Nirogacestat for Desmoid Tumors

Not currently recruiting at 107 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 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: 28

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects and safety of a drug called nirogacestat (also known as PF-03084014 or PF-3084014) for children and teens with desmoid tumors, a non-cancerous growth that can still cause problems. The focus is on patients whose tumors have grown after other treatments and cannot be surgically removed. The trial seeks participants under 18 who have undergone at least one unsuccessful treatment for their tumor. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that nirogacestat is likely to be safe for humans?

Research shows that nirogacestat is generally safe for treating desmoid tumors. Studies consistently find that most side effects are mild or moderate, such as fatigue or nausea, while serious side effects are rare. Over time, people taking nirogacestat usually tolerate it well, allowing them to continue treatment without major issues.

Earlier research indicated that nirogacestat has a manageable safety profile. While side effects exist, they do not outweigh the benefits. The treatment also showed promise in shrinking tumors, which is encouraging. These findings support the idea that nirogacestat is a safe option for those considering this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nirogacestat is unique because it targets desmoid tumors by inhibiting gamma-secretase, an enzyme involved in the growth of these tumors. Unlike traditional treatments like surgery, radiation, or NSAIDs, which can have varied success and significant side effects, nirogacestat offers a targeted approach that specifically disrupts tumor growth pathways. Researchers are excited about this treatment due to its potential to manage tumors more effectively with less toxicity, providing a promising alternative for patients who have limited options.

What evidence suggests that nirogacestat might be an effective treatment for desmoid tumors?

Research has shown that nirogacestat, the treatment under study in this trial, holds promise for treating desmoid tumors. Studies have found that it can shrink tumors and provide lasting relief from symptoms like pain. In one study, patients experienced about 15.9 months without tumor growth. Long-term use of nirogacestat also led to further tumor shrinkage and lasting benefits. Additionally, patients reported significant relief from symptoms, suggesting it could effectively manage desmoid tumors. ^{1 2 3 4 5}

Who Is on the Research Team?

Fariba Navid

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Treatment (nirogacestat) Experimental Treatment 8 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.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

SpringWorks Therapeutics, Inc.

Industry Sponsor

Trials

14

Recruited

900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2210140

Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors Results · Efficacy. As of the data-cutoff date (April 7, 2022), the overall median follow-up for progression-free survival was 15.9 months.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00582

Efficacy and Safety of Long-Term Continuous Nirogacestat ... In conclusion, long-term continuous nirogacestat treatment was associated with further tumor size reductions, durable objective responses, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03785964

Nirogacestat for Adults With Desmoid Tumor/Aggressive ... This study evaluates nirogacestat (PF-03084014) in the treatment of desmoid tumor/aggressive fibromatosis (DT/AF).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11815814/

Nirogacestat—the pathway to approval of the first treatment ... Beyond reductions in tumor size, this trial noted that every patient had “dramatic, sustained symptomatic relief (decreased tumor pain and/or ...

5. ir.springworkstx.com ir.springworkstx.com/news-releases/news-release-details/springworks-therapeutics-announces-long-term-efficacy-and-safety/

Press Release Details Efficacy of nirogacestat in patients with poor prognostic factors for desmoid tumors: patient-reported outcomes, progression-free survival ...