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

Sponsor

Hospital de Cancer de Barretos - Fundacao Pio XII (Other)

Overall Status

Unknown status

CT.gov ID

NCT01859728

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate safety and efficacy of the combination cisplatin plus irinotecan in the treatment of biliary tract cancer.

Condition or Disease	Intervention/Treatment	Phase
Biliary Cancer	Drug: Irinotecan Drug: Cisplatin Drug: Cisplatin Drug: Gemcitabine	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 2013

Anticipated Primary Completion Date :

Dec 1, 2018

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: IP (irinotecan and cisplatin)

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

Irinotecan 65mg/m² D1 and D8 q21 days, until disease progression or unacceptable toxicity. Given in association with standard hydration and anti-emetics.

Other Names:

CPT-11

Drug: Cisplatin

Cisplatin 60mg/m² D1 q 21 days, until disease progression or unacceptable toxicity. Given in association with standard hydration and anti-emetics.

Other Names:

CDDP

Active Comparator: GC (gemcitabine and cisplatin)

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

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.

Other Names:

CDDP

Drug: Gemcitabine

Gemcitabine 1000mg/m² D1 and D8 every 21 days, until disease progression or unacceptable toxicity. Given in association with standard hydration and anti-emetics.

Outcome Measures

Primary Outcome Measures

Overall Response Rate [Up to 24 weeks from randomization]
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.

Secondary Outcome Measures

Progression-Free Survival (PFS) [6mo after the last enrolled patient]
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.
Overall Survival (OS) [6mo after the last enrolled patient]
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.
Disease Control Rate [Up to 6 weeks from randomization]
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.
Safety [6 mo after the last enrolled patients]
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.

Other Outcome Measures

Biomarker evaluation [Baseline]
The following biomarkers will be tested by immunohistochemistry: human equilibrative nucleoside transporter (hENT), X-ray repair cross-complementing protein 1 (XRCC1), Excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) e mLH1. Then we will correlate them with efficacy end-points using non-parametric test.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;