A Study of Combination of Gemcitabine, Oxaliplatin (GEMOX)-Sorafenib in Patients With Advanced Biliary Tract Cancer

NCT ID: NCT00955721

Last Updated: 2018-01-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2014-07-31

Brief Summary

The purpose of this study is to build on the efficacy of the GEMOX regimen by adding Sorafenib in the treatment of Biliary Tract Cancer. Since there is no data on the combination of these three agents, the investigators plan to evaluate the safety in a run-in phase I portion in order to define the recommended phase II dose (RPTD). The phase II trial will enroll 40 patients at the RPTD level within 2 years in order to provide a preliminary estimate of progression-free survival (primary endpoint of the trial) in the target population.

Detailed Description

The purpose of this study is to build on the efficacy of the GEMOX regimen by adding Sorafenib in the treatment of Biliary Tract Cancer. Since there are no data on the combination of these three agents, the investigators plan to evaluate the safety in a run-in phase I portion in order to define the recommended phase II dose (RPTD). The phase II trial will enroll 40 patients at the RPTD level within 2 years in order to provide a preliminary estimate of progression-free survival (primary endpoint of the trial) in the target population.

Conditions

Cholangiocarcinoma; Biliary Tract Cancer; Gallbladder Cancer

Study Design

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

Study Groups

Phase 1: GEMOX + Sorafenib

Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib.

• Gemcitabine: 1000 or 750 mg/m2, IV, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
• Oxaliplatin: 100 or 75 mg/m2, IV, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
• Sorafenib: 200 mg, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.

Oxaliplatin

Intervention Type: DRUG

Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.

Sorafenib

Intervention Type: DRUG

Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.

Phase 2 - RPTD GEMOX + Sorafenib

Recommended Phase Two Dose (RPTD) of Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:

• Gemcitabine: Recommended Phase II Dose determined from Phase I, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
• Oxaliplatin: Recommended Phase II Dose determined from Phase I, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
• Sorafenib: Recommended Phase II Dose determined from Phase I, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.

Oxaliplatin

Intervention Type: DRUG

Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.

Sorafenib

Intervention Type: DRUG

Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.

Interventions

Gemcitabine

Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.

Intervention Type: DRUG

Oxaliplatin

Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.

Intervention Type: DRUG

Sorafenib

Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.

Intervention Type: DRUG

Other Intervention Names

Gemzar; Eloxatin; BAY 43-9006

Eligibility Criteria

Inclusion Criteria

• Age >= 18 years
• Histologically or cytologically confirmed biliary tract or gallbladder carcinoma
• Any stage of disease is allowed but the patients must not be candidates for curative resection
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 in Ph I
• ECOG performance status 0-2 in Ph II. Patients with ECOG PS of 2 will only be enrolled if they will comprise at most 25% of the total accruals. This will be monitored in real time to ensure that at any point during accrual, PS 2 patients will comprise <= 25% of the total accruals
• Patients must have normal organ and marrow function as defined below within 14 days of study entry:

• Absolute neutrophil count >= 1,500 cells/mm3
• Platelet count >= 60,000/mm3
• Creatinine < 1.5 upper limit of normal (ULN).
• Aspartate transaminase (AST) and Alanine transaminase (ALT) <= 2.5 x ULN.
• Bilirubin <= 3.0 mg/dl
• International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin will not be candidates for the trial. Patients on anticoagulation with low molecular weight or heparinoids are protocol candidates.
• Any number of previous lines of chemotherapy is allowed for the phase I portion
• During the phase II trial, no prior chemotherapy for inoperable or metastatic disease is allowed except 5-FU or Capecitabine as radiosensitizers. Prior adjuvant chemotherapy is allowed.
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
• Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.
• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
• Life expectancy of greater than 12 weeks

Exclusion Criteria

• Investigational agents within 28 days prior to Day 1 of study
• Chemotherapy within 4 weeks prior to Day 1 of study
• Nitrosoureas, mitomycin-C within 6 weeks prior to Day 1 of study.
• Prior treatment with sorafenib, gemcitabine or oxaliplatin
• Prior history of peripheral neuropathy > Grade 1 (e.g., diabetic neuropathy)
• Pregnant or breast-feeding female
• Patients with a history of allergic reactions or sensitivity attributed to compounds of similar chemical or biologic composition to sorafenib, oxaliplatin or gemcitabine
• Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)
• Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
• Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
• Known human immunodeficiency virus (HIV) infection and Hepatitis B and Hepatitis C.
• Active clinically serious infection > CTCAE Grade 2.
• Arterial thrombotic/embolic events like myocardial infarct and cerebrovascular accident including transient ischemic attacks within the past 6 months.
• Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
• Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
• Serious non-healing wound, ulcer, or bone fracture.
• Evidence or history of bleeding diathesis or coagulopathy
• Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
• Use of St. John's Wort or rifampin (rifampicin).
• Any medical condition, which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities

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

Sponsors

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Peter Hosein

Assistant Professor of Clinical

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter Hosein, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Countries

United States

Other Identifiers

SCCC-2009003

Identifier Type: OTHER

Identifier Source: secondary_id

20090256

Identifier Type: -

Identifier Source: org_study_id