A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer
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|ClinicalTrials.gov Identifier: NCT02019693|
Recruitment Status : Recruiting
First Posted : December 24, 2013
Last Update Posted : May 3, 2018
- 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
- 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
-To determine the overall response rate (RECIST 1.1) in patients with papillary renal cell carcinoma treated with single agent INC280
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
- 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
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Papillary Renal Cell Carcinoma||Drug: INC280||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer|
|Study Start Date :||December 20, 2013|
|Estimated Primary Completion Date :||January 1, 2019|
|Estimated Study Completion Date :||January 1, 2019|
Experimental: Single arm
INC280 400 mg twice every day by mouth, continuously
Supplied by Novartis as film-coated tablet for oral use.
- Overall response rate [ Time Frame: 4-5 years ]
- Progression-free survival, overall survival, disease control rate and duration of response, tolerability [ Time Frame: 4-5 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02019693
|Contact: Martha Ninos, R.N.||(301) firstname.lastname@example.org|
|Contact: Ramaprasad Srinivasan, M.D.||(240) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Ramaprasad Srinivasan, M.D.||National Cancer Institute (NCI)|