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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00881751
First Posted: April 15, 2009
Last Update Posted: September 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Medical University of South Carolina
  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: None (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:
  • Overall Survival [ Time Frame: from date of day 1 until the date of death ]
    Overall survival is defined as the time from treatment day 1 until death from any cause. Patients still alive at the end of follow up,patients who withdrew consent from the trial and patients who were lost to follow up will have their survival time censored at the last date of contact.


Secondary Outcome Measures:
  • Event-free Survival [ Time Frame: From the time of randomization until progression, withdrawal due to toxicity or any other clinical event requiring withdrawal from the study. ]
    EFS is defined as the time from randomization to any of the following three types of events: 1 - progression; 2 - withdrawal due to excessive toxicity; 3 - any other clinical event requiring withdrawal from the study.

  • Number of SAEs Experienced [ Time Frame: From day 1 of drug administration until 30 days after the last dose of study drug. ]
    The study will report the number of SAEs experienced in each arm. All patients who receive any study drug will be evaluable for toxicity.

  • Response Rate [ Time Frame: From day 1 drug administration until 30 days after the last dose of study drug. ]
    Secondary outcome measures include response rate as assessed on restaging imaging studies utilizing RECIST 1.1.


Enrollment: 95
Study Start Date: March 2009
Study Completion Date: February 2017
Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: bevacizumab and erlotinib
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 2: sorafenib tosylate
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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 116 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00881751


Locations
United States, California
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90033-0804
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, New York
Columbia University/ New York Presbyterian Hospital
New York, New York, United States, 10032
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Tennessee Oncology, PLLCat Sarah Cannon Cancer Center
Nashville, Tennessee, United States, 37203
United States, Virginia
UVA Cancer Center
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
Medical University of South Carolina
  More Information

Responsible Party: Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT00881751     History of Changes
Other Study ID Numbers: 101282
MUSC-101282
GENENTECH-AVF4481s
First Submitted: April 14, 2009
First Posted: April 15, 2009
Results First Submitted: June 13, 2017
Results First Posted: September 11, 2017
Last Update Posted: September 11, 2017
Last Verified: October 2015

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:
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
Erlotinib Hydrochloride
Niacinamide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients


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