Background:~Papillary Renal Cell Cancer (RCC) is the second most common histologic subtype of kidney cancer, accounting for approximately 10-15% of cases~Type 1 papillary RCC occurs in both sporadic and hereditary forms, which are histologically identical. Non familial type 1 papillary RCC can present as both solitary renal tumors and as bilateral, multifocal disease~There are no standard agents of proven efficacy for patients with advanced papillary~RCC.~Patients with disease localized to the kidney are managed surgically while patients with advanced/unresectable disease are usually managed in the community with vascular endothelial growth factor (VEGF) pathway antagonists or mechanistic target of rapamycin (mTOR) inhibitors.~Activating mutations of mesenchymal epithelial transition (MET) were identified in the germline of affected HPRC patients, who have a predilection for the development of bilateral, multifocal type 1 papillary RCC. Somatic MET mutations have been found in a subset of patients with non-inherited, sporadic papillary renal carcinoma~The investigational agent Capmatinib (INC280) is a selective MET inhibitor lacking activity against the VEGF pathway~This is a proof-of-concept study using INC280 in patients with papillary RCC to test the idea that effectively blocking the hepatocyte growth factor (HGF)//MET pathway will lead to clinical activity in patients with papillary renal cell cancer~Objectives:~Primary Objective:~-To determine the overall response rate (Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) in patients with papillary renal cell carcinoma treated with single agent INC280~Eligibility:~Diagnosis of hereditary papillary renal carcinoma (HPRC) or sporadic papillary renal cell carcinoma (RCC)~Patients with bilateral multifocal disease can have tumors localized to the kidney or have metastatic disease~Patients with sporadic papillary RCC (but without multifocal disease) should have advanced disease that is considered unresectable~Eastern Cooperative Oncology Group (ECOG) 0-2~Measurable disease~Adequate organ function~No active brain metastases~Prior therapy~No more than 3 prior lines of systemic therapy~Prior therapy with a MET inhibitor is allowed as long as the patient has not had progressive disease while receiving the agent~Design:~This is a phase 2 single center non-randomized trial.~The study will be conducted using a Simon 2 stage minimax design. Initially 13 evaluable subjects will be recruited. If there are no responses to therapy, the study will be terminated. If there is at least 1 response an additional 7 evaluable subjects will be accrued.~The two-stage minimax design is based on assuming an ineffective response rate of 5% and a targeted effective response rate of 25%. We also assume that the probability of accepting an ineffective treatment and the probability of rejecting an effective treatment are each 10%.~Subjects will be dosed orally at a starting dose of 400 mg twice daily.~The overall response rate (complete response + partial response) will be determined.
Background:~Papillary Renal Cell Cancer (RCC) is the second most common histologic subtype of kidney cancer, accounting for approximately 10-15% of cases~Type 1 papillary RCC occurs in both sporadic and hereditary forms, which are histologically identical. Non familial type 1 papillary RCC can present as both solitary renal tumors and as bilateral, multifocal disease~There are no standard agents of proven efficacy for patients with advanced papillary~RCC.~Patients with disease localized to the kidney are managed surgically while patients with advanced/unresectable disease are usually managed in the community with vascular endothelial growth factor (VEGF) pathway antagonists or mechanistic target of rapamycin (mTOR) inhibitors.~Activating mutations of mesenchymal epithelial transition (MET) were identified in the germline of affected hereditary papillary renal cancer (HPRC) patients, who have a predilection for the development of bilateral, multifocal type 1 papillary RCC. Somatic MET mutations have been found in a subset of patients with non-inherited, sporadic papillary renal carcinoma~The investigational agent Capmatinib (INC280) is a selective MET inhibitor lacking activity against the VEGF pathway~This is a proof-of-concept study using INC280 in patients with papillary RCC to test the idea that effectively blocking the hepatocyte growth factor (HGF)/MET pathway will lead to clinical activity in patients with papillary renal cell cancer~Objectives:~Primary Objective:~-To determine the overall response rate (Response Evaluation Criteria in Solid Tumors (RECIST) 1.1) in patients with papillary renal cell carcinoma treated with single agent INC280~Eligibility:~Diagnosis of hereditary papillary renal carcinoma (HPRC) or sporadic papillary renal cell carcinoma (RCC)~Patients with bilateral multifocal disease can have tumors localized to the kidney or have metastatic disease~Patients with sporadic papillary RCC (but without multifocal disease) should have advanced disease that is considered unresectable~Eastern Cooperative Oncology Group (ECOG) 0-2~Measurable disease~Adequate organ function~No active brain metastases~Prior therapy~No more than 3 prior lines of systemic therapy~Prior therapy with a MET inhibitor is allowed as long as the patient has not had progressive disease while receiving the agent~Design:~This is a phase 2 single center non-randomized trial.~The study will be conducted using a Simon 2 stage minimax design. Initially 13 evaluable subjects will be recruited. If there are no responses to therapy, the study will be terminated. If there is at least 1 response an additional 7 evaluable subjects will be accrued.~The two-stage minimax design is based on assuming an ineffective response rate of 5% and a targeted effective response rate of 25%. We also assume that the probability of accepting an ineffective treatment and the probability of rejecting an effective treatment are each 10%.~Subjects will be dosed orally at a starting dose of 600 mg twice daily.~The overall response rate (complete response + partial response) will be determined.