Brivanib Metastatic Renal Cell Carcinoma
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.
Male and Female Subjects 18 Years of Age and Older With Metastatic Renal Cell Carcinoma. Eligible Patients Must Have Undergone and Failed Prior Treatment.
Drug: Brivanib alaninate
Genetic: Polymerase chain reaction
Other: Iodine I 124 chimeric monoclonal antibody G250
Procedure: Positron emission tomography/computed tomography
Genetic: Protein expression analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Brivanib (BMS-582664, Brivanib Alaninate) in Treatment of Refractory Metastatic Renal Cell Carcinoma - A Phase II Pharmacodynamic and Baseline Biomarker Study|
- Progression Free Survival (PFS) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]All patients will be followed through the entire 16-week period and will be given a binary outcome assignment: progressive disease or not.
- Best overall response rate dfor each patients as assessed by RECIST 1.1 guidelines [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]The best overall radiographic response to therapy as measured and assessed using RECIST 1.1 guidelines will be captured for each research subject.
- Overall survival [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]Will record deaths on study, and, to the extent possible, after the study follow-up period is completed for each patient, will be captured. Reason for death will be identified and recorded where possible.
- Change in total antibody binding as assessed by 124I-cG250 PET/CT imaging (correlative studies) [ Time Frame: At baseline and 8 weeks ] [ Designated as safety issue: No ]Will determine the baseline and change in total antibody binding in lesions from baseline to the time on treatment that patients are assessed. The analysis dataset will be quantitated radiotracer uptake data obtained via I-cG250 PET/CT for all evaluable patients who complete the trial.
- Response rate for all patients [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]Response Rate for all patients as assessed by RECIST 1.1 guidelines
- Molecular markers [ Time Frame: At baseline ] [ Designated as safety issue: No ]Molecular markers expressed in patient tumor specimens as assessed by IHC and histocytometry (e.g., VHL, HIF, p-STAT3, p-ERK, and Ki67, VEGFR2, and FGFR1) (correlative studies)
- Changes in collagen IV levels [ Time Frame: At baseline and week 3 ] [ Designated as safety issue: No ]Changes in collagen IV levels for each patient (correlative studies)
- Germline polymorphisms and assessment of relationship to toxicty and clinical outcome [ Time Frame: At baseline and week 3 ] [ Designated as safety issue: No ]Germline polymorphisms and assessment of relationship to toxicity and clinical outcome (crrelative studies)
- Blood pressure data [ Time Frame: At baseline, day 1 weeks 3,6,8,12,16 and every 6-8 weeks thereafter ] [ Designated as safety issue: No ]Blood pressure data
- Toxicity as assessed by NCI CTCAE version 4.0 [ Time Frame: Day 1, weeks 3,6,9,12,16, and every 6-8 weeks thereafter ] [ Designated as safety issue: Yes ]Toxicity as assessed by NCI CTCAE version 4.0
|Study Start Date:||November 2010|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
Patients receive oral brivanib alaninate daily in the absence of disease progression or unacceptable toxicity.
Drug: Brivanib alaninate
Brivanib by mouth daily at a dose of 800mg.Genetic: Polymerase chain reaction
Undergo 1241-cG250 PET/CT imaging (correlative studies)
Other Name: PCROther: Iodine I 124 chimeric monoclonal antibody G250
Undergo 124I-cG250 PET/CT imaging (correlative studies)Procedure: Positron emission tomography/computed tomography
Undergo 1241-cG250 PET/CT imaging (correlative studies)Genetic: Protein expression analysis
Correlative studiesOther: Immunohistochemistry
Other Name: immunohistochemistry staining method
The primary objectiveof 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 whi 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 VHL and HIF expression assessment and a novel 'histocytometric' 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.
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Stephen Keefe, MD||Abramson Cancer Center of the University of Pennsylvania|