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
  Purpose

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.


Condition Intervention Phase
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
Other: Immunohistochemistry
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Abramson Cancer Center of the University of Pennsylvania:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 30
Study Start Date: November 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: 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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01253668

Locations
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Investigators
Principal Investigator: Stephen Keefe, MD Abramson Cancer Center of the University of Pennsylvania
  More Information

No publications provided

Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01253668     History of Changes
Other Study ID Numbers: UPCC 04810
Study First Received: November 30, 2010
Last Updated: December 4, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014