Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (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
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 drug(s) 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.