Innovative Trial for Understanding the Impact of Targeted Therapies in NF2 (INTUITT-NF2)
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|ClinicalTrials.gov Identifier: NCT04374305|
Recruitment Status : Recruiting
First Posted : May 5, 2020
Last Update Posted : November 17, 2020
This is a multi-arm phase II platform-basket screening study designed to test multiple experimental therapies simultaneously in patients with neurofibromatosis type 2 (NF2) 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 to receive new drugs throughout this study. Embedded within the Master Study are individual drug substudies.
- Investigational Drug Sub-study A: Brigatinib
|Condition or disease||Intervention/treatment||Phase|
|Neurofibromatosis Type 2 Vestibular Schwannoma Non-vestibular Schwannoma Meningioma Ependymoma||Drug: Brigatinib||Phase 2|
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.
The Master study is intended to enroll participants who will be placed into different treatment arms (sub-studies) which will each have an additional consent and enrollment processes.
-- 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.
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.
- It is expected that 40 people will take part in the Brigatinib Sub-study.
- The sub-study with brigatinib will include 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.
|Study Type :||Interventional|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||The study is a platform trial that includes a Master Protocol with embedded Drug Sub-studies. Initially, there is 1 drug substudy of brigatinib. The overall number of arms is not fixed by design because the investigators include arm-dropping rules for futility and allow for the possibility of arm addition by amendment.|
|Masking:||None (Open Label)|
|Official Title:||Innovative Trial for Understanding the Impact of Targeted Therapies in NF2 (INTUITT-NF2)|
|Actual Study Start Date :||June 20, 2020|
|Estimated Primary Completion Date :||December 1, 2029|
|Estimated Study Completion Date :||December 1, 2030|
Experimental: Brigatinib Sub-Study
Subjects 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.
Oral daily per predetermined dosage per protocol.
Other Name: Alunbrig
- Radiographic response rate (for each drug substudy) [ Time Frame: 2 years ]
Radiographic response rates in target tumors according to tumor-associated criteria:
- VS, non-VS, and meningiomas: Dombi criteria (2013)
- Ependymomas: RECIST 1.12
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability [ Time Frame: 2 years ]Number of Participants with Treatment Emergent Adverse Events as Assessed CTCAE v5.0
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04374305
|Contact: Scott Plotkin, MDemail@example.com|
|United States, Massachusetts|
|Dana Farber Cancer Institute||Not yet recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Nicole Ullrich, MD 617-355-2751|
|Principal Investigator: Nicole Ullrich, MD|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Scott Plotkin, MD 617-724-8770 firstname.lastname@example.org|
|Principal Investigator: Scott Plokin, MD|
|United States, New York|
|New York University Langone Medical Center||Recruiting|
|New York, New York, United States, 10016|
|Contact: Jeffrey Allen, MD Jeffrey.Allen@nyulangone.org|
|Principal Investigator: Jeffrey Allen, MD|
|Principal Investigator:||Scott Plotkin, MD||Massachusetts General Hospital|