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


Phase 2
18 Years
N/A
Not Enrolling
Both
Male and Female Subjects 18 Years of Age and Older With Metastatic Renal Cell Carcinoma. Eligible Patients Must Have Undergone and Failed Prior Treatment.

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Trial Information

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


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.


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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival (PFS)

Outcome Description:

All patients will be followed through the entire 16-week period and will be given a binary outcome assignment: progressive disease or not.

Outcome Time Frame:

16 weeks

Safety Issue:

No

Principal Investigator

Stephen Keefe, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania

Authority:

United States: Food and Drug Administration

Study ID:

UPCC 04810

NCT ID:

NCT01253668

Start Date:

November 2010

Completion Date:

December 2012

Related Keywords:

  • Male and Female Subjects 18 Years of Age and Older With Metastatic Renal Cell Carcinoma. Eligible Patients Must Have Undergone and Failed Prior Treatment.
  • Carcinoma
  • Carcinoma, Renal Cell

Name

Location

Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283