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

Hepatocellular Carcinoma (HCC) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00355238
• Other study ID #: CA182-006
• Status: Completed
• Phase: Phase 2
• Start date: December 31, 2006
• Est. completion date: April 30, 2010

Study information

• Verified date: November 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 137
• Est. completion date: April 30, 2010
• Est. primary completion date: April 30, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma (HCC)

Intervention

Drug:
• brivanib (active)
Tablet, Oral, Brivanib 800 mg, once daily, until progression

Locations

Country	Name	City	State
France	Local Institution	Marseille
France	Local Institution	Reims Cedex
France	Local Institution	Rennes
France	Local Institution	Villejuif
Hong Kong	Local Institution	Shatin, Nt.,
Korea, Republic of	Local Institution	Gyeonggi-Do
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Malaysia	Local Institution	Kuala Lumpur
Malaysia	Local Institution	Nilai	Negeri Sembilan
Philippines	Local Institution	Cebu City
Philippines	Local Institution	Davao City
Philippines	Local Institution	Quezon
Singapore	Local Institution	Singapore
Singapore	Local Institution	Singapore
Taiwan	Local Institution	Tainan
Taiwan	Local Institution	Taipei
United States	Northwestern University Feinberg School Of Medicine	Chicago	Illinois
United States	University Of Chicago	Chicago	Illinois
United States	Univ Of Texas Southwestern	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	City Of Hope National Medical Center	Duarte	California
United States	City Of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	The Cancer Center At Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	MD Anderson Cancer Center	Houston	Texas
United States	Md Anderson Cancer Center	Houston	Texas
United States	University Of Iowa Hospitals And Clinics	Iowa City	Iowa
United States	Harbor UCLA Medical Center	Los Angeles	California
United States	Harbor-Ucla Medical Center	Los Angeles	California
United States	University Of Miami Miller School Of Medicine	Miami	Florida
United States	Medical College Of Wisconsin	Milwaukee	Wisconsin
United States	Christiana Care Health Services	Newark	Delaware
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Saint Louis University	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  France,  Hong Kong,  Korea, Republic of,  Malaysia,  Philippines,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) Rate at 6 Months Per Independent Response Review Committee (IRRC) in Cohort A	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
Primary	The Number of Participants Experiencing Adverse Events (AEs)	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	Tumor Response Rate Per Independent Response Review Committee (IRRC)	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)
Secondary	Disease Control Rate Per Independent Response Review Committee (IRRC)	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)
Secondary	Overall Survival for Participants With No Prior Systemic Therapy	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)
Secondary	Overall Survival for Participants With One Prior Angiogenesis Inhibitor Therapy	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)
Secondary	Progression Free Survival (PFS) Per Independent Response Review Committee (IRRC)	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)
Secondary	Time to Response Per Independent Response Review Committee (IRRC)	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)
Secondary	Duration of Response Per Independent Response Review Committee (IRRC)	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)
Secondary	Change From Baseline to End of Treatment in FHSI-8 Total Score	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)