What side effects are associated with this type of intervention?

Common treatments for Aggressive Fibromatosis include Gamma-Secretase Inhibitors like Nirogacestat, tyrosine kinase inhibitors (e.g., imatinib, nilotinib), and radiation therapy. Nirogacestat is currently under investigation, but similar agents may cause gastrointestinal issues, fatigue, and skin rashes. Tyrosine kinase inhibitors can lead to side effects such as edema, fatigue, and gastrointestinal disturbances. Radiation therapy, while effective, may result in long-term toxicities like joint stiffness, skin changes, and secondary malignancies.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved drugs for the treatment of Aggressive Fibromatosis (Desmoid Tumors) that function similarly to Nirogacestat, a Gamma-Secretase Inhibitor. Treatment options have generally included surgery, radiation therapy, and systemic therapies such as nonsteroidal anti-inflammatory drugs (NSAIDs), hormonal therapy, and chemotherapy. Nirogacestat represents a novel approach by targeting the Notch signaling pathway through gamma-secretase inhibition, which is currently under investigation.

What other types of research exist?

Promising novel alternatives to Nirogacestat for Aggressive Fibromatosis patients include: 1) Tyrosine kinase inhibitors (e.g., sorafenib, pazopanib) which have shown efficacy in clinical trials. 2) mTOR inhibitors (e.g., sirolimus) which have demonstrated potential in reducing tumor growth. 3) Beta-catenin inhibitors, which are being investigated for their role in targeting the Wnt signaling pathway involved in desmoid tumor pathogenesis.

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Gamma Secretase Inhibitor

Nirogacestat for Aggressive Fibromatosis (DeFi Trial)

Phase 3

Waitlist Available

Led By Bernd Kasper, MD

Research Sponsored by SpringWorks Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up daily for the last 7 days of every cycle (each cycle is 28 days) through study completion, an average of 2 years

Awards & highlights

Pivotal Trial

Summary

This trial tests nirogacestat, a medication that blocks a protein involved in tumor growth, on patients with desmoid tumors. These tumors are rare and can cause serious health issues. The drug aims to stop a chain reaction that helps these tumors grow. Nirogacestat has shown antitumor activity in several tumor types.

Who is the study for?

This trial is for adults with a type of tumor called desmoid tumor/aggressive fibromatosis (DT/AF) that has grown by at least 20% in the past year. Candidates must have finished any previous treatments for DT/AF at least 28 days before starting the study and resolved all treatment side effects to mild levels. They should be able to perform daily activities with slight limitations or better, as assessed by their ECOG performance status.

What is being tested?

The trial is testing nirogacestat, an oral tablet, against a placebo (a pill without active medication). Participants are randomly assigned to one of these two groups in a double-blind phase where neither they nor the researchers know who's receiving which treatment. After this phase, all participants will receive nirogacestat during an open-label phase.

What are the potential side effects?

While specific side effects for nirogacestat aren't listed here, common types of side effects from medications like it may include digestive issues, fatigue, skin reactions, changes in liver function tests and potentially increased risk of infections.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ daily for the last 7 days of every cycle (each cycle is 28 days) through study completion, an average of 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~daily for the last 7 days of every cycle (each cycle is 28 days) through study completion, an average of 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and daily for the last 7 days of every cycle (each cycle is 28 days) through study completion, an average of 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression Free Survival (PFS) Defined as the Time From Randomization Until Date of Assessment of Progression or Death by Any Cause.

Secondary study objectives

Change From Baseline at Cycle 10 in the Brief Pain Inventory (BPI) Average Pain Intensity (API) Score.

Change From Baseline at Cycle 10 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning

Change From Baseline at Cycle 10 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Role Functioning.

+4 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Open-Label Phase - NirogacestatExperimental Treatment1 Intervention

Nirogacestat 150 mg by mouth, twice daily

Group II: Double-Blind Phase - NirogacestatExperimental Treatment1 Intervention

Nirogacestat 150 mg by mouth, twice daily

Group III: Double-Blind Phase - PlaceboPlacebo Group1 Intervention

Placebo by mouth, twice daily

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Nirogacestat, a Gamma-Secretase Inhibitor, works by blocking the gamma-secretase enzyme, which plays a key role in the Notch signaling pathway involved in cell differentiation and proliferation. This inhibition can help reduce the growth and spread of aggressive fibromatosis tumors. For patients, this targeted approach offers a promising treatment option that may be more effective and have fewer side effects compared to traditional therapies.

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