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A Phase III Study of Gemcitabine Plus Capecitabine (GEMCAP) Versus Gemcitabine Alone in Advanced Biliary Cancer

Phase 3
18 Years
Not Enrolling
Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Liver Cancer

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Trial Information

A Phase III Study of Gemcitabine Plus Capecitabine (GEMCAP) Versus Gemcitabine Alone in Advanced Biliary Cancer



- 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.


- 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

- 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.

Inclusion Criteria


- 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


- 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


- No prior chemotherapy for advanced or metastatic disease unless used in the following

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Safety Issue:


Principal Investigator

Jennifer Knox, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Princess Margaret Hospital, Canada


United States: Federal Government

Study ID:




Start Date:

March 2008

Completion Date:

January 2011

Related Keywords:

  • Extrahepatic Bile Duct Cancer
  • Gallbladder Cancer
  • Liver Cancer
  • 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
  • Liver Neoplasms
  • Gallbladder Neoplasms
  • Bile Duct Neoplasms