Intervention: Brivanib alaninate
Trial phase: Phase 2
SMILES: Cc1cc2c(F)c(Oc3ncnn4cc(OC[C@@H](C)OC(=O)[C@H](C)N)c(C)c34)ccc2[nH]1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 10
Group description: Patients receive oral brivanib alaninate daily in the absence of disease progression or unacceptable toxicity.

Brivanib alaninate: Brivanib by mouth daily at a dose of 800mg.

Polymerase chain reaction: Undergo 1241-cG250 PET/CT imaging (correlative studies)

Iodine I 124 chimeric monoclonal antibody G250: Undergo 124I-cG250 PET/CT imaging (correlative studies)

Positron emission tomography/computed tomography: Undergo 1241-cG250 PET/CT imaging (correlative studies)

Protein expression analysis: Correlative studies

Immunohistochemistry: correlative studies
Eligibility 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 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.