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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01530503
Recruitment Status : Completed
First Posted : February 10, 2012
Last Update Posted : February 25, 2016
Regione Lombardia
Information provided by (Responsible Party):
stefano cereda, IRCCS San Raffaele

Brief Summary:
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 or disease Intervention/treatment Phase
Biliary Tract Cancer Drug: capecitabine and mitomycin Drug: Capecitabine Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : November 2011
Primary Completion Date : October 2013
Study Completion Date : October 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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

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

Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 6 month PFS ]
    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 :
  1. Overall Survival (OS) [ Time Frame: median OS (up to 2 years) ]

    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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01530503

ASUR zona territoriale N. 6 FABRIANO
Fabriano, Ancona, Italy
Fondazione Istituto San Raffaele G. Giglio
Cefalù, Palermo, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I - G.M. Lancisi - G Salesi
Ancona, Italy
A.O. Ospedali Riuniti
Bergamo, Italy
Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi
Bologna, Italy
Fondazione Piemontese Per la Ricerca sul Cancro
Candiolo (Torino), Italy, 10060
Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi
Catania, Italy
Ospedale San Raffaele
Milan, Italy, 20132
Istituto Oncologico Veneto I.R.C.C.S.
Padova, Italy
Azienda Ospedaliero-Universitaria Pisana
Pisa, Italy
Azienda Ospedaliera Regionale San Carlo
Potenza, Italy
Istituto Nazionale dei Tumori Regina Elena
Roma, Italy
Ospedale Generale Provinciale
Saronno (VA), Italy
Azienda Ospedaliera Universitaria San Giovanni Battista di Torino
Torino, Italy
Azienda Ospedaliero Universitaria Santa Maria della Misericordia
Udine, Italy, 33100
Azienda Ospedaliera Universitaria Integrata
Verona, Italy
Sponsors and Collaborators
IRCCS San Raffaele
Regione Lombardia
Principal Investigator: stefano cereda, MD Ospedale San Raffaele (Milan, Italy)

Responsible Party: stefano cereda, Principal Investigator, IRCCS San Raffaele Identifier: NCT01530503     History of Changes
Other Study ID Numbers: 2011-002002-70
First Posted: February 10, 2012    Key Record Dates
Last Update Posted: February 25, 2016
Last Verified: February 2016

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

Additional relevant MeSH terms:
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Biliary Tract Diseases
Digestive System Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antibiotics, Antineoplastic
Alkylating Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors