Nirogacestat for Aggressive Fibromatosis

Overseen By Keila Torres, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antiretrovirals

Disqualifiers: Pregnancy, Breastfeeding, Cognitive impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

40 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial requires that participants stop their prior therapy for at least 28 days or 5 half-lives of the drug, whichever is longer, before starting the study treatment. However, the protocol does not specify if you need to stop all current medications, so it's best to discuss your specific situation with the study team.

How is the drug Nirogacestat different from other treatments for aggressive fibromatosis?

Nirogacestat is unique because it is a gamma-secretase inhibitor, which targets a specific pathway involved in tumor growth, and has shown promising results in treating desmoid tumors, a type of aggressive fibromatosis, especially in cases where traditional treatments like surgery and chemotherapy are not effective. ^{1 2 3 4 5}

Research Team

Keila Torres, MD, PHD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with desmoid tumors/aggressive fibromatosis who have either not been treated or whose tumors grew after treatment. They must be able to swallow tablets, sign consent, and have a tumor that can be measured. Participants need proper liver, kidney, and bone marrow function and agree to use contraception. Excluded are pregnant/breastfeeding women, those with certain health conditions or treatments that could interfere with the study.

Inclusion Criteria

My organs and bone marrow are working well.

I have a known heart condition or symptoms.

I can understand and am willing to sign the consent form.

Exclusion Criteria

Known hypersensitivity to nirogacestat or any of its excipients

Patients with psychiatric illness/social situations limiting compliance with study requirements

I cannot have repeated tissue samples taken.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nirogacestat by mouth every day of each 28-day study cycle

12 months

Monthly visits for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nirogacestat

Trial Overview The trial is testing nirogacestat's safety and effects on patients with desmoid tumors. About 40 participants will receive this investigational drug to see how well it works against their tumors which have shown growth despite previous treatments or in those untreated.

Participant Groups

Group I: nirogacestat Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

SpringWorks Therapeutics, Inc.

Industry Sponsor

Trials

14

Recruited

900+

Findings from Research

In a study of 90 children and adolescents with aggressive fibromatosis, systemic therapy (ST) was found to be effective, particularly when primary resection was not possible, leading to a 5-year overall survival rate of 100%.

The most common initial response to ST was stable disease at 3 months and partial response at 6 months, indicating that while ST can be beneficial, the 5-year event-free survival rate was only 44%, highlighting the need for ongoing treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy of aggressive fibromatosis in children and adolescents: Report of the Cooperative Weichteilsarkom Studiengruppe (CWS). Sparber-Sauer, M., Seitz, G., von Kalle, T., et al.[2019]

A three-year-old patient successfully underwent conservative surgery for aggressive fibromatosis of the mandible, remaining free of recurrence for nine years post-surgery.

The case suggests that conservative surgical approaches may be more beneficial than radical surgeries in children, as they minimize the impact on facial growth while effectively managing the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mandibular aggressive fibromatosis]. Jeblaoui, Y., Bouguila, J., Haddad, S., et al.[2007]

Wider surgical resection in patients with aggressive fibromatosis led to a lower recurrence rate, highlighting the importance of surgical intervention in managing this condition.

Two-thirds of the tumors exhibited estrogen or progesterone receptors, and all tumors showed inappropriate expression of c-sis and PDGF, suggesting these factors may play a significant role in the growth and behavior of aggressive fibromatosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aggressive fibromatosis. Alman, BA., Goldberg, MJ., Naber, SP., et al.[2004]

In a compassionate use study involving four pediatric and young adult patients with desmoid tumors, three patients showed durable benefits from the gamma-secretase inhibitor nirogacestat after a median treatment duration of 13.5 months, including one complete response and one partial response.

Importantly, nirogacestat was well-tolerated, with no patients experiencing severe adverse events (grade 3 or 4), suggesting a favorable safety profile for this treatment in young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of gamma-secretase inhibitor nirogacestat (PF-03084014) in desmoid tumor: Report of four pediatric/young adult cases. Takahashi, T., Prensner, JR., Robson, CD., et al.[2021]

In a study of 25 cases of aggressive fibromatosis in Iran, most patients were female and the tumors were primarily located in the abdominal area, lower extremities, and head and neck.

Surgical excision was performed in 23 cases, but 15 patients experienced at least one recurrence, highlighting the tumor's aggressive nature, although no deaths or metastasis were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aggressive Fibromatosis, Clinicopathologic Findings of 25 Cases; A Single-Center Experience and Review of the Literature. Geramizadeh, B., Jalali, F.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Systemic therapy of aggressive fibromatosis in children and adolescents: Report of the Cooperative Weichteilsarkom Studiengruppe (CWS). [2019]

2. France pubmed.ncbi.nlm.nih.gov

[Mandibular aggressive fibromatosis]. [2007]

3. United States pubmed.ncbi.nlm.nih.gov

Aggressive fibromatosis. [2004]

4. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of gamma-secretase inhibitor nirogacestat (PF-03084014) in desmoid tumor: Report of four pediatric/young adult cases. [2021]

5. Iran pubmed.ncbi.nlm.nih.gov

Aggressive Fibromatosis, Clinicopathologic Findings of 25 Cases; A Single-Center Experience and Review of the Literature. [2022]