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