Bevacizumab and Sorafenib as First-Line Therapy in Treating Patients With Locally Advanced or Metastatic Liver Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00867321
First received: March 20, 2009
Last updated: June 17, 2012
Last verified: October 2011
  Purpose

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and sorafenib may also stop the growth of liver cancer by blocking blood flow to the tumor.

PURPOSE: This randomized phase I/II trial is studying the best dose of bevacizumab when given together with sorafenib as first-line therapy in treating patients with locally advanced or metastatic liver cancer.(Phase I closed to accrual as of 11/03/2010)


Condition Intervention Phase
Liver Cancer
Biological: bevacizumab
Drug: sorafenib tosylate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Phase I/II Randomized Trial of Sorafenib and Bevacizumab as First-Line Therapy in Patients With Locally Advanced or Metastatic Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose [ Designated as safety issue: No ]
  • Time to progression [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Tumor response at 6 months [ Designated as safety issue: No ]
  • Time to progression [ Designated as safety issue: No ]
  • Cellular biomarkers from blood samples (i.e., VEGFA, VEGFC, HGF, Ang-2, PlGF, soluble VEGFR1, soluble VEGFR2, soluble KIT, bFGF SDF1-α, CEC, and CEPC) at baseline and relative change from baseline [ Designated as safety issue: No ]
  • Utility of biomarkers to predict response to this combination treatment [ Designated as safety issue: No ]

Estimated Enrollment: 97
Study Start Date: April 2009
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (Phase II)
Patients receive oral sorafenib tosylate on days 1-28 twice daily and bevacizumab IV on days 1 and 15.
Biological: bevacizumab
Given IV
Drug: sorafenib tosylate
Given orally
Experimental: Arm II (Phase II)
Patients receive oral sorafenib tosylate twice daily on days 1-28.
Drug: sorafenib tosylate
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of bevacizumab in combination with sorafenib tosylate in patients with locally advanced or metastatic hepatocellular carcinoma. (Phase I closed to accrual as of 11/03/2010)
  • Determine time to progression in these patients. (Phase II)

Secondary

  • Determine the safety of this regimen in these patients. (Phase I closed to accrual as of 11/03/2010)
  • Assess tolerability of this regimen in these patients. (Phase I closed to accrual as of 11/03/2010)
  • Determine overall survival of these patients. (Phase II)
  • Determine tumor response (at 6 months) in patients treated with this regimen. (Phase II)
  • Determine progression-free survival of these patients. (Phase II)
  • Determine response rate in patients treated with this regimen. (Phase II)
  • Assess the occurrence of adverse events in these patients. (Phase II)

Tertiary

  • Determine the relationship between tumor biomarkers and circulating biomarkers of vascular response and clinical outcome in patients treated with this regimen.

OUTLINE: This is a phase I, dose escalation study followed by a randomized phase II study.

  • Phase I (closed to accrual as of 11/03/2010): Patients receive oral sorafenib tosylate twice daily on days 1-28 and bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Phase II: Patients are stratified according to gender (female vs male), ECOG performance status (0 vs 1), and Child-Pugh class (A vs B7). Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive oral sorafenib tosylate on days 1-28 twice daily and bevacizumab IV on days 1 and 15.
    • Arm II: Patients receive oral sorafenib tosylate twice daily on days 1-28. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for analysis of circulating endothelial cells and circulating endothelial progenitor cells and angiogenic proteins in plasma by ELISA.

After completion of study treatment, patients are followed for 3 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed hepatocellular carcinoma

    • Locally advanced or metastatic disease that is not amenable to treatment with surgery or to orthotopic liver transplant
    • Child Pugh class A or B7 disease
  • Measurable disease
  • No mixed cholangiocarcinoma/hepatocellular carcinoma
  • No current or previously resected brain metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy ≥ 3 months
  • ANC ≥ 1,200/mm³
  • Platelet count ≥ 75,000/mm³
  • Hemoglobin ≥ 9.0 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST ≤ 5 times ULN
  • Alkaline phosphatase ≤ 5 times ULN
  • Urine protein ≤ 1+ by urine protein:creatinine ratio OR 24-hour urine protein < 1 g
  • QTc interval ≤ 500 msec on baseline EKG
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 2 weeks after sorafenib tosylate and 6 months after bevacizumab
  • None of the following risk factors for decreased LVEF:

    • Prior treatment with anthracyclines
    • History of myocardial infarction within the past 12 months
  • No uncontrolled hypertension (defined as systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 100 mm Hg) despite optimal medical management
  • No New York Heart Association class III-IV congestive heart failure
  • No cardiac ventricular arrhythmias requiring antiarrhythmic therapy
  • No history of hypertensive crisis or hypertensive encephalopathy
  • No cardiac ventricular arrhythmia requiring anti-arrhythmic therapy within the past 6 months
  • None of the following within the past 6 months:

    • Transient ischemic attack
    • Cerebrovascular accident
    • Unstable angina or angina
    • Clinically significant peripheral artery disease (i.e., claudication in less than one block) or any other arterial thrombotic event
    • Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
    • Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis
  • No active or recent history of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within the past 30 days
  • No evidence of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation)
  • No significant traumatic injury within the past 4 weeks
  • No serious or non-healing wound, ulcer, or bone fracture
  • No uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
  • No other active malignancy within the past 3 years, except nonmelanotic skin cancer or carcinoma in situ of the cervix
  • No comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or sorafenib tosylate

PRIOR CONCURRENT THERAPY:

  • No prior systemic chemotherapy regimens for hepatocellular carcinoma
  • No prior external beam radiation to the primary site
  • No prior central thoracic radiation therapy (RT), including RT to the heart
  • No prior radiation (if given for another malignancy) to ≥ 25% of the bone marrow
  • At least 6 weeks since prior chemoembolization, radioembolization, radiofrequency ablation, or other local ablative therapies
  • More than 4 weeks since prior biologic, hormonal, or immune therapy
  • More than 4 weeks since prior and no concurrent major surgical procedure or open biopsy
  • More than 7 days since prior core biopsy or other minor surgical procedure (placement of a vascular access device allowed)
  • No concurrent investigational agent which would be considered as a treatment for the primary neoplasm
  • No concurrent anticoagulants, except low-dose warfarin or heparin for deep venous thrombosis prophylaxis
  • No other concurrent treatment for prior malignancy (other than hormonal therapy)
  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: NCT00867321

  Show 177 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Steven R. Alberts, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00867321     History of Changes
Other Study ID Numbers: CDR0000637866, NCCTG-N0745
Study First Received: March 20, 2009
Last Updated: June 17, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adult primary hepatocellular carcinoma
advanced adult primary liver cancer
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Bevacizumab
Sorafenib
Niacinamide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on September 18, 2014