Ignite Creation Date:
2025-12-25 @ 1:11 AM
Ignite Modification Date:
2025-12-25 @ 11:22 PM
Study NCT ID:
NCT02019693
Status:
COMPLETED
Last Update Posted:
2023-03-21
First Post:
2013-12-20
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer
Status:
COMPLETED
Status Verified Date:
2023-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
* 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.
Detailed 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.
* 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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 14-C-0037 | None | None | View |