Second Line Therapy in Advanced Biliary Tract Cancer

Phase 2

Completed

• Conditions: Biliary Tract Cancer
• Interventions: Drug: capecitabine and mitomycin; Drug: Capecitabine

• Registration Number: NCT01530503
• Lead Sponsor: 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

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 Timeline

• Study Start: 2011-11
• Study First Submitted: 2012-02-03
• Study First Submitted QC: 2012-02-09
• Study First Posted: 2012-02-10
• Primary Completion: 2013-10
• Study Completion: 2013-10
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-24
• Last Update Posted: 2016-02-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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.

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
capecitabine plus mitomycin	capecitabine and 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
capecitabine	Capecitabine	oral capecitabine 2000 mg/m2 day 1-14 in two divided doses taken with food

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	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

Name	Time	Method
Overall Survival (OS)	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

Trial Locations

Locations (16)

Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi; 🇮🇹 Bologna, Italy

A.O. Ospedali Riuniti; 🇮🇹 Bergamo, Italy

Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I - G.M. Lancisi - G Salesi; 🇮🇹 Ancona, Italy

Fondazione Piemontese Per la Ricerca sul Cancro; 🇮🇹 Candiolo (Torino), Italy

Ospedale Generale Provinciale; 🇮🇹 Saronno (VA), Italy

Istituto Oncologico Veneto I.R.C.C.S.; 🇮🇹 Padova, Italy

Azienda Ospedaliera Regionale San Carlo; 🇮🇹 Potenza, Italy

Azienda Ospedaliero-Universitaria Pisana; 🇮🇹 Pisa, Italy

Azienda Ospedaliero Universitaria Santa Maria della Misericordia; 🇮🇹 Udine, Italy

ASUR zona territoriale N. 6 FABRIANO; 🇮🇹 Fabriano, Ancona, Italy

Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi; 🇮🇹 Catania, Italy

Ospedale San Raffaele; 🇮🇹 Milan, Italy

Azienda Ospedaliera Universitaria Integrata; 🇮🇹 Verona, Italy

Azienda Ospedaliera Universitaria San Giovanni Battista di Torino; 🇮🇹 Torino, Italy

Istituto Nazionale dei Tumori Regina Elena; 🇮🇹 Roma, Italy

Fondazione Istituto San Raffaele G. Giglio; 🇮🇹 Cefalù, Palermo, Italy