Last updated on July 2020

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


Brief description of study

Background
  • Papillary 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 VEGF pathway antagonists or mTOR inhibitors.
  • Activating mutations of 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 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 HGF/MET pathway will lead to clinical activity in patients with papillary renal cell cancer
    Objectives

Primary Objective:

-To determine the overall response rate (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
  • 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.

Detailed Study Description

Background
  • Papillary 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 VEGF pathway antagonists or mTOR inhibitors.
  • Activating mutations of 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 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 HGF/MET pathway will lead to clinical activity in patients with papillary renal cell cancer
    Objectives

Primary Objective:

-To determine the overall response rate (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
  • 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.

Clinical Study Identifier: NCT02019693

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Recruitment Status: Open


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