Kidney CancerPhase 2NCT02019693
A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer
A Phase 2 study testing INC280 in people with Kidney Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Cancer
- What is being tested?
- INC280
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jan 2014to 17 Dec 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 2.1.1.1 Patients must have histologically or cytologically confirmed papillary Renal Cell Cancer (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
- 2.1.1.2 Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions). Nodal lesions must be 15mm by computed tomography (CT) scan or magnetic resonance imaging (MRI). Non nodal lesions must be >10 mm with CT scan or MRI.
- 2.1.1.3 Patients must have normal organ and marrow function as defined below:
- Hemoglobin > 9 g/dL (SI Units: 90 g/L)
Show all 20Show fewer
- Platelet count greater than or equal to 75 x 10 (9)/L
- Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10(9)/L without growth factor support
- Total bilirubin less than or equal to 2 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamate-pyruvate transaminase (SGPT) less than or equal to 2.5 x upper limit of normal (ULN)
- Serum creatinine less than or equal to 1.5 x ULN
- Asymptomatic serum amylase less than or equal to 2 x ULN; patients with > ULN but less than or equal to 2 x ULN serum amylase at study start must be confirmed to have no signs and/or symptoms suggestion pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging findings of pancreas, etc.)
- Serum lipase less than or equal to ULN
- Fasting serum triglyceride level less than or equal to 500 mg/dL
- 2.1.1.4 Patients may have had no more than 3 prior lines of systemic therapy. Prior therapy with a mesenchymal epithelial transition (MET) inhibitor is allowed as long as the patient has not had progressive disease while receiving the agent
- 2.1.1.5 Patient must be able to swallow and retain oral medication
- 2.1.1.6 Age greater than or equal to18 years.
- 2.1.1.7 Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
- 2.1.1.8 Patients must provide written informed consent prior to any study procedures.
- 2.1.1.9 Patients must be willing and able to comply with scheduled visits, treatment plan and laboratory tests
Who cannot join
- 2.1.2.1 Patients who are receiving any other investigational agents for treatment of their kidney cancer.
- 2.1.2.2 History of allergic reactions attributed to compounds of similar chemical or biologic composition to Capmatinib (INC280). Excipients in the current formulation include microcrystalline cellulose, mannitol, sodium starch glycolate, magnesium stearate and colloidal silicon dioxide
- 2.1.2.3 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or potentially affect the interpretation of study data.
- 2.1.2.4 Subjects with significant or uncontrolled cardiovascular disease (e.g., uncontrolled hypertension, peripheral vascular disease, congestive heart failure, cardiac arrhythmia, or acute coronary syndrome) within 6 months prior to starting study treatment or heart attack within 12 months prior to starting study treatment
- 2.1.2.5 Patients receiving any medications that are known to be strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4), or sensitive substrates of CYP3A4, cytochrome P450 1A2 (CYP1A2), cytochrome P450 family 2 subfamily C member 9 (CYP2C9), cytochrome P450 2C19 (CYP2C19) or P-glycoprotein (P-gp) with a narrow therapeutic index.
- 2.1.2.6 Symptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring > 5 mg/day of dexamethasone (or equivalent) to control CNS disease.
Show all 24Show fewer
- Note: Patients with controlled CNS metastases are allowed. Radiotherapy or surgery for CNS metastases must have been completed >2 weeks prior to study entry. Patients must be neurologically stable, having no new neurologic deficits on clinical examination, and no new findings on CNS imaging. Steroid use for management of CNS metastases must be at a stable dose for two weeks preceding study entry.
- 2.1.2.7 Patients with greater than or equal to Grade 2 neuropathy.
- 2.1.2.8 Treatment with proton pump inhibitors within 3 days prior to study entry. If continued use of gastrointestinal (GI) prophylaxis is required, the patient will be switched to an appropriate Histamine H2-receptor antagonists (H2) with appropriate counsel and caution.
- 2.1.2.9 Currently receiving any prohibited medications including vitamins and herbal Supplements.
- 2.1.2.10 Major surgery within 4 weeks prior to initiating treatment, excluding the placement of vascular access.
- 2.1.2.11 The subject has not recovered to baseline, Common Terminology Criteria for Adverse Events (CTCAE) less than or equal to Grade 1 from toxicity due to all prior therapies for RCC or to a level permitted under other sections of the eligibility criteria except alopecia and other non-clinically significant adverse events (AEs).
- 2.1.2.12 Any other condition that would, in the Investigators judgment, contraindicate participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.
- 2.1.2.13 Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 30 mIU/mL). Laboratory values >5 mIU/mL, but <30 mIU/mL should be repeated in 48 hours.
- 2.1.2.14 Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months days after stopping study drug. Highly effective contraception methods include:
- Total abstinence or
- Male or female sterilization or
- Combination of any two of the following (a+b or a+c or b+c):
- Use of oral, injected or implanted hormonal methods of contraception
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential.
- 2.1.2.15 Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping study drug and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
- 2.1.2.16 Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Capmatinib (INC280).
- 2.1.2.17 Prior invasive malignancy of other histology currently requiring treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
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
Read more
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.
Read the 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.
- Conditions
- Kidney Cancer
- Being tested
- INC280
- Keywords
- Hereditary Papillary Renal Cell Carcinoma, VEGF Pathway, mTOR Inhibitor, Kidney Cancer
- Medical subject headings
- Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INC280Drug
Also called Capmatinib
Supplied by Novartis as film-coated tablet for oral use.
| Study group | Role | What they receive |
|---|---|---|
| Capmatinib (INC280) | Experimental | INC280 400 mg twice every day by mouth, continuously Receives: Drug: INC280 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Response
Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: From start of study until permanent treatment discontinuation (range 2 weeks-238 weeks)
Secondary outcomes (4)
Progression Free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.
Measured: Median 26.8 months
Overall Survival
OS is the time between the first day of treatment and day of death or last follow up calculated by Kaplan Meier analysis.
Measured: Median 26.8 months
Disease Control Rate (Partial and Complete Response Plus Stable Disease > 6 Months)
Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: From start of study until permanent treatment discontinuation (range 2 weeks-238 weeks)
Number of Grades 1-5 Adverse Events Related to Treatment
Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
Measured: Date treatment consent signed to date off study, approximately 94 months and 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2013 (estimated)
- Study start24 Jan 2014
- Primary completion17 Dec 2021
- Study completion17 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Kidney CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Ramaprasad Srinivasan, M.D., National Cancer Institute (NCI)
- Investigators
- Ramaprasad Srinivasan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02019693
- Sponsor's protocol ID
- 140037
- Other IDs
- 14-C-0037
- Status last verified
- Mar 2023
- First submitted
- 20 Dec 2013
- Last updated
- 21 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer
- ClinicalTrials.gov ID
- NCT02019693
- Acronym / sponsor ID
- 140037
- Conditions
- Kidney Cancer
- Keywords
- Hereditary Papillary Renal Cell Carcinoma, VEGF Pathway, mTOR Inhibitor, Kidney Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 24 Jan 2014 (actual)
- Primary completion
- 17 Dec 2021 (actual)
- Study completion
- 17 Dec 2021 (actual)
- First posted
- 24 Dec 2013 (estimated)
- Results
- Posted 21 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Capmatinib (INC280) | Experimental | Drug: INC280INC280 400 mg twice every day by mouth, continuously |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 2.1.1.1 Patients must have histologically or cytologically confirmed papillary Renal Cell Cancer (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
- 2.1.1.2 Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions). Nodal lesions must be 15mm by computed tomography (CT) scan or magnetic resonance imaging (MRI). Non nodal lesions must be >10 mm with CT scan or MRI.
- Hemoglobin > 9 g/dL (SI Units: 90 g/L)
Key exclusion criteria (24 listed)
- 2.1.2.1 Patients who are receiving any other investigational agents for treatment of their kidney cancer.
- 2.1.2.2 History of allergic reactions attributed to compounds of similar chemical or biologic composition to Capmatinib (INC280). Excipients in the current formulation include microcrystalline cellulose, mannitol, sodium starch glycolate, magnesium stearate and colloidal silicon dioxide
- 2.1.2.3 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or potentially affect the interpretation of study data.
- 2.1.2.4 Subjects with significant or uncontrolled cardiovascular disease (e.g., uncontrolled hypertension, peripheral vascular disease, congestive heart failure, cardiac arrhythmia, or acute coronary syndrome) within 6 months prior to starting study treatment or heart attack within 12 months prior to starting study treatment
- 2.1.2.5 Patients receiving any medications that are known to be strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4), or sensitive substrates of CYP3A4, cytochrome P450 1A2 (CYP1A2), cytochrome P450 family 2 subfamily C member 9 (CYP2C9), cytochrome P450 2C19 (CYP2C19) or P-glycoprotein (P-gp) with a narrow therapeutic index.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INC280Also: CapmatinibSupplied by Novartis as film-coated tablet for oral use. | Drug | Capmatinib (INC280) |
Primary outcome
Percentage of Participants With Response
Time frame: From start of study until permanent treatment discontinuation (range 2 weeks-238 weeks)
Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
4 secondary outcomes
Progression Free Survival (PFS)
Time frame: Median 26.8 months
Overall Survival
Time frame: Median 26.8 months
Disease Control Rate (Partial and Complete Response Plus Stable Disease > 6 Months)
Time frame: From start of study until permanent treatment discontinuation (range 2 weeks-238 weeks)
Number of Grades 1-5 Adverse Events Related to Treatment
Time frame: Date treatment consent signed to date off study, approximately 94 months and 21 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ramaprasad Srinivasan, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing INC280 in people with Kidney Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Response (time frame: From start of study until permanent treatment discontinuation (range 2 weeks-238 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2023.