Gemcitabine With/Out Capecitabine in Locally Advanced, Unresectable, or Metastatic Biliary Cancer

NCT00658593 | Terminated Phase 3 DMC

• 3 other identifiers: BI1CAN-NCIC-BI1CDR0000592854
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 8

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether gemcitabine is more effective when given together with or without capecitabine in treating patients with biliary cancer. PURPOSE: This randomized phase III trial is studying giving gemcitabine together with capecitabine to see how well it works compared with giving gemcitabine alone in treating patients with locally advanced, unresectable, or metastatic biliary cancer.

Conditions

Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Liver Cancer

Keywords

adenocarcinoma of the extrahepatic bile duct; unresectable extrahepatic bile duct cancer; recurrent extrahepatic bile duct cancer; adenocarcinoma of the gallbladder; adenocarcinoma with squamous metaplasia of the gallbladder; unresectable gallbladder cancer; recurrent gallbladder cancer; liver and intrahepatic biliary tract cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival

Secondary Outcomes (7)

• Progression-free survival

• Response rates (complete response [CR] and partial response [PR])

• Rate of stable disease (SD)

• Rate of disease control (CR, PR, and SD)

• Response duration

Study Arms (2)

GEMCAP

ACTIVE COMPARATOR

Gemcitabine 1000mg/m2 IV days 1 and 8 ever 21 days; Capecitabine 650mg/m2 PO BID days 1-14 every 21 days.

Drug: capecitabine; Drug: gemcitabine hydrochloride; Procedure: quality-of-life assessment

Gemcitabine Alone

ACTIVE COMPARATOR

Gemcitabine 1000mg/m2 IV days 1, 8 and 15 every 28 days

Drug: gemcitabine hydrochloride; Procedure: quality-of-life assessment

Interventions

capecitabine DRUG

GEMCAP

gemcitabine hydrochloride DRUG

GEMCAP; Gemcitabine Alone

quality-of-life assessment PROCEDURE

GEMCAP; Gemcitabine Alone

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically proven adenocarcinoma of the biliary tree (intra- and extra-hepatic biliary ducts or gallbladder) * Locally advanced, unresectable, or metastatic disease * Patients with pathologically confirmed metastatic adenocarcinoma consistent with biliary primary with clinical documentation of gallbladder or biliary tree involvement and no evidence of another primary adenocarcinoma are eligible * Must have evidence of disease but measurable disease is not required * Chest x-ray and/or CT scan of the chest, CT scan or MRI of the abdomen, and other radiological examination to document all disease sites have been done within 28 days prior to randomization * No repeat scan needed if a negative scan was performed within 35 days prior to randomization * Patients who have only one site of disease located inside a previous radiotherapy field are eligible * Lesions within a previous radiotherapy field may be considered measurable if documented ≥ 20% increase in size * If the lesion size increase has not been documented since the completion of radiotherapy, and the lesion is still present (i.e. not CR), the lesion is considered evaluable for this trial * Patients with biliary duct obstruction are eligible provided all of the following criteria are met: * Treatable, clinically relevant obstruction * Obstruction has been relieved by internal endoscopic drainage/stenting, palliative bypass surgery or percutaneous drainage prior to trial entry * No ampullary carcinomas (i.e., arising from the ampulla of Vater) * No central nervous system (CNS) metastases, including active, progressive brain or leptomeningeal metastases * Patients with focal neurological symptoms must have had a CT scan to rule out CNS metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Minimum life expectancy of 12 weeks * Able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in one of the validated languages * Must be able to swallow and retain oral medication * Hemoglobin \> 90 g/L * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Total bilirubin \< 3 times upper limit of normal(ULN) * AST and/or ALT ≤ 5 times ULN * Liver function tests stable and \< 3 times ULN * Serum creatinine \< 160 µmol/L OR creatinine clearance \> 60 mL/min * Negative pregnancy test * Fertile patients and their partners must agree to use adequate contraception prior to study entry, throughout the study, and for a period of 4 weeks after cessation of protocol therapy * Patients must be accessible for treatment and follow-up * No known dihydropyrimidine dehydrogenase deficiency * No known hypersensitivity to gemcitabine or capecitabine * No other active medical condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy, including, but not limited to, any of the following: * Unstable angina * Uncontrolled arrhythmia * Heart failure * No other condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol * No other malignancies except adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for \> 5 years PRIOR CONCURRENT THERAPY: * No prior chemotherapy for advanced or metastatic disease unless used in the following circumstances: * Fluorouracil or gemcitabine given concurrently with radiotherapy as a radiosensitizer, completed more than 3 months prior to randomization * Fluorouracil given as adjuvant treatment following surgery, completed at least 1 year prior to randomization * No major surgery within 4 weeks of randomization * No prior treatment with another investigational agent within 2 weeks of randomization * At least 4 weeks from randomization since completion of prior radiotherapy and recovered * Patients may be randomized within the required 4 weeks if short course (\< 5 fractions) of non-myelosuppressive radiotherapy was given * Concurrent palliative radiation to a known site of bone metastasis allowed provided that the criteria for disease progression are otherwise not met * No other concurrent anti-cancer therapy (cytotoxic, biological/immunotherapy or radiotherapy other than for known bone metastases as specified above) * No other concurrent investigational drug therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead

Study Sites (8)

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute at University of Alberta

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

British Columbia Cancer Agency - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

St. Catharines General Hospital at Niagara Health System

St. Catharines, Ontario, L2R 7C6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Charles Lemoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

MeSH Terms

Conditions

Bile Duct Neoplasms; Gallbladder Neoplasms; Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Capecitabine; Gemcitabine

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jennifer Knox, MD

  Princess Margaret Hospital, Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2008
• First Posted: April 15, 2008
• Study Start: October 10, 2008
• Primary Completion: May 11, 2010
• Study Completion: January 18, 2011
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (8)