Clinical trial NCT01530503: Second Line Therapy in Advanced Biliary Tract Cancer
Official title: A Randomized Phase II Trial of Second Line Therapy in Advanced Biliary Tract Cancer: Capecitabine or Capecitabine Plus Mitomycin C
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Biliary Tract Cancer
Keywords: biliary tract cancer
advanced disease
chemotherapy
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Regione Lombardia
First posted: 2012-02-10
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 6 month PFS
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: median OS (up to 2 years)
Other outcomes:
Locations:
city: Fabriano
country: Italy
facility: ASUR zona territoriale N. 6 FABRIANO
state: Ancona
city: Cefalù
country: Italy
facility: Fondazione Istituto San Raffaele G. Giglio
state: Palermo
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I - G.M. Lancisi - G Salesi
city: Bergamo
country: Italy
facility: A.O. Ospedali Riuniti
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi
city: Candiolo (Torino)
country: Italy
facility: Fondazione Piemontese Per la Ricerca sul Cancro
city: Catania
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Padova
country: Italy
facility: Istituto Oncologico Veneto I.R.C.C.S.
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
city: Potenza
country: Italy
facility: Azienda Ospedaliera Regionale San Carlo
city: Roma
country: Italy
facility: Istituto Nazionale dei Tumori Regina Elena
city: Saronno (VA)
country: Italy
facility: Ospedale Generale Provinciale
city: Torino
country: Italy
facility: Azienda Ospedaliera Universitaria San Giovanni Battista di Torino
city: Udine
country: Italy
facility: Azienda Ospedaliero Universitaria Santa Maria della Misericordia
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata
Study officials:
affiliation: Ospedale San Raffaele (Milan, Italy)
name: stefano cereda, MD
role: PRINCIPAL_INVESTIGATOR
References: