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

Sponsor
University of Miami (Other)
Overall Status
Terminated
CT.gov ID
NCT00955721
Collaborator
(none)
9
Enrollment
1
Location
2
Arms
59
Duration (Months)
0.2
Patients Per Site Per Month

Study Details

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
Phase 1/Phase 2

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 Design

Study Type:
Interventional
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 :
Aug 1, 2009
Actual Primary Completion Date :
Jul 1, 2014
Actual Study Completion Date :
Jul 1, 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 Names:
  • Gemzar

    • Drug: Oxaliplatin
    Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
    Other Names:
  • Eloxatin

    • Drug: Sorafenib
    Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
    Other Names:
  • 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 Names:
  • Gemzar

    • Drug: Oxaliplatin
    Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops.
    Other Names:
  • Eloxatin

    • Drug: Sorafenib
    Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
    Other Names:
  • BAY 43-9006

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Phase I: Recommended Phase II Dose (RPTD) of the Combination of Sorafenib and GEMOX in Patients With Advanced Biliary Tract Cancer (BTC). [First two 14-day Phase I cycles]

      Establish the recommended phase II dose (RPTD) of the combination of sorafenib and GEMOX in patients with advanced biliary tract cancer (BTC).

    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. [9 Months]

      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.

    Secondary Outcome Measures

    1. Phase II: Estimate Overall Response Rate and Clinical Benefit Rate. [About 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 [Start of treatment until death or date of last contact]

      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.

    3. Phase II: Further Evaluate the Safety of the Proposed Combination [About 9 Months]

      Rate of study participants experiencing toxicity after receiving study therapy at the recommended Phase 2 Dose (RPTD).

    4. Phase II: Explore Biomarkers of Response to the Combination [Baseline, Day 1 of Cycle 2 and subsequent cycles, about 9 Months]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 University of Miami Miami Florida United States 33136

    Sponsors and Collaborators

    • University of Miami

    Investigators

    • Principal Investigator: Peter Hosein, MD, University of Miami

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Peter Hosein, Assistant Professor of Clinical, University of Miami
    ClinicalTrials.gov Identifier:
    NCT00955721
    Other Study ID Numbers:
    • 20090256
    • SCCC-2009003
    First Posted:
    Aug 10, 2009
    Last Update Posted:
    Jan 3, 2018
    Last Verified:
    Dec 1, 2017
    Keywords provided by Peter Hosein, Assistant Professor of Clinical, University of Miami
    Cholangiocarcinoma
    Biliary Tract Cancer
    Gallbladder Cancer
    Additional relevant MeSH terms:
    Cholangiocarcinoma
    Biliary Tract Neoplasms
    Gallbladder Neoplasms
    Gemcitabine
    Oxaliplatin
    Sorafenib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Phase 1: GEMOX + Sorafenib Phase 2: RPTD GEMOX + Sorafenib
    Arm/Group Description 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. 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.
    Period Title: Overall Study
    STARTED 9 0
    COMPLETED 6 0
    NOT COMPLETED 3 0

    Baseline Characteristics

    Arm/Group Title Phase 1: GEMOX + Sorafenib Phase 2: RPTD GEMOX + Sorafenib Total
    Arm/Group Description 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. 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. Total of all reporting groups
    Overall Participants 9 0 9
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    NaN
    Between 18 and 65 years
    2
    22.2%
    2
    Infinity
    >=65 years
    7
    77.8%
    7
    Infinity
    Age (years) [Mean (Full Range) ]
    Mean (Full Range) [years]
    67.4
    67.4
    Sex: Female, Male (Count of Participants)
    Female
    3
    33.3%
    3
    Infinity
    Male
    6
    66.7%
    6
    Infinity
    Region of Enrollment (participants) [Number]
    United States
    9
    100%
    9
    Infinity

    Outcome Measures

    1. Primary Outcome
    Title Phase I: Recommended Phase II Dose (RPTD) of the Combination of Sorafenib and GEMOX in Patients With Advanced Biliary Tract Cancer (BTC).
    Description 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

    Outcome Measure Data

    Analysis Population Description
    A total of 9 participants were enrolled in Phase 1 of which 6 were evaluable and analyzed for this outcome measure. A recommended phase two dose (RPTD) of the combination of Sorafenib and GEMOX therapy could not be determined because dose escalation was still in progress when the study was terminated.
    Arm/Group Title Phase 1: GEMOX + Sorafenib
    Arm/Group Description 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. Gemcitabine: Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops. Oxaliplatin: Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops. Sorafenib: Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
    Measure Participants 6
    Gemcitabine
    NA
    Oxaliplatin
    NA
    Sorafenib
    NA
    2. Primary Outcome
    Title 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.
    Description 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.
    Time Frame 9 Months

    Outcome Measure Data

    Analysis Population Description
    This was an outcome measure for the Phase 2 arm. Data were not collected due to the study's termination prior to the determination of the RPTD and the opening of Phase 2.
    Arm/Group Title Phase 2: RPTD GEMOX + Sorafenib
    Arm/Group Description 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.
    Measure Participants 0
    3. Secondary Outcome
    Title Phase II: Estimate Overall Response Rate and Clinical Benefit Rate.
    Description 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).
    Time Frame About 9 Months

    Outcome Measure Data

    Analysis Population Description
    This was an outcome measure for the Phase 2 arm. Data were not collected due to the study's termination prior to the opening of Phase 2.
    Arm/Group Title Phase 2: RPTD GEMOX + Sorafenib
    Arm/Group Description 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.
    Measure Participants 0
    4. Secondary Outcome
    Title Phase II: Estimate Overall Survival
    Description 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.
    Time Frame Start of treatment until death or date of last contact

    Outcome Measure Data

    Analysis Population Description
    This was an outcome measure for the Phase 2 arm. Data were not collected due to the study's termination prior to the opening of Phase 2.
    Arm/Group Title Phase 2 - RPTD GEMOX + Sorafenib
    Arm/Group Description 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. Gemcitabine: Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops. Oxaliplatin: Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops. Sorafenib: Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
    Measure Participants 0
    5. Secondary Outcome
    Title Phase II: Further Evaluate the Safety of the Proposed Combination
    Description Rate of study participants experiencing toxicity after receiving study therapy at the recommended Phase 2 Dose (RPTD).
    Time Frame About 9 Months

    Outcome Measure Data

    Analysis Population Description
    This was an outcome measure for the Phase 2 arm. Data were not collected due to the study's termination prior to the opening of Phase 2.
    Arm/Group Title Phase 2 - RPTD GEMOX + Sorafenib
    Arm/Group Description 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. Gemcitabine: Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops. Oxaliplatin: Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops. Sorafenib: Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
    Measure Participants 0
    6. Secondary Outcome
    Title Phase II: Explore Biomarkers of Response to the Combination
    Description 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
    Time Frame Baseline, Day 1 of Cycle 2 and subsequent cycles, about 9 Months

    Outcome Measure Data

    Analysis Population Description
    This was an outcome measure for the Phase 2 arm. Data were not collected due to the study's termination prior to the opening of Phase 2.
    Arm/Group Title Phase 2 - RPTD GEMOX + Sorafenib
    Arm/Group Description 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. Gemcitabine: Intravenously (IV) on Day 1 of each 14 day cycle, until progression or unacceptable toxicity develops. Oxaliplatin: Intravenously (IV) on Day 2 of each 14 day cycle, until progression or unacceptable toxicity develops. Sorafenib: Orally, twice daily for each 14-day cycle, until progression or unacceptable toxicity develops.
    Measure Participants 0

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Phase 1: GEMOX + Sorafenib Phase 2: RPTD GEMOX + Sorafenib
    Arm/Group Description 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. 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.
    All Cause Mortality
    Phase 1: GEMOX + Sorafenib Phase 2: RPTD GEMOX + Sorafenib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/9 (44.4%) 0/0 (NaN)
    Serious Adverse Events
    Phase 1: GEMOX + Sorafenib Phase 2: RPTD GEMOX + Sorafenib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/9 (33.3%) 0/0 (NaN)
    Cardiac disorders
    Hypotension 1/9 (11.1%) 1 0/0 (NaN) 0
    Gastrointestinal disorders
    Dehydration 2/9 (22.2%) 2 0/0 (NaN) 0
    Diarrhea 1/9 (11.1%) 1 0/0 (NaN) 0
    Vomiting 1/9 (11.1%) 1 0/0 (NaN) 0
    General disorders
    Fever 1/9 (11.1%) 2 0/0 (NaN) 0
    Infections and infestations
    Peritoneal Infection 1/9 (11.1%) 1 0/0 (NaN) 0
    Musculoskeletal and connective tissue disorders
    Muscle Weakness 1/9 (11.1%) 1 0/0 (NaN) 0
    Nervous system disorders
    Dizziness 1/9 (11.1%) 1 0/0 (NaN) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 1/9 (11.1%) 1 0/0 (NaN) 0
    Other (Not Including Serious) Adverse Events
    Phase 1: GEMOX + Sorafenib Phase 2: RPTD GEMOX + Sorafenib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/9 (88.9%) 0/0 (NaN)
    Blood and lymphatic system disorders
    Edema limbs 3/9 (33.3%) 3 0/0 (NaN) 0
    Hemoglobin 8/9 (88.9%) 24 0/0 (NaN) 0
    Leukocytes 6/9 (66.7%) 21 0/0 (NaN) 0
    Lymphopenia 5/9 (55.6%) 11 0/0 (NaN) 0
    Neutrophils 2/9 (22.2%) 8 0/0 (NaN) 0
    Platelets 6/9 (66.7%) 16 0/0 (NaN) 0
    Cardiac disorders
    Supraventricular tachycardia 1/9 (11.1%) 1 0/0 (NaN) 0
    Cardiac ischemia/infarction 1/9 (11.1%) 1 0/0 (NaN) 0
    Hypertension 3/9 (33.3%) 5 0/0 (NaN) 0
    Palpitations 1/9 (11.1%) 1 0/0 (NaN) 0
    Ear and labyrinth disorders
    Hearing (monitoring program) 1/9 (11.1%) 1 0/0 (NaN) 0
    Endocrine disorders
    Hypothyroidism 1/9 (11.1%) 1 0/0 (NaN) 0
    Gastrointestinal disorders
    Vomiting 4/9 (44.4%) 6 0/0 (NaN) 0
    Taste Alteration 2/9 (22.2%) 2 0/0 (NaN) 0
    Diarrhea 3/9 (33.3%) 6 0/0 (NaN) 0
    Abdominal Pain 5/9 (55.6%) 13 0/0 (NaN) 0
    Abdominal Distention 1/9 (11.1%) 2 0/0 (NaN) 0
    Anorexia 6/9 (66.7%) 13 0/0 (NaN) 0
    Ascites 1/9 (11.1%) 1 0/0 (NaN) 0
    Constipation 2/9 (22.2%) 4 0/0 (NaN) 0
    Flatulence 1/9 (11.1%) 2 0/0 (NaN) 0
    Gastritis 1/9 (11.1%) 1 0/0 (NaN) 0
    GI - Other 1/9 (11.1%) 1 0/0 (NaN) 0
    Mucositis oral 1/9 (11.1%) 2 0/0 (NaN) 0
    Nausea 4/9 (44.4%) 9 0/0 (NaN) 0
    General disorders
    Toothache 1/9 (11.1%) 2 0/0 (NaN) 0
    Back Pain 4/9 (44.4%) 6 0/0 (NaN) 0
    Chest Pain 1/9 (11.1%) 2 0/0 (NaN) 0
    Death - Disease Progression 1/9 (11.1%) 1 0/0 (NaN) 0
    Fatigue 7/9 (77.8%) 14 0/0 (NaN) 0
    Fever 2/9 (22.2%) 4 0/0 (NaN) 0
    Headache 1/9 (11.1%) 1 0/0 (NaN) 0
    Joint Pain 2/9 (22.2%) 2 0/0 (NaN) 0
    Pain 1/9 (11.1%) 2 0/0 (NaN) 0
    Pain - Other 3/9 (33.3%) 4 0/0 (NaN) 0
    Pharyngolaryngeal pain 2/9 (22.2%) 3 0/0 (NaN) 0
    Hepatobiliary disorders
    Liver dysfunction 1/9 (11.1%) 1 0/0 (NaN) 0
    Immune system disorders
    Allergic Reaction 2/9 (22.2%) 2 0/0 (NaN) 0
    Metabolism and nutrition disorders
    Alanine aminotransferase increased 5/9 (55.6%) 17 0/0 (NaN) 0
    Alkaline phosphatase increased 6/9 (66.7%) 14 0/0 (NaN) 0
    Aspartate aminotransferase increased 7/9 (77.8%) 18 0/0 (NaN) 0
    Hyperbilirubinemia 2/9 (22.2%) 4 0/0 (NaN) 0
    Hyperglycemia 5/9 (55.6%) 11 0/0 (NaN) 0
    Hyperkalemia 3/9 (33.3%) 3 0/0 (NaN) 0
    Hypermagnesemia 2/9 (22.2%) 5 0/0 (NaN) 0
    Hypernatremia 1/9 (11.1%) 3 0/0 (NaN) 0
    Hypoalbuminemia 7/9 (77.8%) 19 0/0 (NaN) 0
    Hypocalcemia 2/9 (22.2%) 8 0/0 (NaN) 0
    Hypoglycemia 2/9 (22.2%) 3 0/0 (NaN) 0
    Hypokalemia 2/9 (22.2%) 5 0/0 (NaN) 0
    Hypomagnesemia 1/9 (11.1%) 2 0/0 (NaN) 0
    Hyponatremia 3/9 (33.3%) 4 0/0 (NaN) 0
    Hypophosphatemia 4/9 (44.4%) 10 0/0 (NaN) 0
    Musculoskeletal and connective tissue disorders
    Arthritis 1/9 (11.1%) 2 0/0 (NaN) 0
    Nervous system disorders
    Anxiety 1/9 (11.1%) 1 0/0 (NaN) 0
    Depression 1/9 (11.1%) 1 0/0 (NaN) 0
    Peripheral sensory neuropathy 4/9 (44.4%) 14 0/0 (NaN) 0
    Renal and urinary disorders
    Urine Discoloration 1/9 (11.1%) 1 0/0 (NaN) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 2/9 (22.2%) 3 0/0 (NaN) 0
    Ear, nose and throat examination abnormal 1/9 (11.1%) 2 0/0 (NaN) 0
    Skin and subcutaneous tissue disorders
    Rash 2/9 (22.2%) 3 0/0 (NaN) 0
    Pruritus 1/9 (11.1%) 1 0/0 (NaN) 0
    Acne 1/9 (11.1%) 1 0/0 (NaN) 0
    Alopecia 1/9 (11.1%) 1 0/0 (NaN) 0
    Dermatology/Skin - Other 1/9 (11.1%) 1 0/0 (NaN) 0
    Hand-and-foot syndrome 3/9 (33.3%) 3 0/0 (NaN) 0
    Vascular disorders
    Vaginal Hemorrhage 1/9 (11.1%) 2 0/0 (NaN) 0
    Rectal hemorrhage 1/9 (11.1%) 1 0/0 (NaN) 0

    Limitations/Caveats

    Study terminated due to lack of funding prior to the opening of the Phase 2 arm. Minimum required enrollment of 18 evaluable participants for Phase 1 not met.

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Peter J. Hosein MD
    Organization University of Miami
    Phone 3052433462
    Email phosein@miami.edu
    Responsible Party:
    Peter Hosein, Assistant Professor of Clinical, University of Miami
    ClinicalTrials.gov Identifier:
    NCT00955721
    Other Study ID Numbers:
    • 20090256
    • SCCC-2009003
    First Posted:
    Aug 10, 2009
    Last Update Posted:
    Jan 3, 2018
    Last Verified:
    Dec 1, 2017