A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer

Kidney Cancer Clinical Trial

Official title: A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Kidney Cancer
• Kidney Neoplasms

• NCT number: NCT02019693
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 2
• Start date: January 24, 2014
• Completion date: December 17, 2021