Brivanib Metastatic Renal Cell Carcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01253668
First received: November 30, 2010
Last updated: December 4, 2012
Last verified: February 2012

November 30, 2010
December 4, 2012
November 2010
December 2012   (final data collection date for primary outcome measure)
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.
Progression Free Survival (PFS) [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
All patients will be followed through the entire 16-week period and will be given a binary outcome assignment: progressive disease or not.
Complete list of historical versions of study NCT01253668 on ClinicalTrials.gov Archive Site
  • 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
  • Best overall response rate [ Designated as safety issue: Yes ]
    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 [ Designated as safety issue: Yes ]
    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.
  • I-cG250 PET/CT [ Designated as safety issue: Yes ]
    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.
Not Provided
Not Provided
 
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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
    Brivanib by mouth daily at a dose of 800mg.
  • Genetic: Polymerase chain reaction
    Undergo 1241-cG250 PET/CT imaging (correlative studies)
    Other Name: PCR
  • Other: 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 studies
  • Other: Immunohistochemistry
    correlative studies
    Other Name: immunohistochemistry staining method
Experimental: Arm 1
Patients receive oral brivanib alaninate daily in the absence of disease progression or unacceptable toxicity.
Interventions:
  • 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
  • Other: Immunohistochemistry
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
December 2012
December 2012   (final data collection date for primary outcome measure)

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 measureable 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 priorregimen that included cytotoxiv 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
  • ECOG performance status of 0 or 1.
  • Tumor tissue must be available for correlative studies.
  • Patients must consent to allow the acquisition of 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.
  • Gastointestinal bleeding or any other hemmorrhage/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., sorefenib, sunitinib, temsirolimus, everolimus)within 2 days.
  • Inability to swallow tabletsor 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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01253668
UPCC 04810
Yes
Abramson Cancer Center of the University of Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Not Provided
Principal Investigator: Stephen Keefe, MD Abramson Cancer Center of the University of Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP