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

Primary Purpose

Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Liver Cancer

Status
Terminated
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
capecitabine
gemcitabine hydrochloride
quality-of-life assessment
Sponsored by
NCIC Clinical Trials Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Extrahepatic Bile Duct Cancer focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Tom Baker Cancer Centre - Calgary
  • Cross Cancer Institute at University of Alberta
  • BCCA - Fraser Valley Cancer Centre
  • British Columbia Cancer Agency - Vancouver Cancer Centre
  • Ottawa Hospital Regional Cancer Centre - General Campus
  • St. Catharines General Hospital at Niagara Health System
  • Princess Margaret Hospital
  • Hopital Charles Lemoyne

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

GEMCAP

Gemcitabine Alone

Arm Description

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

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

Outcomes

Primary Outcome Measures

Overall survival

Secondary Outcome Measures

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
Quality of Life
Toxicity

Full Information

First Posted
April 12, 2008
Last Updated
August 3, 2023
Sponsor
NCIC Clinical Trials Group
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1. Study Identification

Unique Protocol Identification Number
NCT00658593
Brief Title
Gemcitabine With/Out Capecitabine in Locally Advanced, Unresectable, or Metastatic Biliary Cancer
Official Title
A Phase III Study of Gemcitabine Plus Capecitabine (GEMCAP) Versus Gemcitabine Alone in Advanced Biliary Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
due to poor accrual
Study Start Date
October 10, 2008 (Actual)
Primary Completion Date
May 11, 2010 (Actual)
Study Completion Date
January 18, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NCIC Clinical Trials Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
OBJECTIVES: Primary To compare overall survival (OS) rates in patients with locally advanced, unresectable or metastatic biliary tree cancer treated with combined gemcitabine hydrochloride and capecitabine vs. gemcitabine hydrochloride alone. Secondary To compare progression-free survival (PFS) in this patient group. To compare response rates (complete response [CR] and partial response [PR]) in this patient group. To compare stable disease (SD) rates in this patient group. To compare rate of disease control (CR, PR and SD) in this patient group. To estimate and compare response duration in this patient group. To compare the effects of these treatments on measures of quality of life in this patient group using the EORTC QLQ-C30. To compare the nature, severity and frequency of toxicities between the two arms. OUTLINE: This is a multicenter study. Patients are stratified according to tumour type (cholangiocarcinoma vs. gallbladder or biliary unknown), ECOG performance status (0-1 vs. 2), extent of disease (locally advanced vs. metastatic), and treatment center. Patients are randomized to 1 of 2 treatment arms. Arm I (Gemcitabine hydrochloride and capecitabine): Patients receive gemcitabine hydrochloride IV on days 1 and 8 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Arm II (Gemcitabine hydrochloride alone): Patients receive gemcitabine hydrochloride IV on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 12 weeks after randomization and 4 weeks after completion of study treatment. After completion of study treatment, patients are followed at 4 weeks and then every 12 weeks thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GEMCAP
Arm Type
Active Comparator
Arm Description
Gemcitabine 1000mg/m2 IV days 1 and 8 ever 21 days; Capecitabine 650mg/m2 PO BID days 1-14 every 21 days.
Arm Title
Gemcitabine Alone
Arm Type
Active Comparator
Arm Description
Gemcitabine 1000mg/m2 IV days 1, 8 and 15 every 28 days
Intervention Type
Drug
Intervention Name(s)
capecitabine
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Intervention Type
Procedure
Intervention Name(s)
quality-of-life assessment
Primary Outcome Measure Information:
Title
Overall survival
Secondary Outcome Measure Information:
Title
Progression-free survival
Title
Response rates (complete response [CR] and partial response [PR])
Title
Rate of stable disease (SD)
Title
Rate of disease control (CR, PR, and SD)
Title
Response duration
Title
Quality of Life
Title
Toxicity

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer Knox, MD
Organizational Affiliation
Princess Margaret Hospital, Canada
Official's Role
Study Chair
Facility Information:
Facility Name
Tom Baker Cancer Centre - Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Cross Cancer Institute at University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
BCCA - Fraser Valley Cancer Centre
City
Surrey
State/Province
British Columbia
ZIP/Postal Code
V3V 1Z2
Country
Canada
Facility Name
British Columbia Cancer Agency - Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Ottawa Hospital Regional Cancer Centre - General Campus
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
St. Catharines General Hospital at Niagara Health System
City
St. Catharines
State/Province
Ontario
ZIP/Postal Code
L2R 7C6
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Hopital Charles Lemoyne
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2H1
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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