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

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

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

Study Overview

• Status: Unknown
• Conditions: Biliary Cancer
• Intervention / Treatment: Drug: Irinotecan; Drug: Cisplatin; Drug: Cisplatin; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lucas V dos Santos, MD; Phone Number: +5517-81544670; Email: lucasvsantos@yahoo.com
• Study Contact Backup: Name: Kathia C Abdalla, MD; Phone Number: 6829 +551733216600; Email: kathia.abdalla@hcancerbarretos.com.br

Study Locations

• Brazil
  • SP
    • Barretos, SP, Brazil, 14784400
      • Recruiting
      • Barretos Cancer Hospital
      • Contact: Kathia C Abdalla, MD; Phone Number: 6829 +551733216600; Email: kathia.abdalla@hcancerbarretos.com.br
      • Contact: Lucas V. dos Santos, M.D.; Phone Number: +551781544670; Email: lucasvsantos@yahoo.com
      • Principal Investigator: Kathia C Abdalla, MD
      • Sub-Investigator: Arinilda C Bragagnoli, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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; 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
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 60mg/m² D1 q 21 days, until disease progression or unacceptable toxicity. Given in association with standard hydration and anti-emetics.; Other Names: CDDP; 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.

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker evaluation	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.	Baseline

Collaborators and Investigators

• Sponsor: Hospital de Cancer de Barretos - Fundacao Pio XII
• Investigators: Study Chair: Lucas V dos Santos, MD, Barretos Cancer Hospital; Principal Investigator: Kathia C Abdalla, MD, Barretos Cancer Hospital; Study Director: Joao Paulo S N Lima, MD, PhD, Barretos Cancer Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: May 14, 2013
• First Submitted That Met QC Criteria: May 21, 2013
• First Posted (Estimate): May 22, 2013

Study Record Updates

• Last Update Posted (Actual): January 18, 2018
• Last Update Submitted That Met QC Criteria: January 17, 2018
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: cisplatin; irinotecan; gemcitabine; biliary cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Gemcitabine; Cisplatin; Irinotecan
• Other Study ID Numbers: GAMBIT201201