Adjuvant Chemotherapy vs no Chemotherapy for Patients With GallBllader Carcinoma

NCT ID: NCT02778308

Last Updated: 2021-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2018-12-31

Brief Summary

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

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.

Conditions

Gallbladder Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

chemotherapy group

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

Group Type: ACTIVE_COMPARATOR

Gemcitabine + Cisplatin

Intervention Type: DRUG

Day 1 and day 8 Gemcitabine Day 1 cisplatin

control group

follow up

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Gemcitabine + Cisplatin

Day 1 and day 8 Gemcitabine Day 1 cisplatin

Intervention Type: DRUG

Other Intervention Names

GemCis

Eligibility Criteria

Inclusion Criteria

1. T1b and above adenocarcinoma of gall bladder

2. Patients undergoing curative resection

3. Incidentally diagnosed carcinoma who have undergone curative completion radical cholecystectomy

Exclusion Criteria

1. T1a tumors

2. Patients with metastatic disease

3. Patients unfit to undergo chemotherapy

4. Patients unwilling to undergo the trial

5. Patients with double cancers

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Govind Ballabh Pant Institute of Postgraduate Medical Education and Research

OTHER_GOV

Sponsor Role: lead

Responsible Party

Sundeep Singh Saluja

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pramod K Mishra, Phd

Role: STUDY_CHAIR

GIPMER

Kishore Singh, MD

Role: STUDY_DIRECTOR

Lok Nayak Hospital

Locations

GIPMER

New Delhi, , India

Countries

India

References

1. Perkin DM, Whelan SL, Ferlay J, Raymond L, Young J. Cancer incidence in five continents. Vol VII, Lyon, France: International Agency for Research on Cancer Scientific Publication No. 143, 1997.

Reference Type: BACKGROUND

Shukla VK, Khandelwal C, Roy SK, Vaidya MP. Primary carcinoma of the gall bladder: a review of a 16-year period at the University Hospital. J Surg Oncol. 1985 Jan;28(1):32-5. doi: 10.1002/jso.2930280109.

Reference Type: BACKGROUND

PMID: 3968886 (View on PubMed)

Hamrick RE Jr, Liner FJ, Hastings PR, Cohn I Jr. Primary carcinoma of the gallbladder. Ann Surg. 1982 Mar;195(3):270-3. doi: 10.1097/00000658-198203000-00005.

Reference Type: BACKGROUND

PMID: 7059239 (View on PubMed)

Hawkins WG, DeMatteo RP, Jarnagin WR, Ben-Porat L, Blumgart LH, Fong Y. Jaundice predicts advanced disease and early mortality in patients with gallbladder cancer. Ann Surg Oncol. 2004 Mar;11(3):310-5. doi: 10.1245/aso.2004.03.011.

Reference Type: BACKGROUND

PMID: 14993027 (View on PubMed)

Bartlett DL, Fong Y, Fortner JG, Brennan MF, Blumgart LH. Long-term results after resection for gallbladder cancer. Implications for staging and management. Ann Surg. 1996 Nov;224(5):639-46. doi: 10.1097/00000658-199611000-00008.

Reference Type: BACKGROUND

PMID: 8916879 (View on PubMed)

Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.

Reference Type: BACKGROUND

PMID: 20375404 (View on PubMed)

Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H, Nagakawa T, Nakayama T; Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer. 2002 Oct 15;95(8):1685-95. doi: 10.1002/cncr.10831.

Reference Type: BACKGROUND

PMID: 12365016 (View on PubMed)

Saluja SS, Nekarakanti PK, Mishra PK, Srivastava A, Singh K. Prospective Randomized Controlled Trial Comparing Adjuvant Chemotherapy vs. No Chemotherapy for Patients with Carcinoma of Gallbladder Undergoing Curative Resection. J Gastrointest Surg. 2022 Feb;26(2):398-407. doi: 10.1007/s11605-021-05143-6. Epub 2021 Sep 20.

Reference Type: DERIVED

PMID: 34545545 (View on PubMed)

Other Identifiers

FI/IEC/MAMC(32)/4/2012/239

Identifier Type: -

Identifier Source: org_study_id