Adjuvant Chemotherapy vs no Chemotherapy for Patients With GallBllader Carcinoma

Study Overview
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Brief Summary
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Carcinoma of the gallbladder is the commonest malignancy of the biliary tract. Higher incidence has been noted in Chile, Mexico and Southwest American Indians.[1] It is the third most common malignancy in India.[2] The disease may mimic benign disease in presentation.Up to 1/3rd of patients may present with jaundice but of these only 7% will be resectable.[4] With aggressive surgical resection, actuarial 5 year survival of 83% for stage II disease and 63% for stage III have been reported.[5] Treatment of choice is complete surgical resection. The role of chemotherapy and radiotherapy is not very well documented in treatment of gallbladder cancer. Because of the propensity of gallbladder carcinoma to spread to regional lymph nodes at an early stage and the high rate of loco regional recurrence, adjuvant chemotherapy or chemo-radiotherapy seems a rational therapeutic option. Gemcitabine with or without Cisplatin has been increasingly used. In a recent paper Gemcitabine with Cisplatin was found to be more effective than gemcitabine alone and provides definite survival advantage and progression free survival.[6] An earlier randomized trial done to assess the efficacy of the adjuvant chemotherapy for the pancreato-biliary cancer reported improvement in disease free and overall 5 year survival.[7] But this study has included patients with suboptimal resection and all pancreato-biliary malignancy. In view of these observations this study is being designed to assess the efficacy of the chemotherapy in the adjuvant setting in gallbladder cancer patients who have undergone curative resections.

Detailed Description
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Carcinoma of the gallbladder is the commonest malignancy of the biliary tract. United states has an incidence of 1/100000.Higher incidence has been noted in Chile, Mexico and Southwest American Indians. It is the third most common malignancy in India. The disease may mimic benign disease in presentation. Now 78-85% of the cases may be detected preoperatively with radiological imaging. 1-3% of the carcinoma of the gall bladder may be detected incidentally. Up to 1/3rd of patients may present with jaundice but of these only 7% will be resectable. With aggressive surgical resection, actuarial 5 year survival of 83% for stage II disease and 63% for stage III have been reported. Treatment of choice is complete surgical resection. The role of chemotherapy and radiotherapy is not very well documented in treatment of gallbladder cancer. Because of the propensity of gallbladder carcinoma to spread to regional lymph nodes at an early stage and the high rate of loco regional recurrence, adjuvant chemotherapy or chemo-radiotherapy seems a rational therapeutic option. The chemotherapies are based on 5 Fluorouracil with or without radiotherapy. Gemcitabine with or without Cisplatin has been increasingly used. In a recent paper Gemcitabine with Cisplatin was found to be more effective than gemcitabine alone and provides definite survival advantage and progression free survival. An earlier randomized trial done to assess the efficacy of the adjuvant chemotherapy for the pancreato-biliary cancer reported improvement in disease free and overall 5 year survival. But this study has included patients with suboptimal resection and all pancreato-biliary malignancy. In view of these observations this study is being designed to assess the efficacy of the chemotherapy in the adjuvant setting in gallbladder cancer patients who have undergone curative resections.

Official Title
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Randomized Controlled Trial Comparing Adjuvant Chemotherapy Vs. no Chemotherapy for Patients With Carcinoma of Gallbladder Undergoing Curative Resection.

Conditions
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Gallbladder Cancer

Intervention / Treatment
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* Drug: Gemcitabine + Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T1b and above adenocarcinoma of gall bladder Patients undergoing curative resection Incidentally diagnosed carcinoma who have undergone curative completion radical cholecystectomy Exclusion Criteria: T1a tumors Patients with metastatic disease Patients unfit to undergo chemotherapy Patients unwilling to undergo the trial Patients with double cancers

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: chemotherapy group<br>6 cycles of Gemcitabine + Cisplatin as per the following schedule Injection Gemcitabine 1 gm/kgm2 intravenous over 30 min Day1 and Day8 Injection Cisplatin 70 mg/m2 intravenous on Day1 | Drug: Gemcitabine + Cisplatin<br>* Day 1 and day 8 Gemcitabine Day 1 cisplatin<br>* Other names: GemCis;|
| No Intervention: control group<br>follow up | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival | Defined as the time interval between the date of randomization and the date of disease recurrence. | From date of randomization until the date of first documented recurrence, assessed up to 100 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Defined as the time interval between the date of randomization and death from disease or unrelated cause | From date of randomization until the date of death from any cause, assessed up to 100 months | 
| Blood and lymphatic system Adverse events | As per CTCAE version 5 criteria | till 6 weeks after last cycle | 
| Gastrointestinal system Adverse events | As per CTCAE version 5 criteria | Till 6 weeks after last cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gallbladder cancer, adjuvant chemotherapy, gemcitabine