A Randomized, Phase II Efficacy Assessment of Multiple MET Kinase Inhibitors (Cabozantinib [NSC #761968], Crizotinib [NSC #749005], Savolitinib [NSC #785348], and Sunitinib [NSC #736511])in Metastatic Papillary Renal Carcinoma (PAPMET)

Histologically or cytologically confirmed papillary histology renal cell carcinoma that is metastatic or locally advanced disease not amenable to surgical resection. Measurable disease. Eval for tumor measurement within 28 days prior to reg. Bone scan if suspicion for bone mets. No cavitating pulmonary lesions. No tumor invading the GI tract or evidence of endotracheal or endobronchial tumor within 28 days prior to reg. May have received prior surgery. May have received up to one prior systemic therapy for advanced or metastatic renal cell carcinoma with the exception of another VEGF inhibitor FDA-approved for advanced RCC. See Section 5.2.b for details. May have received prior radiation therapy but must have measurable disease outside the radiation port. Must not be taking strong CYP3A4 inhibitors, strong CYP3A4 inducers, potent inhibitors of CYP1A2, or drugs known to be CYP3A4 substrates with a narrow therapeutic range. Not receiving any other investigational agents. Within 28 days prior to reg: complete physical exam and medical history; adequate hematologic function; adequate hepatic function; adequate kidney function; echocardiogram; EKG; baseline urinalysis; electrolytes. Zubrod 0-1. No clinical evidence of CHF at reg. No unstable angina pectoris, clinically significant cardiac arrhythmias, or stroke within 3 months prior to reg. No myocardial infarction or thromboembolic event requiring anticoagulation with 6 months prior to reg. No inadequately controlled hypertension. Must be able to take orals meds. No clinically-significant GI bleeding within 6 months prior to reg. No GI disorder that bears a high risk of perforation or fistula. No hemoptysis within 3 months prior to reg. No signs of pulmonary hemorrhage within 3 months prior to reg. Imaging must not indicate the presence of tumor invading or encasing any major blood vessels. Not pregnant or nursing. No combination antiretroviral therapy. Must have tissue available and be willing to submit for central path review.