A Phase II Open Label Study of BMS-582664 in Locally Advanced or Metastatic Hepatocellular Cancer

November 10, 2023 updated by: Bristol-Myers Squibb

A Phase II Open Label Study of Brivanib (BMS582664), Administered Orally At A Dose of 800 mg Daily In Subjects With Unresectable, Locally Advanced or Metastatic Hepatocellular Carcinoma Who Have Received Either No Prior Systemic Therapy or One Prior Regimen of Angiogenesis Inhibitor Therapy

The purpose of this clinical research study is to learn if BMS-582664 can shrink or slow the growth of advanced liver cancer. The safety of this treatment will also be studied.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

137

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

  • France
      • Marseille, France, 13273
        • Local Institution
      • Reims Cedex, France, 51092
        • Local Institution
      • Rennes, France, 35042
        • Local Institution
      • Villejuif, France, 94805
        • Local Institution
  • Hong Kong
      • Shatin, Nt.,, Hong Kong
        • Local Institution
  • Korea, Republic of
      • Gyeonggi-Do, Korea, Republic of, 410-769
        • Local Institution
      • Seoul, Korea, Republic of, 135-710
        • Local Institution
      • Seoul, Korea, Republic of, 138-736
        • Local Institution
      • Seoul, Korea, Republic of, 152-703
        • Local Institution
  • Malaysia
      • Kuala Lumpur, Malaysia, 56000
        • Local Institution
    • Negeri Sembilan
      • Nilai, Negeri Sembilan, Malaysia, 71800
        • Local Institution
  • Philippines
      • Cebu City, Philippines, 6000
        • Local Institution
      • Davao City, Philippines, 8000
        • Local Institution
      • Quezon, Philippines, 1102
        • Local Institution
  • Singapore
      • Singapore, Singapore, 308433
        • Local Institution
      • Singapore, Singapore, 169610
        • Local Institution
  • Taiwan
      • Tainan, Taiwan, 704
        • Local Institution
      • Taipei, Taiwan, 112
        • Local Institution
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
      • Duarte, California, United States, 91010-3000
        • City of Hope National Medical Center
      • Los Angeles, California, United States, 90095
        • Harbor-UCLA Medical Center
      • Los Angeles, California, United States, 90095-1678
        • Harbor UCLA Medical Center
    • Delaware
      • Newark, Delaware, United States, 19713
        • Christiana Care Health Services
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Miller School of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Chicago, Illinois, United States, 60611
        • Northwestern University Feinberg School of Medicine
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Wayne State University
    • Missouri
      • Saint Louis, Missouri, United States, 63104
        • Saint Louis University
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • The Cancer Center at Hackensack University Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Milton S. Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19141
        • Albert Einstein Cancer Center
    • Texas
      • Dallas, Texas, United States, 75390
        • Univ Of Texas Southwestern
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
      • Houston, Texas, United States, 77030-4009
        • MD Anderson Cancer Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of hepatocellular carcinoma (HCC) ≥ 2cm based on:
  • Biopsy OR
  • Radiological evidence of HCC by contrast-enhanced CT scan or contrast-enhanced AND
  • Blood test positive for Hepatitis B or C AND
  • Alpha fetoprotein above > 400 mg/L
  • Not appropriate for curative surgery
  • Screening Blood Pressure <150/100 mmHg, Left Ventricular Ejection Fraction (LVEF) >50%

Exclusion Criteria:

  • Heart Attack within 12 months, uncontrolled chest pain within 6 months
  • Ascites resistant to diuretic medication therapy
  • Portal-systemic encephalopathy
  • Portal hypertension with bleeding esophageal or gastric varices within the past 2 months
  • Deficiency of sodium in the blood with sodium < 125 mEq/L
  • Subjects with serious non-healing wounds, ulcers or bone fractures

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
no comparator to brivanib
Drug: brivanib (active)
Tablet, Oral, Brivanib 800 mg, once daily, until progression
Other Names:
  • BMS-582664

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS) Rate at 6 Months Per Independent Response Review Committee (IRRC) in Cohort A
Time Frame: From first dose up to approximately 6 months after first dose

The percent of participants who have not progressed or died prior to 6 months from the date of their first dose. Participants who have neither progressed nor died but had their last tumor assessment prior to 6 months will not be categorized as progression free and will not be included. Tumor response was measured by the IRRC using mWHO criteria.

Progression is defined as a 25% or more increase in the sum of all index lesion areas taking as reference the smallest sum recorded at or following baseline.
From first dose up to approximately 6 months after first dose
The Number of Participants Experiencing Adverse Events (AEs)
Time Frame: From first dose up to 30 days post last dose (up to approximately 34 months)
An Adverse Event (AE) is defined as any new untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment.
From first dose up to 30 days post last dose (up to approximately 34 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor Response Rate Per Independent Response Review Committee (IRRC)
Time Frame: From first dose to the date of the first documented response (up to approximately 34 months)

The percent of participants whose best overall response is a partial response (PR) or complete response (CR). Tumor measurements by CT/ MRI of the chest, abdomen and pelvis will be obtained at pre-treatment (within 28 days prior to the start of treatment) and every 6 weeks.

Complete Response (CR): Disappearance of all known disease. Must be confirmed 4 or more weeks later.

Partial Response (PR): A 50% or more decrease in the sum of all index lesion areas compared to the baseline sum and no unequivocal progression of existing non-index lesions. In addition, there can be no appearance of new lesions. Must be confirmed 4 or more weeks later.
From first dose to the date of the first documented response (up to approximately 34 months)
Disease Control Rate Per Independent Response Review Committee (IRRC)
Time Frame: From first dose to the date of the first documented response (up to approximately 34 months)

The percent of participants whose best response is a partial response (PR), complete response (CR) or stable disease (SD).

Complete Response (CR): Disappearance of all known disease. Must be confirmed 4 or more weeks later.

Partial Response (PR): A 50% or more decrease in the sum of all index lesion areas compared to the baseline sum and no unequivocal progression of existing non-index lesions. In addition, there can be no appearance of new lesions. Must be confirmed 4 or more weeks later.

Stable Disease (SD): A decrease of 50% or more or an increase of 25% or more in the sum of all index lesion areas compared to baseline cannot be established. There can be no appearance of new lesions. Documentation must occur 6 weeks (42 days) or more from the baseline determination.
From first dose to the date of the first documented response (up to approximately 34 months)
Overall Survival for Participants With No Prior Systemic Therapy
Time Frame: From first dose to the date of death (up to approximately 34 months)
The time (in months) from first dosing until the date of death. For those participants who have not died, survival duration will be censored at the last date the participant was known to be alive.
From first dose to the date of death (up to approximately 34 months)
Overall Survival for Participants With One Prior Angiogenesis Inhibitor Therapy
Time Frame: From first dose to the date of death (up to approximately 34 months)
The time (in months) from first dosing until the date of death. For those participants who have not died, survival duration will be censored at the last date the participant was known to be alive.
From first dose to the date of death (up to approximately 34 months)
Progression Free Survival (PFS) Per Independent Response Review Committee (IRRC)
Time Frame: From first dose to the date of the first documented progression (up to approximately 34 months)

The time (in months) from first dosing date to the date of progression per IRRC. Participants who die without a reported prior progression will be considered to have progressed on their date of death (as found in the BMS clinical database). Participants who did not progress or die will be censored on the date of their last tumor assessment. Participants who have only baseline tumor assessment will be censored on the first dosing date.

Progression is defined as a 25% or more increase in the sum of all index lesion areas taking as reference the smallest sum recorded at or following baseline.
From first dose to the date of the first documented progression (up to approximately 34 months)
Time to Response Per Independent Response Review Committee (IRRC)
Time Frame: From first dose to the date of the first documented response (up to approximately 34 months)

The time from the first dose of study therapy until measurement criteria are first met for Partial response (PR) or complete response (CR), whichever is recorded first.

Complete Response (CR): Disappearance of all known disease. Must be confirmed 4 or more weeks later.

Partial Response (PR): A 50% or more decrease in the sum of all index lesion areas compared to the baseline sum and no unequivocal progression of existing non-index lesions. In addition, there can be no appearance of new lesions. Must be confirmed 4 or more weeks later.
From first dose to the date of the first documented response (up to approximately 34 months)
Duration of Response Per Independent Response Review Committee (IRRC)
Time Frame: From first dose to the date of documented progressive disease or death (up to approximately 34 months)

Duration of response will be computed as from time measurement criteria are met for PR or CR until the date of documented progressive disease or death. Participants who neither relapse nor die will be censored on the date of their last tumor assessment. Progression is defined as a 25% or more increase in the sum of all index lesion areas taking as reference the smallest sum recorded at or following baseline.

Complete Response (CR): Disappearance of all known disease. Must be confirmed 4 or more weeks later.

Partial Response (PR): A 50% or more decrease in the sum of all index lesion areas compared to the baseline sum and no unequivocal progression of existing non-index lesions. In addition, there can be no appearance of new lesions. Must be confirmed 4 or more weeks later.
From first dose to the date of documented progressive disease or death (up to approximately 34 months)
Change From Baseline to End of Treatment in FHSI-8 Total Score
Time Frame: Baseline and end of treatment (up to approximately 33 months)
FHSI-8 (Functional Assessment of Cancer Therapy, Hepatobiliary, Symptom Index) was used to assess HCC-related symptoms. The FHSI-8 includes eight items representing HCC-related symptoms; each symptom is rated by participants on a scale of from 0 to 4. The FHSI-8 total score ranges in value from 0 to 32, with higher scores representing fewer symptoms and lower scores representing more symptoms.
Baseline and end of treatment (up to approximately 33 months)

Collaborators and Investigators

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

Sponsor

Bristol-Myers Squibb

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

December 31, 2006

Primary Completion (Actual)

April 30, 2010

Study Completion (Actual)

April 30, 2010

Study Registration Dates

First Submitted

July 20, 2006

First Submitted That Met QC Criteria

July 20, 2006

First Posted (Estimated)

July 21, 2006

Study Record Updates

Last Update Posted (Actual)

December 1, 2023

Last Update Submitted That Met QC Criteria

November 10, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA182-006

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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