Clinical trial NCT05130866: Efficacy and Safety of REC-2282 in Patients With Progressive Neurofibromatosis Type 2 (NF2) Mutated Meningiomas
Official title: A Two-staged, Phase 2/3, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of REC-2282 in Participants With Progressive NF2 Mutated Meningiomas
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Neurofibromatosis Type 2
Keywords: Neurofibromatosis Type 2; Neurofibromatosis Type II
Lead sponsor: Recursion Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2021-11-23
Enrollment: 92
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Two-staged, Phase 2/3, Randomized, Multicenter Efficacy and Safety Study.
Primary purpose: TREATMENT

Brief summary: This is a two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in patients with progressive NF2 mutated meningiomas.

Detailed description: This is a two-staged, Phase 2/3, randomized, multi-center study to investigate the efficacy and safety of REC-2282 in patients with progressive NF2 mutated meningiomas, with either NF2 disease-related meningioma or recurrent sporadic meningiomas that have NF2 mutations.

Cohort A will provide early data on efficacy and safety of REC-2282 in participants with progressive NF2 mutated meningiomas, and provide guidance for the dose in the confirmatory part of the study (Cohort B). The purpose of Cohort B of the study is to assess the efficacy and safety of REC-2282 compared with placebo in participants with progressive NF2 mutated meningiomas.

In both cohorts, there will be a screening period of up to 8 weeks, a treatment period, a 4-week safety follow-up period after the end of treatment, and a 6-month post-study follow-up. The first 8 participants enrolled in Cohort A will complete a food effect run-in sub study. At the end of the study period, participants may be offered participation in an open-label extension (OLE) period.

In Cohort A, adult participants will be randomized to one of two dose levels of REC-2282.

In Cohort B, participants will be randomized to REC-2282 treatment (dose to be determined from Cohort A) arm or placebo arm in a ratio of 2:1.

Eligibility criteria: Inclusion Criteria:

1. ≥12 years of age and weighing at least 40 kg
2. Progressive meningioma that is amenable to volumetric analysis
3. Has either 1) sporadic meningioma with confirmed NF2 mutation; or, 2) confirmed diagnosis of NF2 disease (revised Manchester criteria); or, 3) at least one NF2-related tumor (with pathogenic germline or proven mosaic NF2 variant)
4. Adequate bone marrow function
5. Has provided written informed consent/assent to participate in the study

Exclusion Criteria:

1. Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months.
2. Received prior surgery, radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor within 6 months prior to screening.
3. Received an anti- tumor agent for meningioma within 3 months, or 5 half-lives (whichever is longer), prior to screening.
4. History of an active malignancy within the previous 3 years except for localized cancers that are considered cured, and, in the opinion of the investigator, present a low risk of recurrence.
5. Received another investigational drug within 30 days prior to screening
6. Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dose of IMP.

Primary outcomes:
measure: Progression-free survival (PFS) in Cohort A
timeFrame: 6 months
measure: Progression-free survival (PFS) in Cohort B
timeFrame: Time from the date of randomization until disease progression or death from any cause, whichever occurs first, assessed up to 24 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: House Institute
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Overland Park
country: United States
facility: Sarah Cannon Cancer Institute - HCA Midwest
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota / Masonic Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
References: