Overview

This trial is active, not recruiting.

Conditions cholangiocarcinoma, biliary tract cancer, gallbladder cancer
Treatments gemcitabine, oxaliplatin, sorafenib
Phase phase 1/phase 2
Targets RAF, FLT-3, KIT, PDGF, VEGF
Sponsor University of Miami
Start date August 2009
End date August 2014
Trial size 58 participants
Trial identifier NCT00955721, 20090256, SCCC-2009003

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
gemcitabine
Phase I: 1000 or 750 mg/m2, IV, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops. Phase II: Recommended Phase II Dose determined from Phase I, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
oxaliplatin
Phase I: 100 or 75 mg/m2, IV, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops. Phase II: Recommended Phase II Dose determined from Phase I, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
sorafenib BAY 43-9006
Phase I: 200 mg, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops. Phase II: Recommended Phase II Dose determined from Phase I, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
(Experimental)
gemcitabine
Phase I: 1000 or 750 mg/m2, IV, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops. Phase II: Recommended Phase II Dose determined from Phase I, Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
oxaliplatin
Phase I: 100 or 75 mg/m2, IV, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops. Phase II: Recommended Phase II Dose determined from Phase I, Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
sorafenib BAY 43-9006
Phase I: 200 mg, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops. Phase II: Recommended Phase II Dose determined from Phase I, Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.

Primary Outcomes

Measure
Phase I: Establish the recommended phase II dose (RPTD) of the combination of sorafenib and GEMOX in patients with advanced biliary tract cancer (BTC).
time frame: First two 14-day Phase I cycles
Phase II: Obtain an estimate of the 9-month progression-free survival rate in patients with advanced BTC receiving the RPTD of the combination sorafenib and GEMOX.
time frame: 9 Months

Secondary Outcomes

Measure
Phase II: Estimate overall response rate and clinical benefit rate.
time frame: 9 Months
Phase II: Estimate overall survival
time frame: Start of treatment until death
Phase II: Further evaluate the safety of the proposed combination
time frame: 9 Months
Phase II: Explore biomarkers of response to the combination
time frame: 9 Months

Eligibility Criteria

Male or female participants at least 18 years old.

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 - ECOG performance status 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. - AST and ALT <= 2.5 x ULN - Bilirubin <= 3.0 mg/dl - INR < 1.5 or a PT/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 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

Additional Information

Official title A Phase I/II Study of Combination of Gemcitabine, Oxaliplatin and Sorafenib (GEMOX-Sorafenib) in Patients With Advanced Biliary Tract Cancer
Principal investigator Peter Hosein, MD
Trial information was received from ClinicalTrials.gov and was last updated in July 2014.
Information provided to ClinicalTrials.gov by University of Miami.