Second Line Therapy in Advanced Biliary Tract Cancer

NCT ID: NCT01530503

Last Updated: 2016-02-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2013-10-31

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.

Conditions

Biliary Tract Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

capecitabine

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

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

capecitabine and mitomycin

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

capecitabine; mitomycin

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regione Lombardia

OTHER

Sponsor Role: collaborator

IRCCS San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

stefano cereda

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

stefano cereda, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale San Raffaele (Milan, Italy)

Locations

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

Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi

Catania, , Italy

Ospedale San Raffaele

Milan, , Italy

Istituto Oncologico Veneto I.R.C.C.S.

Padua, , 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

Azienda Ospedaliera Universitaria Integrata

Verona, , Italy

Countries

Italy

Other Identifiers

2011-002002-70

Identifier Type: -

Identifier Source: org_study_id