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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatocellular Carcinoma (HCC)

Intervention / Treatment
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* Drug: brivanib (active)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>no comparator to brivanib | Drug: brivanib (active)<br>* Tablet, Oral, Brivanib 800 mg, once daily, until progression<br>* Other names: BMS-582664;|

What is the study measuring?
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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 | 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) | 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) | 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) | 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 | 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 | 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) | 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) | 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) | 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 | 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) |