Evaluation of the Response and Non-response of Nirogacestat in Desmoid Tumors- Clinical Study

NCT05879146 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2022-0610NCI-2023-04177
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

To learn about the safety and effects of an investigational drug called nirogacestat when given to participants with a desmoid tumor/aggressive fibromatosis

Conditions

Tumor

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year.

Study Arms (1)

nirogacestat

EXPERIMENTAL

Participants will take nirogacestat by mouth every day of each 28-day study cycle. Based on when you enroll in this study, you will take nirogacestat either 1 time a day at about the same time each day OR 2 times a day, about 12 hours apart.

Drug: Nirogacestat

Interventions

Nirogacestat DRUG

Given by PO

nirogacestat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• This study will enroll approximately 40 participants diagnosed with DT. Participants must meet the following eligibility criteria to be enrolled:
• Age ≥ 18 years. Individuals younger than 18 years old are excluded. More than 99% of the population evaluated at MDACC with a diagnosis of DT is older than 18. Sixty-three percent of the population with a diagnosis of DT evaluated at MDACC are 10 - 54 years old. The remaining 37 percent are older than 54 years old. Additionally, most of the robust data related to dosing or adverse event data currently available on the use of nirogacestat is in adults
• Histologically documented DT with evidence of radiographic tumor progression (≥ 10% or absolute increase in dimensions of ≥ 10 mm in maximal diameter) in unidimensional measurement within the previous 18 months. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam
• Recurrent or primary disease
• Symptomatic disease or impending morbidity (as defined by physician) and patient and physician agree treatment would be of benefit
• Treatment naïve or progression on or after any prior therapy for DT. Participant must have discontinued prior therapy for at least 28 days or 5 half-lives of the drug, whichever is greater. All toxicities from prior therapy must be resolved to Grade ≤ 1 or clinical baseline. There is no limit on the number of previous systemic treatments received
• Able to tolerate radiographic progression (up to 20% increase in tumor longest diameter) as determined by treating oncologist based on morbidity and tumor growth is not threatening vital structures
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Are appropriate for systemic therapy
• Have accessible tumors for serial biopsies
• Agree to provide new tumor tissue. Tumor tissue from the archival (tumor bank) may be used if the biopsy is performed after discontinuation of prior therapy and the participant must have discontinued prior therapy for at least 28 days or five half-lives of the drug, whichever is greater
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Adequate organ and bone marrow function as defined by the following screening laboratory values:
• Absolute neutrophil count ≥ 1500 cells/μL;

You may not qualify if:

• Participants are excluded from this study if any of the following criteria apply:
• Unable to undergo serial biopsies
• Participants with familial adenomatous polyposis
• Unable to tolerate MRI or for whom MRI is contraindicated
• Pregnant or breastfeeding women are excluded from this study. Based on findings in animal studies, oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than adult human exposures at the recommended dose of 150 mg twice daily. Nirogacestat should be avoided during pregnancy
• There is no data regarding the presence of nirogacestat or its metabolites in either human or animal milk or its effects on a breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child from nirogacestat, advise women not to breastfeed during treatment with nirogacestat.
• Known hypersensitivity to nirogacestat or any of its excipients
• Participants requiring the use of any excluded concomitant medications listed in Table 2 during the course of the study
• Unable to comply with study-related procedures in the opinion of the investigator
• Patients with cognitive impairment requiring a legally authorized representative for consent
• Patients with uncontrolled intercurrent illness (Indicate clearly what type or extent)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with positive viral load will be excluded
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia
• Patients who are receiving any other investigational agents

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• SpringWorks Therapeutics, Inc.: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Neoplasms

Interventions

nirogacestat

Study Officials

• Keila Torres, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Keila Torres, MD,PHD

CONTACT

(713) 792-4242; ketorres@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2023
• First Posted: May 30, 2023
• Study Start: November 26, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (1)