- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01253668
Brivanib Metastatic Renal Cell Carcinoma
March 18, 2021 updated by: Abramson Cancer Center of the University of Pennsylvania
Brivanib (BMS-582664, Brivanib Alaninate) in Treatment of Refractory Metastatic Renal Cell Carcinoma - A Phase II Pharmacodynamic and Baseline Biomarker Study
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.
Study Overview
Status
Terminated
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
10
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
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Abramson Cancer Center of the University of Pennsylvania
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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
Genders Eligible for Study
All
Description
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.
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: Arm 1
Patients receive oral brivanib alaninate daily in the absence of disease progression or unacceptable toxicity.
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Brivanib by mouth daily at a dose of 800mg.
Undergo 1241-cG250 PET/CT imaging (correlative studies)
Other Names:
Undergo 124I-cG250 PET/CT imaging (correlative studies)
Undergo 1241-cG250 PET/CT imaging (correlative studies)
Correlative studies
correlative studies
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival (PFS)
Time Frame: 16 weeks
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All patients will be followed through the entire 16-week period and will be given a binary outcome assignment: progressive disease or not.
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16 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Best Overall Response Rated for Each Patients as Assessed by RECIST 1.1 Guidelines
Time Frame: Every 8 weeks
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The best overall radiographic response to therapy as measured and assessed using RECIST 1.1 guidelines will be captured for each research subject.
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Every 8 weeks
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Overall Survival
Time Frame: Every 8 weeks
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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.
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Every 8 weeks
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Change in Total Antibody Binding as Assessed by 124I-cG250 PET/CT Imaging (Correlative Studies)
Time Frame: At baseline and 8 weeks
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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.
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At baseline and 8 weeks
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Response Rate for All Patients
Time Frame: Every 8 weeks
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Response Rate for all patients as assessed by RECIST 1.1 guidelines
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Every 8 weeks
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Molecular Markers
Time Frame: At baseline
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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)
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At baseline
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Changes in Collagen IV Levels
Time Frame: At baseline and week 3
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Changes in collagen IV levels for each patient (correlative studies)
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At baseline and week 3
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Germline Polymorphisms and Assessment of Relationship to Toxicity and Clinical Outcome
Time Frame: At baseline and week 3
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Germline polymorphisms and assessment of relationship to toxicity and clinical outcome (correlative studies)
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At baseline and week 3
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Blood Pressure Data
Time Frame: At baseline, day 1 weeks 3,6,8,12,16 and every 6-8 weeks thereafter
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Blood pressure data
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At baseline, day 1 weeks 3,6,8,12,16 and every 6-8 weeks thereafter
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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
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Toxicity as assessed by NCI CTCAE version 4.0
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Day 1, weeks 3,6,9,12,16, and every 6-8 weeks thereafter
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
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)
November 1, 2011
Primary Completion (Actual)
September 1, 2013
Study Completion (Actual)
September 1, 2013
Study Registration Dates
First Submitted
November 30, 2010
First Submitted That Met QC Criteria
December 2, 2010
First Posted (Estimate)
December 3, 2010
Study Record Updates
Last Update Posted (Actual)
April 13, 2021
Last Update Submitted That Met QC Criteria
March 18, 2021
Last Verified
March 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Kidney Neoplasms
- Carcinoma, Renal Cell
- Carcinoma
- Physiological Effects of Drugs
- Immunologic Factors
- Antibodies
- Antibodies, Monoclonal
Other Study ID Numbers
- UPCC 04810
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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