- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00881751
Bevacizumab and Erlotinib or Sorafenib as First-Line Therapy in Treating Patients With Advanced Liver Cancer
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)
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
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Los Angeles, California, United States, 90033-0804
- USC/Norris Comprehensive Cancer Center and Hospital
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San Francisco, California, United States, 94115
- California Pacific Medical Center
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-
New York
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New York, New York, United States, 10032
- Columbia University/ New York Presbyterian Hospital
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South Carolina
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Charleston, South Carolina, United States, 29425
- Hollings Cancer Center at Medical University of South Carolina
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Tennessee
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Nashville, Tennessee, United States, 37203
- Tennessee Oncology, PLLCat Sarah Cannon Cancer Center
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Virginia
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Charlottesville, Virginia, United States, 22908
- UVA Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Given IV
Given orally
|
Active Comparator: Arm 2: sorafenib tosylate
Patients receive oral sorafenib tosylate twice daily on days 1-28.
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Given orally
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
from date of day 1 until the date of death
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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From the time of randomization until progression, withdrawal due to toxicity or any other clinical event requiring withdrawal from the study.
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Number of SAEs Experienced
Time Frame: From day 1 of drug administration until 30 days after the last dose of study drug.
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The study will report the number of SAEs experienced in each arm.
All patients who receive any study drug will be evaluable for toxicity.
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From day 1 of drug administration until 30 days after the last dose of study drug.
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Response Rate
Time Frame: From day 1 drug administration until 30 days after the last dose of study drug.
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Secondary outcome measures include response rate as assessed on restaging imaging studies utilizing RECIST 1.1.
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From day 1 drug administration until 30 days after the last dose of study drug.
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Digestive System Neoplasms
- Liver Diseases
- Liver Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Protein Kinase Inhibitors
- Erlotinib Hydrochloride
- Sorafenib
- Bevacizumab
Other Study ID Numbers
- 101282
- MUSC-101282
- GENENTECH-AVF4481s
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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