Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
INTUITT-NF2
1 other identifier
interventional
109
1 country
6
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
- Investigational Drug Sub-study C: Retifanlimab plus bevacizumab
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jun 2020
Longer than P75 for phase_2
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 30, 2020
CompletedFirst Posted
Study publicly available on registry
May 5, 2020
CompletedStudy Start
First participant enrolled
June 20, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2030
May 6, 2026
May 1, 2026
9.5 years
April 30, 2020
May 4, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Radiographic response rate (for each drug substudy)
Radiographic response rates in target tumors according to tumor-associated criteria: * VS, non-VS, and meningiomas: Dombi criteria (2013) * Ependymomas: RECIST 1.12
2 years
Secondary Outcomes (1)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability
2 years
Study Arms (3)
Sub-study A (brigatinib) - CLOSED TO ENROLLMENT
EXPERIMENTALSubjects treated in this arm will receive brigatinib 90 mg by mouth daily for 7 days and then increased to 180 mg by mouth daily if the drug is tolerated.
Sub-study B (neratinib)
EXPERIMENTALThe first three participants treated in this arm will receive neratinib 200 mg mg by mouth daily. If these participants tolerate the medication well, subsequent participants will receive neratinib 240 mg by mouth daily.
Experimental: sub-study C (retifanlimab plus bevacizumab)
EXPERIMENTALSubjects on this arm will receive retifanlimab by IV infusion at a dose of 375 mg every 3 weeks on a continuous schedule for 48 weeks. Subjects will also receive bevacizumab by IV infusion at a dose of 7.5 mg/kg every 3 weeks on an intermittent schedule. One cycle last 42 days and the study will last for 52 total weeks (48 treatment weeks and 4 follow-up weeks).
Interventions
Every 3 weeks by IV per predetermined dose in protocol.
Every 3 weeks by IV per predetermined dose in protocol.
Oral daily per predetermined dosage per protocol.
Oral daily per predetermined dosage per protocol.
Eligibility Criteria
You may qualify if:
- \- Patients must have a pathogenic variant in the NF2 gene (either in the germline or in two NF2-related tumors) OR a confirmed diagnosis of NF2 by fulfilling National Institute of Health (NIH) criteria or Manchester criteria:
- The NIH criteria includes presence of:
- Bilateral vestibular schwannomas, OR
- First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity.
- The Manchester criteria includes presence of:
- Bilateral vestibular schwannomas, OR
- First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR
- Unilateral vestibular schwannoma AND any two of: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR
- Multiple meningiomas (two or more) AND unilateral vestibular schwannoma OR any two of: schwannoma, glioma, neurofibroma, cataract.
- Subjects must have a target NF2-related tumor (VS, non-VS, meningioma, or ependymoma) with documented radiographic progression within the preceding 36 months of Master Study registration defined as either:
- at least 20% increase in volume of enhancing tumor
- at least 2 mm increase in greatest linear dimension of enhancing tumor
- Participants must have measurable disease, defined as:
- VS, non-VS, or meningioma target lesions that can be accurately measured as at least 1 ml by volumetric MRI scan or in at least one dimension as ≥10 mm with conventional MRI scan. See protocol for the evaluation of measurable disease
- Ependymoma target lesions measurable linearly.
- +3 more criteria
You may not qualify if:
- Participants who have had chemotherapy within a minimum of 4 weeks prior to Master Study registration (or a minimum of 5 half-lives and resolution to baseline of toxicities unless there are irreversible toxicities from prior drug that do not influence risk of next drug).
- Participants who have received radiation to the target tumor within the last 3 years prior to Master study registration.
- Participants who are receiving any other investigational agents.
- Participants with target or non-target nervous system tumors that, in the opinion of the treating investigator, are likely to require active treatment (including surgery) within 6 months of registration to the Master Study.
- History of a different malignancy, unless (a) have been disease-free for at least 2 years and are deemed by the treating investigator to be at low risk for recurrence of that malignancy.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because the experimental agents may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these experimental agents, breastfeeding should be discontinued if the mother is treated.
- Eligibility Criteria Specific to SUB-STUDY A (Brigatinib arm): CLOSED TO ENROLLMENT
- Participants must meet all eligibility criteria outlined in the Master Study
- Participants must be willing and able to provide written informed consent/assent for the brigatinib arm of the INTUITT-NF2 trial.
- Participant is ≥ 12 years of age and has body weight at least 40 kg on Day 1 of treatment.
- Patient must be able to swallow pills.
- Clinical laboratory values as specified below within 28 days before the first dose of study drug, as described in the protocol document:
- Female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age group and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below:
- Female patients must meet 1 of the following:
- +111 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Incyte Corporationcollaborator
- Scott R. Plotkin, MD, PhDlead
- Takedacollaborator
- The Children's Tumor Foundationcollaborator
- National Comprehensive Cancer Networkcollaborator
Study Sites (6)
UCLA Medical Center
Los Angeles, California, 90095, United States
University of Miami
Miami, Florida, 33136, United States
Indiana University School of Medicine
Indianopolis, Indiana, 46202, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital
Boston, Massachusetts, 02115, United States
New York University Langone Medical Center
New York, New York, 10016, United States
Related Publications (1)
Plotkin SR, Yohay KH, Nghiemphu PL, Dinh CT, Babovic-Vuksanovic D, Merker VL, Bakker A, Fell G, Trippa L, Blakeley JO; INTUITT-NF2 Consortium. Brigatinib in NF2-Related Schwannomatosis with Progressive Tumors. N Engl J Med. 2024 Jun 27;390(24):2284-2294. doi: 10.1056/NEJMoa2400985. Epub 2024 Jun 21.
PMID: 38904277DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Scott Plotkin, MD
Massachusetts General Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Sponsor Investigator
Study Record Dates
First Submitted
April 30, 2020
First Posted
May 5, 2020
Study Start
June 20, 2020
Primary Completion (Estimated)
December 1, 2029
Study Completion (Estimated)
December 1, 2030
Last Updated
May 6, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- MGH - Contact the Partners Innovations team at http://www.partners.org/innovation
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.