Overall Survival (OS) | We will measure the number of subjects without any-cause death. For each patient, OS will be calculated from randomization until death. OS will also be analysed with log-rank test, and reported as HR with respective 95% CI and p value, and median OS will be estimated with kaplan-meyer method. All calculations will be performed 6 months after the last patient recruited. Also, the survival rate at one and two years will be calculated. | 6mo after the last enrolled patient | 
| Disease Control Rate | The disease control rate will measure the number of subjects with complete or partial response, or disease stabilization as best response during the entire treatment, over the total number of subjects, for each arm. The response will be evaluated according to RECIST 1.1. | Up to 6 weeks from randomization | 
| Safety | Safety and tolerability will be assessed using NCI CTCAE v3. The number of patients in each arm experiencing any grade Adverse Events (for each AE) and Serious AE (SAE) over the total number of subjects will be measured, and the proportion of patients experiencing AE in each arm will be compared using uncorrected chi-sq test. AE will be recorded in baseline and in each visit, and the worst grade AE will be considered. Each AE will be classified in grades 1-2, 3-4 and SAE. | 6 mo after the last enrolled patients | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
biliary cancer, irinotecan, cisplatin, gemcitabine