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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Medical University of South Carolina
Sponsor:
Information provided by (Responsible Party):
Melanie Thomas, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT00881751
First received: April 14, 2009
Last updated: November 21, 2013
Last verified: November 2013
  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. Erlotinib and sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab, erlotinib, and sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving bevacizumab together with erlotinib is more effective than giving sorafenib in treating patients with liver cancer.

PURPOSE: This randomized phase II trial is studying how well giving bevacizumab together with erlotinib works compared with sorafenib as first-line therapy in treating patients with advanced liver cancer.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Open-Label Multi-Institution Phase II Study of the Combination of Bevacizumab and Erlotinib Compared to Sorafenib in the First-Line Treatment of Patients With Advanced Hepatocellular Carcinoma (HCC)

Resource links provided by NLM:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • Efficacy [ Time Frame: 28 day cycle ] [ Designated as safety issue: No ]
    The primary objective of this study is to estimate clinical efficacy outcomes (based on OS) of patients treated with B+E and patients treated with S. Forty-five patients in each arm who are evaluable for response will be sufficient for this analysis. A patient is evaluable for response if one 28-day cycle of therapy is completed. Enrolled patients who are not evaluable will be replaced, so there will be 45 patients in each arm evaluable for response.


Secondary Outcome Measures:
  • Event-free survival and response rate [ Time Frame: At various points throughout the study duration ] [ Designated as safety issue: No ]
    Secondary outcome measures include event-free survival and response rate as assessed on restaging imaging studies utilizing RECIST 1.1.

  • safety and tolerability [ Time Frame: At various points throught the study duration ] [ Designated as safety issue: Yes ]
    The study will compare (secondary endpoint) the safety and tolerability of B+E vs S. All patients who receive any study drug will be evaluable for toxicity.


Estimated Enrollment: 120
Study Start Date: March 2009
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28.
Biological: bevacizumab
Given IV
Drug: erlotinib hydrochloride
Given orally
Active Comparator: Arm II
Patients receive oral sorafenib tosylate twice daily on days 1-28.
Drug: sorafenib tosylate
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • To estimate the overall survival in patients with advanced hepatocellular carcinoma treated with bevacizumab and erlotinib hydrochloride vs sorafenib tosylate.

Secondary

  • To estimate the event-free survival and tumor response rate of these patients.
  • To evaluate the safety and tolerability of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28.
  • 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.

After completion of study treatment, patients are followed at 30 days and then every 3 months for 1 year.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Pathologically confirmed advanced hepatocellular carcinoma (HCC)

    • Childs-Pugh class A
    • CLIP score ≤ 5
  • Not a candidate for curative surgical resection or loco-regional therapy
  • Measurable disease as per RECIST 1.1 criteria, defined as ≥ 1 previously unirradiated, bidimensionally measurable lesion ≥ 20 mm by CT scan or MRI (triphasic spiral CT scan or MRI employing a "liver protocol" image capture technique required)

    • Bone lesions, ascites, and pleural effusions are not considered measurable lesions
  • No fibrolamellar HCC
  • No known brain metastases
  • No prior organ transplantation

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 75,000/mm³
  • Hemoglobin ≥ 9 g/dL
  • Transaminases ≤ 5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 2.0 times ULN
  • PT ≤ 1.8 times ULN

    • Prolonged INR allowed for patients who require full dose anticoagulation
  • Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 45 mL/min
  • Urine protein < 2+ by urine dipstick OR urine protein ≤ 1 g by 24-hour urine collection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 weeks after completion of study treatment
  • Able to take and absorb oral medication
  • No active infection requiring parenteral therapy
  • No known HIV or AIDS
  • No uncontrolled blood pressure (BP), defined as systolic BP ≥ 150 mm Hg and/or diastolic BP ≥ 100 mm Hg
  • No uncontrolled or significant cardiovascular disease, including any of the following:

    • Myocardial infarction within the past 6 months
    • Uncontrolled angina within the past 6 months
    • New York Heart Association class II-IV congestive heart failure
    • Grade 3 cardiac valve dysfunction
    • Cardiac arrhythmia not controlled by medication
    • Stroke or transient ischemic attack within the past 6 months
    • Arterial thrombotic event of any type within the past 6 months
  • No significant or symptomatic vascular disease (e.g., aortic aneurysm, aortic dissection, or peripheral vascular disease) within the past 6 months
  • No decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy not corrected by conservative measures
  • No grade 3 bleeding esophageal or gastric varices within the past 2 months

    • Prior variceal bleeding allowed provided patient has undergone banding or sclerotherapy and there has been no evidence of bleeding for 2 months
  • No gastric varices ≥ grade 2
  • No hemoptysis (i.e., ≥ ½ teaspoon of bright red blood per episode) within the past month
  • No evidence of bleeding diathesis or coagulopathy
  • No concurrent uncontrolled illness, including, but not limited to, a history of or current evidence of unexplained nephrotic syndrome or other severe illness/disease that would preclude study participation
  • No history of hypertensive crisis or hypertensive encephalopathy
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No serious, non-healing wound, active ulcer, or untreated bone fracture
  • No significant traumatic injury within the past 28 days
  • No history of allergy to bevacizumab, erlotinib hydrochloride, sorafenib tosylate, or related compounds
  • No other primary malignancy within the past 5 years, except carcinoma in situ of the cervix or urinary bladder or nonmelanoma skin cancer
  • No mental incapacitation or psychiatric illness that would preclude study participation
  • Not incarcerated or compulsorily detained (i.e., involuntarily incarcerated) for treatment of either a psychiatric or physical illness (e.g., infectious disease)

PRIOR CONCURRENT THERAPY:

  • Prior surgery, local ablation, trans-arterial hepatic artery embolization, or trans-arterial chemoembolization are allowed provided the lesion(s) have progressed since treatment OR there are additional measurable, untreated lesions present
  • No prior systemic therapy for HCC
  • No prior organ transplantation
  • More than 7 days since prior minor surgical procedures, fine needle aspirations, or core biopsies (excluding placement of a vascular access device)
  • More than 28 days since any prior therapy
  • More than 28 days since prior and no concurrent major surgical procedure or open biopsy
  • More than 28 days since prior and no concurrent participation in another experimental drug study
  • No other concurrent anticancer or antitumor therapy, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy
  • No other concurrent investigational agents
  • No concurrent warfarin (other types of anticoagulation allowed)
  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: NCT00881751

Contacts
Contact: Andie Adelman 843-792-1507 adelman@musc.edu

Locations
United States, California
USC/Norris Comprehensive Cancer Center and Hospital Recruiting
Los Angeles, California, United States, 90033-0804
Contact: Anthony B. El-Khoueiry, MD    323-865-3967    elkhouei@usc.edu   
California Pacific Medical Center Recruiting
San Francisco, California, United States, 94115
Contact: Ari Baron, MD    415-923-4840      
Contact: Brenda Eng    415-600-1775      
United States, New York
Columbia University/ New York Presbyterian Hospital Recruiting
New York, New York, United States, 10032
Contact: Abby Siegel, MD    212-305-9781      
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Andie R Adelman    843-792-1507      
Contact: Melanie B Thomas, M.D.    843-792-5085      
Principal Investigator: Melanie Thomas, MD         
United States, Tennessee
Tennessee Oncology, PLLC at Sarah Cannon Cancer Center Recruiting
Nashville, Tennessee, United States, 37203
Contact: Johanna Bendell, MD    615-329-7274      
United States, Virginia
UVA Cancer Center Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Geoff R Weiss, MD    434-246-0066      
Contact: Christina Taylor, RN    434-243-0425      
Sponsors and Collaborators
Medical University of South Carolina
Investigators
Principal Investigator: Melanie B. Thomas, MD Medical University of South Carolina
  More Information

Additional Information:
No publications provided

Responsible Party: Melanie Thomas, Associate Professor, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT00881751     History of Changes
Other Study ID Numbers: 101282, MUSC-101282, GENENTECH-AVF4481s
Study First Received: April 14, 2009
Last Updated: November 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Medical University of South Carolina:
adult primary hepatocellular carcinoma
advanced adult primary liver cancer
recurrent adult primary liver cancer

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma, Hepatocellular
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Bevacizumab
Sorafenib
Erlotinib
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

ClinicalTrials.gov processed this record on July 22, 2014