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

August 9, 2017 updated by: Medical University of South Carolina

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

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

Interventional

Enrollment (Actual)

95

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 116 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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.
Given orally

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.
From the time of randomization until progression, withdrawal due to toxicity or 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.
From day 1 of drug administration until 30 days after the last dose of study drug.
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.
From day 1 drug administration until 30 days after the last dose of study drug.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

May 1, 2016

Study Completion (Actual)

February 1, 2017

Study Registration Dates

First Submitted

April 14, 2009

First Submitted That Met QC Criteria

April 14, 2009

First Posted (Estimate)

April 15, 2009

Study Record Updates

Last Update Posted (Actual)

September 11, 2017

Last Update Submitted That Met QC Criteria

August 9, 2017

Last Verified

October 1, 2015

More Information

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.

Clinical Trials on Liver Cancer

Clinical Trials on bevacizumab

3
Subscribe