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).
This randomized phase II trial studies how well cabozantinib-s-malate, crizotinib, volitinib, or sunitinib malate work in treating patients with kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Cabozantinib-s-malate, crizotinib, volitinib, and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
* Patients must have histologically or cytologically confirmed papillary histology renal cell carcinoma which is metastatic or locally advanced disease not amenable to surgical resection; (NOTE: a designation of type I or type II should be made by the local pathologist if possible) mixed histologies containing type I or type II will be allowed provided that they contain >= 50% of the papillary component
* Patients must also have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
* Patients with a history of treated brain metastases who are asymptomatic and have not received steroid therapy in the 14 days prior to registration are eligible; anti-seizure medications are allowed provided they are non-enzyme inducing (e.g. topiramate, levetiracetam, gabapentin)
* Patients must not have cavitating pulmonary lesions; patients must not have tumor invading the gastrointestinal (GI) tract or evidence of endotracheal or endobronchial tumor within 28 days prior to registration
* Patients may have received prior surgery; at least 28 days must have elapsed since surgery and patient must have recovered from any adverse effects of surgery
* Patients may have received up to one prior systemic therapy for advanced or metastatic renal cell carcinoma; if a patient develops metastatic disease within six months of discontinuation of adjuvant therapy, this will constitute one prior systemic therapy for advanced or metastatic renal cell carcinoma (RCC); if a patient develops metastatic disease and more than six months has elapsed since discontinuation of adjuvant therapy, this will not constitute prior systemic therapy for advanced or metastatic RCC; patients must not have received a MET/hepatocyte growth factor (HGF) inhibitor or sunitinib as prior therapy; at least 14 days must have elapsed since completion of prior systemic therapy; patients must have recovered from all associated toxicities at the time of registration
* Patients may have received prior radiation therapy, but must have measurable disease outside the radiation port; at least 14 days must have elapsed since completion of prior radiation therapy; patients must have recovered from all associated toxicities at the time of registration
* Patients must not be taking, nor plan to take while on protocol treatment, strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, voriconazole, posaconazole, fluvoxamine, nefazodone, nelfinavir, ritonavir) and/or strong CYP3A4 inducers (e.g. phenytoin, rifampin, rifabutin) within 14 days prior to randomization; moderate inhibitors or inducers of isoenzyme CYP3A4 should be avoided, but if necessary can be used with caution
* Patients must not demonstrate any other signs indicative of pulmonary hemorrhage within 3 months prior to registration
* Patient's baseline imaging must not indicate the presence of tumor invading or encasing any major blood vessels
Gary Goodman, M.D.
SWOG (Southwest Oncology Group)
The Pacific Cancer Research Consortium clinical trials are offered at multiple locations throughout Oregon, Washington, Alaska, California, and Idaho. To find a location near you, please contact the Patient Engagement Center at 844-552-2734.