Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2) — INTUITT-NF2  

Meningioma Clinical Trial

Official title: Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)

Status Recruiting

Clinical Trial 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

Clinical Trial 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.

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-overexpressed/amplified 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). ;

Related Conditions & MeSH terms

• Ependymoma
• Meningioma
• Neurilemmoma
• Neurofibroma
• Neurofibromatoses
• Neurofibromatosis 1
• Neurofibromatosis 2
• Neurofibromatosis Type 2
• Neuroma, Acoustic
• Non-vestibular Schwannoma
• Vestibular Schwannoma

• NCT number: NCT04374305
• Study type: Interventional
• Source: Massachusetts General Hospital
• Contact: Scott Plotkin, MD
• Phone: 617-643-8992
• Email: lmhibyan@mgb.org
• Status: Recruiting
• Phase: Phase 2
• Start date: June 20, 2020
• Completion date: December 2030