Brivanib Metastatic Renal Cell Carcinoma

Brivanib (BMS-582664, Brivanib Alaninate) in Treatment of Refractory Metastatic Renal Cell Carcinoma - A Phase II Pharmacodynamic and Baseline Biomarker Study

Sponsors

Lead Sponsor: Abramson Cancer Center of the University of Pennsylvania

Source Abramson Cancer Center of the University of Pennsylvania
Brief Summary

This is a phase II study of an investigational agent, brivanib, in patients with refractory metastatic renal cell carcinoma. This study will evaluate the safety and effectiveness of brivanib in renal cell carcinoma, and explore the activity of this drug in this population to determine whether imaging and molecular features of the tumors can be used to predict response. Approximately 30 people with advanced kidney cancer will be enrolled on this study at the University of Pennsylvania.

Detailed Description

The primary objective of this clinical trial is to determine the efficacy of brivanib in the treatment of metastatic renal cell carcinoma in terms of progression-free survival (PFS) in patients who have progressed on treatment with sunitinib, sorafenib, bevacizumab, or pazopanib. The primary endpoint of the trial will be PFS at 16 weeks. The secondary objectives are to further examine the safety and tolerability profile of brivanib, to examine the efficacy of brivanib in this population in terms of best overall response, response rate, progression-free survival, and overall survival, to describe baseline and changes in I-cG250 PET/CT in relation to observed therapeutic effects, to describe novel baseline histologic features of these tumors in relation to observed therapeutic effects. Modalities will include Von Hippel-Lindau gene (VHL) and hypoxia-inducible factor 1 gene (HIF-1) expression assessment and a novel histo-cytometric assessment of the tumor microenvironment in terms of p-STAT3, p-ERK, Ki67, VEGFR2, FGFR1 expression, to describe changes in circulating collagen IV on brivanib in relation to therapeutic effects, to explore the relationship between single nucleotide polymorphisms in angiogenesis-related genes and the activity of brivanib in the treatment of these patients.

Overall Status Terminated
Start Date 2011-11-01
Completion Date 2013-09-01
Primary Completion Date 2013-09-01
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Progression Free Survival (PFS) 16 weeks
Secondary Outcome
Measure Time Frame
Best Overall Response Rated for Each Patients as Assessed by RECIST 1.1 Guidelines Every 8 weeks
Overall Survival Every 8 weeks
Change in Total Antibody Binding as Assessed by 124I-cG250 PET/CT Imaging (Correlative Studies) At baseline and 8 weeks
Response Rate for All Patients Every 8 weeks
Molecular Markers At baseline
Changes in Collagen IV Levels At baseline and week 3
Germline Polymorphisms and Assessment of Relationship to Toxicity and Clinical Outcome At baseline and week 3
Blood Pressure Data At baseline, day 1 weeks 3,6,8,12,16 and every 6-8 weeks thereafter
Toxicity as Assessed by NCI CTCAE Version 4.0 Day 1, weeks 3,6,9,12,16, and every 6-8 weeks thereafter
Enrollment 10
Condition
Intervention

Intervention Type: Drug

Intervention Name: Brivanib alaninate

Description: Brivanib by mouth daily at a dose of 800mg.

Arm Group Label: Arm 1

Intervention Type: Genetic

Intervention Name: Polymerase chain reaction

Description: Undergo 1241-cG250 PET/CT imaging (correlative studies)

Arm Group Label: Arm 1

Other Name: PCR

Intervention Type: Other

Intervention Name: Iodine I 124 chimeric monoclonal antibody G250

Description: Undergo 124I-cG250 PET/CT imaging (correlative studies)

Arm Group Label: Arm 1

Intervention Type: Procedure

Intervention Name: Positron emission tomography/computed tomography

Description: Undergo 1241-cG250 PET/CT imaging (correlative studies)

Arm Group Label: Arm 1

Intervention Type: Genetic

Intervention Name: Protein expression analysis

Description: Correlative studies

Arm Group Label: Arm 1

Intervention Type: Other

Intervention Name: Immunohistochemistry

Description: correlative studies

Arm Group Label: Arm 1

Other Name: immunohistochemistry staining method

Eligibility

Criteria:

Inclusion Criteria: - Male and female adults with metastatic renal cell carcinoma - Patients will have tumors that bear a clear cell component that comprises greater than or equal to 50% of the tumor. - Disease must be measurable in accord with RECIST 1.1 guidelines. - Patients who have developed progressive disease or intolerance on treatment with sorafenib, sunitinib, bevacizumab, or pazopanib over a 60 day period who have not discontinued this therapy more than 100 days prior to study enrollment. Progressive disease per RECIST 1.1 guidelines will be preferred - Therapy with up to three prior systemic regimens will be allowed. - Patients may have been treated with any of the following: sorafenib, sunitinib, bevacizumab, pazopanib, temsirolimus, everolimus, interferon alpha, interleuken-2. - Treatment with up to one prior regimen that included cytotoxic chemotherapy will be allowed. - Patients may have been treated with more than 1 antiangiogenic therapy (e.g., patients may have been treated with both sorafenib and sunitinib or sunitinib and bevacizumab, or sequential combinations that include pazopanib). - Life expectancy of at least 3 months - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. - Tumor tissue must be available for correlative studies. - Patients must consent to allow the acquisition of formalin-fixed paraffin-embedded (FFPE) material (block or unstained slides) by study personnel for performance of correlative tissue studies. Exclusion Criteria: - Known brain metastases - Prior therapy with brivanib, or anti-FGFR (fibroblast growth factor receptor) therapy. - History of thrombotic or embolic events within the last six months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism. - Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE version 4.0 Grade greater than 3 within 30 days prior to study entry. - Uncontrolled or significant cardiovascular disease. - QTc greater than 450 msec on two consecutive ECGs (Baseline ECG should be repeated if QTc is found to be greater than 450 msec.). - Active infection, less than 7 days after completing systemic antibiotic therapy. - History of non-healing wounds or ulcers or bone fractures within 3 months of fracture. - Major surgical procedure, open biopsy, or significant traumatic injury less than 3 weeks prior to study enrollment or those who receive minor surgical procedures (e.g. core biopsy or fine needle aspiration)within 1 week prior to study enrollment. - Cytotoxic chemotherapy within 3 weeks, bevacizumab within 2 months, or radiation therapy within 2 weeks, other targeted therapies (e.g., sorafenib, sunitinib, temsirolimus, everolimus)within 2 days. - Inability to swallow tablets or untreated malabsorption syndrome. - Pre-existing thyroid abnormality with thyroid function that cannot be controlled with medication. - History of HIV - Patients with centrally cavitating lung lesions. - Patients requiring therapeutic anticoagulation with warfarin at baseline. However, prophylactic therapy with a low molecular weight heparin at baseline is acceptable.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Stephen Keefe, MD Principal Investigator Abramson Cancer Center of the University of Pennsylvania
Location
Facility: Abramson Cancer Center of the University of Pennsylvania
Location Countries

United States

Verification Date

2021-03-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Arm 1

Type: Experimental

Description: Patients receive oral brivanib alaninate daily in the absence of disease progression or unacceptable toxicity.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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