Patient case: 65-year-old female with squamous cell lung cancer; genetic feature: FGFR1 amplification

Clinical trial: Brivanib Metastatic Renal Cell Carcinoma

Summary: 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.

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: 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.

Relevance to patient case: not relevant