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Compensation: Varies

Number of Visits: 28

Duration: Up to 2 years

35 Participants Needed

Nirogacestat for Desmoid Tumors

Recruiting at 100 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Oncology Group

Must not be taking: CYP3A4 inhibitors, NSAIDs

Disqualifiers: Active infection, Gastrointestinal conditions, Pregnancy, others

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

Prior Safety DataThis treatment has passed at least one previous human trial

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

Trial Summary

What is the purpose of this trial?

This trial studies how well nirogacestat works in children and adolescents with desmoid tumors that have not responded to other treatments and cannot be surgically removed. Nirogacestat is a medication taken by mouth that stops tumor growth by blocking necessary enzymes.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as strong inducers or inhibitors of CYP3A4, and NSAIDs for treating the tumor. You should discuss your current medications with the trial team to see if any need to be stopped or adjusted.

What data supports the effectiveness of the drug Nirogacestat for Desmoid Tumors?

Research shows that Nirogacestat, a gamma-secretase inhibitor, has been effective in treating desmoid tumors, with some patients experiencing partial or complete responses and stable disease. In a study with 17 patients, 29% had a partial response, and the drug was well tolerated, indicating promising results for this condition.¹ ² ³ ⁴ ⁵

Is Nirogacestat safe for humans?

Nirogacestat, also known as PF-03084014, has been generally well tolerated in studies with both adults and children with desmoid tumors. In one study, no severe side effects were reported in pediatric patients, and in another study with adults, it was well tolerated with participants experiencing improvements in symptoms.¹ ² ³ ⁶ ⁷

How is the drug Nirogacestat different from other treatments for desmoid tumors?

Nirogacestat is unique because it is a gamma-secretase inhibitor, which targets a specific pathway involved in the growth of desmoid tumors. Unlike other treatments, it has shown promising results in both adults and young patients, with a good safety profile and significant clinical benefits, such as partial and complete responses in some cases.¹ ² ³ ⁴ ⁸

Research Team

Fariba Navid

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for patients under 18 with aggressive desmoid tumors that can't be surgically removed and have grown despite previous treatment. Participants must not use NSAIDs for tumor treatment, avoid certain drugs affecting liver enzymes, and meet specific health criteria including organ function tests.

Inclusion Criteria

I haven't taken certain cancer drugs like sorafenib or tamoxifen in the last 28 days.

I can do most activities or at least move around in a wheelchair.

I haven't had chemotherapy in the last 2 weeks, or 4 weeks if it was nitrosourea.

See 27 more

Exclusion Criteria

I am currently breastfeeding.

I am using effective birth control and will continue for 6 months after my last dose.

Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study

See 11 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nirogacestat orally twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 2 years

Monthly visits for each 28-day cycle

Pharmacokinetics and Safety Monitoring

Pharmacokinetic parameters are assessed, and adverse events are monitored. Imaging and blood sample collection are conducted.

Up to Cycle 3 (each cycle lasts 28 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

30 days

Treatment Details

Interventions

Nirogacestat

Trial Overview The study is testing Nirogacestat's effectiveness on children with inoperable desmoid tumors. It involves monitoring the drug's impact through various assessments like echocardiography, MRI, CT scans, X-rays, biospecimen collection, questionnaires and quality-of-life evaluations.

Participant Groups

1Treatment groups

Experimental Treatment

Group I: Treatment (nirogacestat)Experimental Treatment8 Interventions

Patients receive nirogacestat PO BID on days 1-28. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO and CT or MRI on study. Patients may also undergo x-ray imaging and blood sample collection on study.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

SpringWorks Therapeutics, Inc.

Industry Sponsor

Trials

Recruited

900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]