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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Peter Hosein, University of Miami
ClinicalTrials.gov Identifier:
NCT00955721
First received: August 6, 2009
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Cholangiocarcinoma
Biliary Tract Cancer
Gallbladder Cancer
Drug: Gemcitabine
Drug: Oxaliplatin
Drug: Sorafenib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Combination of Gemcitabine, Oxaliplatin and Sorafenib (GEMOX-Sorafenib) in Patients With Advanced Biliary Tract Cancer

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase II: Estimate overall response rate and clinical benefit rate. [ Time Frame: 9 Months ] [ Designated as safety issue: No ]
  • Phase II: Estimate overall survival [ Time Frame: Start of treatment until death ] [ Designated as safety issue: No ]
  • Phase II: Further evaluate the safety of the proposed combination [ Time Frame: 9 Months ] [ Designated as safety issue: Yes ]
  • Phase II: Explore biomarkers of response to the combination [ Time Frame: 9 Months ] [ Designated as safety issue: No ]

Estimated Enrollment: 58
Study Start Date: August 2009
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1 Drug: 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.
Drug: 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.
Drug: Sorafenib
  • 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.
Other Name: BAY 43-9006
Experimental: Phase 2 Drug: 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.
Drug: 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.
Drug: Sorafenib
  • 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.
Other Name: BAY 43-9006

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00955721

Locations
United States, Florida
University of Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Peter Hosein, MD University of Miami
  More Information

No publications provided

Responsible Party: Peter Hosein, Assistant Professor of Clinical, University of Miami
ClinicalTrials.gov Identifier: NCT00955721     History of Changes
Other Study ID Numbers: 20090256, SCCC-2009003
Study First Received: August 6, 2009
Last Updated: July 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Miami:
Cholangiocarcinoma
Biliary Tract Cancer
Gallbladder Cancer

Additional relevant MeSH terms:
Gallbladder Neoplasms
Cholangiocarcinoma
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gemcitabine
Sorafenib
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 25, 2014