Brigatinib in NF2-Related Schwannomatosis with Progressive Tumors.
Scott R Plotkin, Kaleb H Yohay, Phioanh L Nghiemphu...
https://pubmed.ncbi.nlm.nih.gov/38904277Actively Recruiting
Phase 2
Age: 12Years +
All Genders
ID04374305
Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
Led by Scott R. Plotkin, MD, PhD · Updated on 2026-05-06
109
Participants Needed
6
Research Sites
52 weeks
Total Duration
On this page
Sponsors
S
Scott R. Plotkin, MD, PhD
Lead Sponsor
T
Takeda
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are conducting a phase II basket trial to study multiple experimental treatments in patients with NF2-related schwannomatosis (NF2-SWN) who have progressive tumors including vestibular schwannomas, non-vestibular schwannomas, meningiomas, and ependymomas. This trial allows people with various NF2-SWN tumor types to receive new drugs through individual drug substudies within the Master Study framework. The goal is to assess the activity and safety of these therapies over time. The study includes three investigational drug sub-studies: Brigatinib, Neratinib, and a combination of Retifanlimab plus Bevacizumab. Each drug has specific dosing schedules: Brigatinib is taken orally daily with dose escalation if tolerated; Neratinib is taken orally daily with initial lower dosing for tolerability; Retifanlimab and Bevacizumab are administered by intravenous infusion every three weeks over a year-long treatment period. Participants may be randomized to one of these treatment arms or remain under observation if ineligible for active treatment arms. The study allows switching between sub-studies if tumors grow during treatment. Participants undergo screening for eligibility, randomization, and treatment or observation for up to 10 years. Researchers will monitor tumor responses using radiographic imaging to measure changes in tumor size as the primary outcome over two years. Safety and tolerability are also tracked by recording adverse events. Additional assessments may include PET scans for a subset of participants in the Neratinib sub-study. Participants will have regular visits for treatment administration, imaging, lab tests, and questionnaires to assess treatment effects and side effects throughout the study duration.
CONDITIONS
Brief Title
Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
Who Can Participate
Age: 12Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Patients must have a pathogenic NF2 gene variant or meet NIH or Manchester criteria for NF2 diagnosis.
- Must have NF2-related tumors (vestibular schwannomas, non-vestibular schwannomas, meningiomas, or ependymomas) showing radiographic progression within the past 36 months.
- Must have measurable disease as defined by MRI or linear measurement criteria.
- Tumors must not be suitable for surgery due to refusal or high surgical risk.
- Age 12 years or older at treatment start.
- Life expectancy greater than 1 year with Karnofsky performance status ≥70 or ECOG 0 or 1.
- Ability to understand and provide informed consent and assent.
- Established relationship with a primary care physician.
You will not qualify if you...
- Chemotherapy within 4 weeks prior to study registration or unresolved toxicities.
- Radiation to target tumor within 3 years before registration.
- Receiving other investigational agents.
- Tumors likely to require surgery or active treatment within 6 months.
- History of other malignancies unless disease-free for at least 2 years and low risk for recurrence.
- Uncontrolled illnesses including infections, heart failure, unstable angina, arrhythmia, or psychiatric conditions limiting compliance.
- Pregnant or breastfeeding women.
- Specific exclusions for sub-studies including recent major surgery, cardiovascular disease, or inability to swallow pills (for oral drugs).
- Use of certain medications or conditions that may interfere with study drugs or safety.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Up to 48 weeks for retifanlimab plus bevacizumab; duration varies for brigatinib and neratinib sub-studies
Participants receive one of the experimental treatments: brigatinib, neratinib, or retifanlimab plus bevacizumab, depending on their assigned sub-study. Treatment duration and schedule vary by sub-study.
Daily oral dosing for brigatinib and neratinib; IV infusions every 3 weeks for retifanlimab plus bevacizumab; treatment cycles last 42 days for retifanlimab plus bevacizumab
Follow-up
Duration - Up to 10 years
Participants are observed after treatment completion to monitor safety, effectiveness, and tumor progression, including long-term observation up to 10 years for those remaining on the Master Study.
Periodic visits for follow-up assessments; specific frequency varies
Trial Site Locations
Total: 6 locations
1
UCLA Medical Center
Los Angeles, California, United States, 90095
Actively Recruiting
2
University of Miami
Miami, Florida, United States, 33136
Actively Recruiting
3
Indiana University School of Medicine
Indianopolis, Indiana, United States, 46202
Not Yet Recruiting
4
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
Actively Recruiting
5
Massachusetts General Hospital
Boston, Massachusetts, United States, 02115
Actively Recruiting
6
New York University Langone Medical Center
New York, New York, United States, 10016
Actively Recruiting
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Research Team
S
Scott Plotkin, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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