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A Randomized Phase II Trial of Second Line Therapy in Advanced Biliary Tract Cancer: Capecitabine or Capecitabine Plus Mitomycin C

Phase 2
18 Years
75 Years
Open (Enrolling)
Biliary Tract Cancer

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Trial Information

A Randomized Phase II Trial of Second Line Therapy in Advanced Biliary Tract Cancer: Capecitabine or Capecitabine Plus Mitomycin C

Biliary tract adenocarcinoma is an uncommon tumor with a poor prognosis and a median overall
survival (OS) rarely exceeding 6 months. Less than 25% of patients are resectable at
diagnosis and, even in this subset of patients, relapse rate is high. An improvement of OS
and quality of life for patients receiving chemotherapy versus best supportive care was
demonstrated in advanced disease. Recently, cisplatin and gemcitabine combination was
identified as the new standard first-line chemotherapy, yielding a median progression free
survival (PFS) and median OS of 8.5 and 11.7 months, respectively. Despite the outcome
improvement, disease progression is a constant and approximately half of patients failing
upfront treatment has a good performance status and are willing to undergo further
treatment. No standard salvage chemotherapy regimen has been identified. Clinical trials are
difficult to perform due to the rarity and heterogeneity of these tumors and to the lack of
interest of the pharmaceutical industry. Fluoropyrimidines and mitomycin C have been
considered the basis of palliative chemotherapy for a long time. The investigators decided
to explore the activity, in terms of PFS, of capecitabine alone or combined with mitomycin C
as second-line therapy in patients with pathological diagnosis of advanced biliary tract
cancer and progressive disease after gemcitabine and cisplatin, by means of an open label
randomized multicentric phase II trial.

Inclusion Criteria:

1. Signed and dated IRB/IEC-approved Informed Consent.

2. Cytological or histological diagnosis of locally advanced or metastatic
adenocarcinoma of the biliary tract (Ampulla of Vater, gallbladder, intra or
extra-hepatic biliary ducts).

3. Disease progressing after first-line chemotherapy with gemcitabine and platinum
analogs (only one prior systemic therapy allowed).

4. Age 18-75 years

5. Karnofsky Performance Status > 50%

6. Estimated life expectancy of at least 3 months.

7. Negative pregnancy test (if female in reproductive years).

8. Adequate bone marrow, liver and kidney function: leukocyte > 3500/mm3; absolute
neutrophil count (ANC) > 1500/mm3; platelet count > 100000/mm3; hemoglobin > 10 g/dl;
creatinine < 1.5 mg/dL; total bilirubin ≤ 1.5 x upper limit of normal range (ULN);

9. At the time of start of treatment, at least 2 weeks must have elapsed since
completion of prior chemotherapy, minor surgery and radiotherapy (provided that no
more than 25% of bone marrow reserve has been irradiated).

10. Resolution of all acute toxic effects of any prior chemotherapy, surgery or
radiotherapy to NCI CTC (Version 4.03) grade ≤ 1 for hematologic toxicities and ≤ 2
for non hematologic toxicities, with the exception of alopecia.

11. Able and willing to comply with scheduled visits, therapy plans, and laboratory tests
required in this protocol.

Exclusion Criteria:

1. Previous or concurrent malignancies at other sites with the exception of surgically
cured carcinoma in-site of the cervix and basal or squamous cell carcinoma of the
skin and of other neoplasm without evidence of disease at least from 5 years.

2. Known brain metastases.

3. Previous second-line or adjuvant treatment.

4. Concurrent treatment with other experimental drugs.

5. Clinically significant cardiovascular disease (including myocardial infarction,
unstable angina, symptomatic congestive heart failure, cardiac arrhythmia) ≤1 year
prior to dosing.

6. Clinically significant disease including: Cerebral Vascular Accident; other serious
underlying medical condition(s) which could impair the ability of the patient to
participate in the study.

7. History of interstitial lung disease (eg, pneumonia or pulmonary fibrosis) or
evidence of interstitial lung disease on baseline chest CT scan

8. Known positive tests for human immunodeficiency virus (HIV) infection, active
hepatitis B or hepatitis C

9. Subject who is pregnant or breast feeding

10. Woman or man of child-bearing potential not consenting to use adequate contraceptive
precautions ie. double barrier contraceptive methods (e.g., diaphragm plus condom),
or abstinence during the course of the study and for 6 months after the last study
drug administration for women, and 1 month for men

11. Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule

Type of Study:


Study Design:

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

Outcome Measure:

Progression Free Survival (PFS)

Outcome Description:

This is a multi-centre phase II, randomized study. Patients will be stratified based on disease site and stage. For the purpose of the study, PFS-6 rate will be considered the primary outcome measure. The maximum PFS-6 rate of low clinical interest is 15% and the minimum PFS-6 rate of interest is set to 35%. The target enrollment, using a type I error of 5% and a test power of 90%, will be estimated to be 26 patients per treatment arm. The regimen will be considered active if at least 8 out of first 26 evaluable patients are PFS-6.

Outcome Time Frame:

6 month PFS

Safety Issue:


Principal Investigator

stefano cereda, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ospedale San Raffaele (Milan, Italy)


Italy: National Institute of Health

Study ID:




Start Date:

November 2011

Completion Date:

July 2013

Related Keywords:

  • Biliary Tract Cancer
  • biliary tract cancer
  • advanced disease
  • chemotherapy
  • Biliary Tract Neoplasms