Gemcitabine and Cisplatin Plus Sorafenib in Patients With Advanced Biliary Tract Carcinomas Naive to Systemic Therapy

Phase 2

Completed

Conditions: Extrahepatic Bile Duct Cancer
Gallbladder Cancer

Interventions: Drug: Gemcitabine
Drug: Cisplatin
Drug: Sorafenib

Registration Number: NCT00919061

Lead Sponsor: Memorial Sloan Kettering Cancer Center

Brief Summary: The purpose of this study is to test an investigational combination of drugs for bile duct or gallbladder cancers.

Gemcitabine and cisplatin are two forms of chemotherapy commonly used in combination to treat bile duct and gallbladder cancers. We are looking to improve treatment results. We will attempt to do so by adding sorafenib (a type of monoclonal antibody) to your treatment plan. Sorafenib acts by attaching to blocking specific targets on cells. These targets may help the cancer cells grow and divide. This study will help answer the question of whether sorafenib is a helpful drug in patients with bile duct or gallbladder cancers when given with gemcitabine and cisplatin.

This study is a phase 2 study. The purpose of a phase 2 study is to find out what effects, good and/or bad, sorafenib in combination with gemcitabine and cisplatin has on advanced bile duct and gallbladder cancers.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 39

Inclusion Criteria

Histologically / cytologically verified, non-resectable, recurrent, or metastatic biliary tract carcinoma including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder carcinoma. Combined cholangiocarcinoma and hepatocellular carcinoma is allowed.Patients must have uni-dimensionally measurable disease by x-ray, CT scan, MRI scan or physical examination.
KPS ≥ 80%
Age ≥ 18 years
Adequate bone marrow function defined as: Hb ≥ 8 g/dl, ANC ≥ 1.5 K/mcL, Platelets ≥ 100 K/mcL
Adequate renal function defined as Serum creatinine < 2.0 mg/dl and calculated creatinine clearance ≥ 60 ml/min using the formula:
Cockcroft-Gault formula:

Cockcroft-Gault Formula - MALES CrCl = (140 - age[years]) (body wt[kg]) (72) (serum creatinine [mg/dL]) Cockcroft-Gault Formula - FEMALES CrCl = 0.85 x male value

If calculated creatinine clearance is not within range using the above formula, then measured levels from 24-hour urine collection may be used to calculate the creatinine clearance.
Adequate hepatic function defined as total bilirubin ≤ 2 mg/dl, ALT/AST/ ≤ 3 x ULN (≤ 5 if liver metastases). Patients with biliary obstruction can join if bilirubin corrects to required limit after adequate biliary drainage.
PT/INR ≤ 1.7 and PTT ≤ 1.5 x ULN, unless the patient is receiving anti-coagulation therapy with agents such as warfarin or heparin
Patients who have received prior local therapy, i.e. embolization, radiation therapy, etc. (except for chemoembolization) are eligible provided that measurable disease falls outside the treatment field or within the field but has shown an increase of ≥20% in the size. Prior local therapy must be completed at least 4 weeks prior to the baseline scan
Women of childbearing potential must have a negative pregnancy test.
Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. Patients are encouraged to continue barrier method contraception for two years or longer after treatment.
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Any previous chemotherapy, biologic therapy, or investigational agent, except for 5-FU or gemcitabine given as adjuvant therapy as single agents and/or as radio-sensitizing agents. Patient must have completed adjuvant therapy no less than six months prior to accrual. Patients with previous significant allergic hypersensitivity to gemcitabine are excluded.
Evidence of another active cancer that may influence patient outcome as determined by the Principal Investigator, except for non-melanoma skin carcinoma, melanoma in-situ, in-situ carcinoma of the cervix curatively treated, treated superficial bladder cancer, and adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is non-detectable.
Known brain metastases
History of primary central nervous system tumors or brain metastases, and/or seizures not well controlled with standard medical therapy.
Uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations that would limit compliance with study requirements.
Known HIV positive patient
Blood Pressure of > 150/100 mm Hg
Significant cardiovascular disease including congestive heart failure (New York Heart Association Class II or higher) or active angina pectoris.
History of a myocardial infarction within 6 months.
History of a stroke or transient ischemic attack within 6 months.
Clinically significant peripheral vascular disease.
Evidence of bleeding diathesis or coagulopathy.
Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks.
Uncontrolled infection.
Known or suspected allergy to sorafenib or any agent given in the course of this trial.
Pregnant (positive pregnancy test)
Breast-feeding should be discontinued if the mother is to be treated on clinical trial.
Serious non-healing wound, ulcer, or bone fracture
Use of St. John's Wort or rifampin (rifampicin)
Any condition that impairs patient's ability to swallow whole pills
Any malabsorption problem

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gemcitabine and Cisplatin plus Sorafenib	Cisplatin	This is a non-randomized, open label, single institution, phase II study of gemcitabine and cisplatin plus sorafenib for the treatment of patients with advanced or biliary tract carcinomas naïve to systemic therapy.
Gemcitabine and Cisplatin plus Sorafenib	Sorafenib	This is a non-randomized, open label, single institution, phase II study of gemcitabine and cisplatin plus sorafenib for the treatment of patients with advanced or biliary tract carcinomas naïve to systemic therapy.
Gemcitabine and Cisplatin plus Sorafenib	Gemcitabine	This is a non-randomized, open label, single institution, phase II study of gemcitabine and cisplatin plus sorafenib for the treatment of patients with advanced or biliary tract carcinomas naïve to systemic therapy.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival	6 months	Progression free survival will be calculated from study entry to documented disease progression, death from any cause, or drop out due to toxicity, whichever occurs first.
Median PFS	6 mos	Progression free survival will be calculated from study entry to documented disease progression, death from any cause, or drop out due to toxicity, whichever occurs first.

Secondary Outcome Measures