A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer
Status:
Active, not recruiting
Trial end date:
2023-06-30
Target enrollment:
Participant gender:
Summary
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.