Ignite Creation Date:
2024-05-06 @ 2:38 PM
Last Modification Date:
2024-10-26 @ 1:34 PM
Study NCT ID:
NCT04374305
Status:
RECRUITING
Last Update Posted:
2024-03-13
First Post:
2020-04-30
Brief Title:
Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis INTUITT-NF2
Sponsor:
Scott R Plotkin MD PhD
Organization:
Massachusetts General Hospital
Study Overview
Official Title:
Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis INTUITT-NF2
Status:
RECRUITING
Status Verified Date:
2024-03
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:
INTUITT-NF2
Brief Summary:
This is a multi-arm phase II platform-basket screening study designed to test multiple experimental therapies simultaneously in patients with NF2-related schwannomatosis NF2-SWN formerly known as neurofibromatosis type 2 with associated progressive tumors of vestibular schwannomas VS non-vestibular schwannomas non-VS meningiomas and ependymomas
This Master Study is being conducted as a basket study that may allow people with multiple tumor types associated with NF2-SWN to receive new drugs throughout this study Embedded within the Master Study are individual drug substudies
Investigational Drug Sub-study A Brigatinib
Investigational Drug Sub-study B Neratinib
This Master Study is being conducted as a basket study that may allow people with multiple tumor types associated with NF2-SWN to receive new drugs throughout this study Embedded within the Master Study are individual drug substudies
Investigational Drug Sub-study A Brigatinib
Investigational Drug Sub-study B Neratinib
Detailed Description:
This research study is a Phase II clinical trial Phase II clinical trials test the safety and effectiveness of investigational drugs to learn whether the drugs works in treating a specific disease As a basket study the trial will enroll patients with NF2-SWN with associated progressive tumors of vestibular schwannomas VS non-vestibular schwannomas non-VS meningiomas and ependymomas
The MASTER STUDY is intended to enroll participants who will be allocated into different treatment arms SUB-STUDIES which will each have an additional consent and enrollment processes
MASTER STUDY
-- The research study procedures include screening for eligibility randomization to an experimental treatment sub-study if qualified and observation for up to 10 years
Participants who have tumors grow during a treatment sub-study will be permitted to enroll in a different experimental treatment sub-study if they are eligible
Participants who are not eligible for enrollment in a different treatment sub-study will be permitted to remain under observation on the Master Study to understand the growth pattern of these tumors natural history
Participants will be eligible to remain on this Master study for up to 10 years
It is expected that about 80 people will take part in the Master Study
The study will randomize a maximum of 40 patients to each of the experimental arms The overall size of the trial is not fixed by design because it include arm-dropping rules for futility and allow for the possibility of arm addition by amendment
SUB-STUDY A brigatinib Drug Sub-study A will test the activity of brigatinib for treatment of NF2-related tumors
Brigatinib is approved for the treatment of people with anaplastic lymphoma kinase ALK- positive metastatic non-small cell lung cancer NSCLC who have progressed or are intolerant to crizotinib In preclinical models brigatinib has shown evidence of activity against models of NF2-deficient tumors
Forty 40 people will take part in the Brigatinib Sub-study
The sub-study with brigatinib includes two stages
In Stage 1 20 subjects with any allowable tumor type will be accrued to each arm A minimum of 2 subjects per tumor type vestibular schwannoma non-vestibular schwannoma meningioma and ependymoma must be accrued in Stage 1 Interim analysis will be performed after Stage 1 to determine the radiographic response rate RR for each tumor types Subsequently in stage 2 another 20 subjects will be accrued into the 2 baskets with the most promising early results If the results are equally promising for more than 2 baskets subjects will be allocated to the appropriate number of baskets
SUB-STUDY B neratinib Collaborator National Comprehensive Cancer Network NCCN through a grant provided by Puma Biotechnology Drug Sub-study B will test the activity of neratinib for treatment of NF2-related tumors
Neratinib is approved for the treatment of people with early stage HER2-overexpressedamplified breast cancer following treatment with trastuzumab-based therapy In preclinical models neratinib has shown evidence of activity against models of NF2-deficient tumors
- It is expected that 20 people will take part in the Neratinib Sub-study A minimum of 2 subjects per tumor type vestibular schwannoma non-vestibular schwannoma meningioma and ependymoma must be accrued Analysis will be performed to determine the radiographic response rate RR for each tumor types
A subset of 5 participants will be enrolled into the PET imaging biomarker study These participants will have additional PET scans performed just prior to the first dose of neratinib and after starting the treatment witin 24 to 72 hours
The MASTER STUDY is intended to enroll participants who will be allocated into different treatment arms SUB-STUDIES which will each have an additional consent and enrollment processes
MASTER STUDY
-- The research study procedures include screening for eligibility randomization to an experimental treatment sub-study if qualified and observation for up to 10 years
Participants who have tumors grow during a treatment sub-study will be permitted to enroll in a different experimental treatment sub-study if they are eligible
Participants who are not eligible for enrollment in a different treatment sub-study will be permitted to remain under observation on the Master Study to understand the growth pattern of these tumors natural history
Participants will be eligible to remain on this Master study for up to 10 years
It is expected that about 80 people will take part in the Master Study
The study will randomize a maximum of 40 patients to each of the experimental arms The overall size of the trial is not fixed by design because it include arm-dropping rules for futility and allow for the possibility of arm addition by amendment
SUB-STUDY A brigatinib Drug Sub-study A will test the activity of brigatinib for treatment of NF2-related tumors
Brigatinib is approved for the treatment of people with anaplastic lymphoma kinase ALK- positive metastatic non-small cell lung cancer NSCLC who have progressed or are intolerant to crizotinib In preclinical models brigatinib has shown evidence of activity against models of NF2-deficient tumors
Forty 40 people will take part in the Brigatinib Sub-study
The sub-study with brigatinib includes two stages
In Stage 1 20 subjects with any allowable tumor type will be accrued to each arm A minimum of 2 subjects per tumor type vestibular schwannoma non-vestibular schwannoma meningioma and ependymoma must be accrued in Stage 1 Interim analysis will be performed after Stage 1 to determine the radiographic response rate RR for each tumor types Subsequently in stage 2 another 20 subjects will be accrued into the 2 baskets with the most promising early results If the results are equally promising for more than 2 baskets subjects will be allocated to the appropriate number of baskets
SUB-STUDY B neratinib Collaborator National Comprehensive Cancer Network NCCN through a grant provided by Puma Biotechnology Drug Sub-study B will test the activity of neratinib for treatment of NF2-related tumors
Neratinib is approved for the treatment of people with early stage HER2-overexpressedamplified breast cancer following treatment with trastuzumab-based therapy In preclinical models neratinib has shown evidence of activity against models of NF2-deficient tumors
- It is expected that 20 people will take part in the Neratinib Sub-study A minimum of 2 subjects per tumor type vestibular schwannoma non-vestibular schwannoma meningioma and ependymoma must be accrued Analysis will be performed to determine the radiographic response rate RR for each tumor types
A subset of 5 participants will be enrolled into the PET imaging biomarker study These participants will have additional PET scans performed just prior to the first dose of neratinib and after starting the treatment witin 24 to 72 hours
Study Oversight
Has Oversight DMC:
None
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?:
None