- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00955721
A Study of Combination of Gemcitabine, Oxaliplatin (GEMOX)-Sorafenib in Patients With Advanced Biliary Tract Cancer
December 3, 2017 updated by: Peter Hosein, University of Miami
A Phase I/II Study of Combination of Gemcitabine, Oxaliplatin and Sorafenib (GEMOX-Sorafenib) in Patients With Advanced Biliary Tract Cancer
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.
Study Overview
Status
Terminated
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
9
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Florida
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Miami, Florida, United States, 33136
- University of Miami
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase 1: GEMOX + Sorafenib
Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib.
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Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
Other Names:
Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
Other Names:
Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
Other Names:
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Experimental: Phase 2 - RPTD GEMOX + Sorafenib
Recommended Phase Two Dose (RPTD) of Gemcitabine and Oxaliplatin (GEMOX) and Sorafenib:
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Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops.
Other Names:
Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
Other Names:
Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I: 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
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Establish the recommended phase II dose (RPTD) of the combination of sorafenib and GEMOX in patients with advanced biliary tract cancer (BTC).
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First two 14-day Phase I cycles
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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
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Rate of study participants achieving progression-free survival at 9 months post-initiation of study therapy at RPTD.
Progression-Free Survival (PFS) is defined as the time elapsed from the start of treatment to the date of documented progression or death, whichever comes first.
For surviving patients without progression who begin alternative treatment, PFS will be censored at the last date of documented progression-free status prior to starting alternative treatment.
Similarly, losses to follow up will be censored at the last date of documented progression-free status.
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9 Months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase II: Estimate Overall Response Rate and Clinical Benefit Rate.
Time Frame: About 9 Months
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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).
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About 9 Months
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Phase II: Estimate Overall Survival
Time Frame: Start of treatment until death or date of last contact
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Overall survival is defined as the time elapsed from the start of treatment until death.
For surviving patients, follow-up will be censored at the date of last contact.
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Start of treatment until death or date of last contact
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Phase II: Further Evaluate the Safety of the Proposed Combination
Time Frame: About 9 Months
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Rate of study participants experiencing toxicity after receiving study therapy at the recommended Phase 2 Dose (RPTD).
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About 9 Months
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Phase II: Explore Biomarkers of Response to the Combination
Time Frame: Baseline, Day 1 of Cycle 2 and subsequent cycles, about 9 Months
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A study of the correlation between biomarker levels and response to RPTD study therapy.
Blood samples for biomarker analysis are collected at baseline and on day 1 of Cycles 2 onward
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Baseline, Day 1 of Cycle 2 and subsequent cycles, about 9 Months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Peter Hosein, MD, University of Miami
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2009
Primary Completion (Actual)
July 1, 2014
Study Completion (Actual)
July 1, 2014
Study Registration Dates
First Submitted
August 6, 2009
First Submitted That Met QC Criteria
August 7, 2009
First Posted (Estimate)
August 10, 2009
Study Record Updates
Last Update Posted (Actual)
January 3, 2018
Last Update Submitted That Met QC Criteria
December 3, 2017
Last Verified
December 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Gallbladder Diseases
- Biliary Tract Diseases
- Cholangiocarcinoma
- Biliary Tract Neoplasms
- Gallbladder Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protein Kinase Inhibitors
- Gemcitabine
- Sorafenib
- Oxaliplatin
Other Study ID Numbers
- 20090256
- SCCC-2009003 (Other Identifier: UM/Sylvester Comprehensive Cancer Center)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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