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

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ClinicalTrials.gov Identifier: NCT00955721
Recruitment Status : Completed
First Posted : August 10, 2009
Results First Posted : February 13, 2015
Last Update Posted : October 26, 2016
Sponsor:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Cholangiocarcinoma Biliary Tract Cancer Gallbladder Cancer Drug: Gemcitabine Drug: Oxaliplatin Drug: Sorafenib Phase 1 Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : August 2009
Primary Completion Date : July 2014


Arms and Interventions

Arm Intervention/treatment
Experimental: 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.
Drug: Gemcitabine
Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
Other Name: Gemzar
Drug: Oxaliplatin
Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
Other Name: Eloxatin
Drug: Sorafenib
Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
Other Name: BAY 43-9006
Experimental: 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.
Drug: Gemcitabine
Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
Other Name: Gemzar
Drug: Oxaliplatin
Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
Other Name: Eloxatin
Drug: Sorafenib
Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
Other Name: BAY 43-9006


Outcome Measures

Primary Outcome Measures :
  1. 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 ]
  2. 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 Outcome Measures :
  1. Phase II: Estimate Overall Response Rate and Clinical Benefit Rate. [ Time Frame: 9 Months ]
    Overall response rate [CR + PR]. Clinical Benefit Rate [Complete Response (CR) + Partial Response (PR) + Stable Disease (SD)] per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0).

  2. Phase II: Estimate Overall Survival [ Time Frame: Start of treatment until death ]
  3. Phase II: Further Evaluate the Safety of the Proposed Combination [ Time Frame: 9 Months ]
  4. Phase II: Explore Biomarkers of Response to the Combination [ Time Frame: 9 Months ]

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
  • 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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

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
First Posted: August 10, 2009    Key Record Dates
Results First Posted: February 13, 2015
Last Update Posted: October 26, 2016
Last Verified: September 2016

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

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