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Second Line Therapy in Advanced Biliary Tract Cancer (BIT-2)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by IRCCS San Raffaele.
Recruitment status was  Recruiting
Regione Lombardia
Information provided by (Responsible Party):
stefano cereda, IRCCS San Raffaele Identifier:
First received: February 3, 2012
Last updated: February 9, 2012
Last verified: February 2012

The purpose of this study is to assess the therapeutic activity of capecitabine alone or in combination with mitomycin C as second-line therapy in patients with advanced/metastatic biliary adenocarcinoma in progression after gemcitabine and platinum compounds

Condition Intervention Phase
Biliary Tract Cancer
Drug: capecitabine and mitomycin
Drug: Capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Second Line Therapy in Advanced Biliary Tract Cancer: Capecitabine or Capecitabine Plus Mitomycin C

Resource links provided by NLM:

Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 6 month PFS ] [ Designated as safety issue: Yes ]
    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.

Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: median OS (up to 2 years) ] [ Designated as safety issue: Yes ]

    the time from the date of randomization to the date of death from any cause

    All patients will be followed for survival every 3 months up to 2 years after the end of treatment

Estimated Enrollment: 52
Study Start Date: November 2011
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: capecitabine
oral capecitabine 2000 mg/m2 day 1-14 in two divided doses taken with food
Drug: Capecitabine

oral capecitabine 2000 mg/m2 day 1-14 in two divided doses taken with food.

Cycles will be repeated in both arms every 3 weeks till progression, unacceptable toxicity, medical decision or patient's refusal or for a maximum of 6 months

Other Name: capecitabine
Experimental: capecitabine plus mitomycin
oral capecitabine 2000 mg/m2 day 1-14 in two divided doses taken with food plus bolus IV infusion Mitomycin 6 mg/m2 day 1
Drug: capecitabine and mitomycin

oral capecitabine 2000 mg/m2 day 1-14 in two divided doses taken with food plus bolus IV infusion mitomycin C 6 mg/m2 day 1.

Cycles will be repeated in both arms every 3 weeks till progression, unacceptable toxicity, medical decision or patient's refusal or for a maximum of 6 months

Other Names:
  • capecitabine
  • mitomycin

Detailed Description:

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.


Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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); SGOT e SGPT ≤ 2.5 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01530503

Contact: stefano cereda, MD +39 0226437626

ASUR zona territoriale N. 6 FABRIANO Not yet recruiting
Fabriano, Ancona, Italy
Contact: rosa rita silva, MD         
Fondazione Istituto San Raffaele G. Giglio Not yet recruiting
Cefalù, Palermo, Italy
Contact: livio blasi, MD         
Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I - G.M. Lancisi - G Salesi Not yet recruiting
Ancona, Italy
Contact: stefano cascinu, MD         
A.O. Ospedali Riuniti Not yet recruiting
Bergamo, Italy
Contact: roberto la bianca, MD         
Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi Recruiting
Bologna, Italy
Contact: giovanni brandi, MD         
Fondazione Piemontese Per la Ricerca sul Cancro Not yet recruiting
Candiolo (Torino), Italy, 10060
Contact: massimo aglietta, MD         
Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi Not yet recruiting
Catania, Italy
Contact: stefano cordio, MD         
Ospedale San Raffaele Recruiting
Milan, Italy, 20132
Contact: stefano cereda, MD    +39 0226437626   
Sub-Investigator: michele reni, MD         
Istituto Oncologico Veneto I.R.C.C.S. Recruiting
Padova, Italy
Contact: vittorina zagonel, MD         
Azienda Ospedaliero-Universitaria Pisana Not yet recruiting
Pisa, Italy
Contact: alfredo falcone, MD         
Azienda Ospedaliera Regionale San Carlo Not yet recruiting
Potenza, Italy
Contact: domenico bilancia, MD         
Istituto Nazionale dei Tumori Regina Elena Not yet recruiting
Roma, Italy
Contact: michele milella, MD         
Ospedale Generale Provinciale Not yet recruiting
Saronno (VA), Italy
Contact: claudio verusio, MD         
Azienda Ospedaliera Universitaria San Giovanni Battista di Torino Not yet recruiting
Torino, Italy
Contact: libero ciuffreda, MD         
Azienda Ospedaliero Universitaria Santa Maria della Misericordia Not yet recruiting
Udine, Italy, 33100
Contact: giuseppe aprile, MD         
Azienda Ospedaliera Universitaria Integrata Not yet recruiting
Verona, Italy
Contact: giampaolo tortora, MD         
Sponsors and Collaborators
IRCCS San Raffaele
Regione Lombardia
Principal Investigator: stefano cereda, MD Ospedale San Raffaele (Milan, Italy)
  More Information

No publications provided

Responsible Party: stefano cereda, Principal Investigator, IRCCS San Raffaele Identifier: NCT01530503     History of Changes
Other Study ID Numbers: 2011-002002-70
Study First Received: February 3, 2012
Last Updated: February 9, 2012
Health Authority: Italy: National Institute of Health

Keywords provided by IRCCS San Raffaele:
biliary tract cancer
advanced disease

Additional relevant MeSH terms:
Biliary Tract Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Digestive System Neoplasms
Neoplasms by Site
Alkylating Agents
Antibiotics, Antineoplastic
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on February 27, 2015