Gemcitabine, Oxaliplatin in Combination With Bevacizumab in Patients With Hepatocellular Carcinoma

This study has been completed.
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Genentech, Inc.
Sanofi-Synthelabo
Eli Lilly and Company
Information provided by (Responsible Party):
Andrew X. Zhu, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00142467
First received: August 31, 2005
Last updated: March 15, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to test the safety of bevacizumab when given in combination with gemcitabine and oxaliplatin and to see what effects (good or bad) it has on patients with hepatocellular carcinoma.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: Gemcitabine
Drug: Oxaliplatin
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Gemcitabine, Oxaliplatin in Combination With Bevacizumab (Avastin) in Patients With Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Time to disease progression of gemcitabine, oxaliplatin and bevacizumab regimen in patients with hepatocellular carcinoma. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years


Secondary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Objective response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    From date of randomization until the date of death from any cause, assessed up to 2 years


Enrollment: 33
Study Start Date: April 2004
Study Completion Date: June 2011
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab, Gemcitabine, Oxaliplatin
For cycle 1 (14 days), bevacizumab 10 mg/kg was administered alone on day 1. For cycle 2 and beyond (28 days/cycle), bevacizumab 10 mg/kg was administered on days 1 and 15, gemcitabine 1,000 mg/m2 was administered as a dose rate infusion at 10 mg/m2/min followed by oxaliplatin at 85 mg/m2 on days 2 and 16. All drugs were administered intravenously until progression, intolerance, patient withdrawal, or death.
Drug: Gemcitabine
Other Name: Gemzar
Drug: Oxaliplatin
Other Name: Eloxatin
Drug: Bevacizumab
Other Name: Avastin

Detailed Description:
  • Treatment is given in cycles, each cycle (except for cycle 1) is 4 weeks long. Cycle 1 is only 2 weeks long.
  • During cycle one only, bevacizumab will be given intravenously on day one. Two weeks after receiving bevacizumab, the patient will return to the clinic for treatment with all 3 study drugs.
  • During cycle 2 and every cycle thereafter patients will receive; bevacizumab intravenously on day one and day 15; gemcitabine intravenously on day 2 and day 16; oxaliplatin intravenously on day 2 and day 16.
  • The following evaluations will be conducted on day 1 and day 15 of each cycle (once every 2 weeks): physical examination, vital signs, medical history, blood tests and urine tests.
  • Tumor measurements done by CT and/or MRI will be repeated at the end of cycle 3 and every 2 cycles thereafter.
  • Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) of the liver and Perfusions CT scans will also be done on days 10-12 following bevacizumab treatment during cycle 1, and the Perfusion CT will be repeated at the end of cycle 3.
  • Once study treatment is stopped the following evaluations will be performed: physical exam, vital signs, blood work, urine tests, CT scan of chest, abdomen and pelvis, and tumor measurements by CT or MRI scans.
  • Follow-up will consist of physical examinations and blood tests every 6 months.
  • Patients will continue to receive study treatment as long as there is no disease progression or unacceptable side affects.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Unresectable or metastatic hepatocellular carcinoma
  • Measurable tumors
  • Adequate hepatic function: total bilirubin < 3.0mg/dl; AST < 7x ULN
  • Adequate bone marrow function: ANC > 1,000/mm3; platelets > 75,000/mm3
  • INR < 1.5 for those who are not on anticoagulation
  • Up to two prior chemotherapy regimens for hepatocellular carcinoma
  • 18 years of age or older
  • ECOG performance status of 0-1
  • Life expectancy of > 12 weeks

Exclusion Criteria:

  • Clinically apparent central nervous system metastases or carcinomatous meningitis
  • Uncontrolled serious medical or psychiatric illness
  • Pregnant or lactating women
  • Current or recent (within 4 weeks of first study infusion) participation in experimental study drug
  • Uncontrolled hypertension
  • Significant proteinuria
  • Serious, non-healing wound, ulcer, or bone fracture
  • Evidence of bleeding diathesis or coagulopathy
  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: NCT00142467

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Genentech, Inc.
Sanofi-Synthelabo
Eli Lilly and Company
Investigators
Principal Investigator: Andrew Zhu, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Andrew X. Zhu, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00142467     History of Changes
Other Study ID Numbers: 03-390
Study First Received: August 31, 2005
Last Updated: March 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Unresectable hepatocellular carcinoma
Metastatic hepatocellular carcinoma
gemcitabine
oxaliplatin
bevacizumab
Avastin

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Bevacizumab
Gemcitabine
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on October 20, 2014