Nirogacestat in Premenopausal Females With Desmoid Tumor/Aggressive Fibromatosis (DT/AF)

NCT07176689 | Recruiting Phase 4

• 2 other identifiers: NIR-DT-4012024-515215-21-00
• Study Type: interventional
• Target: 50
• Locations: 6 countries
• Sites: 23

Brief Summary

This study is being conducted to study how nirogacestat may affect the ovarian function of adult premenopausal women with progressing desmoid tumors/aggressive fibromatosis.

Conditions

Desmoid Tumor; Aggressive Fibromatosis

Keywords

Nirogacestat; PF-03084014; GSI; gamma secretase inhibitor; notch pathway; Ogsiveo

Outcome Measures

Primary Outcomes (1)

• Ovarian function recovery rate of ovarian toxicity (OT) treatment-emergent adverse events (TEAEs)

  Ovarian function recovery is defined as achieving the resumption of ≥2 consecutive menstrual periods and an FSH level \<30 mIU/mL with concomitant estradiol \<80 pg/mL OR resumption of ≥2 consecutive menstrual periods and AMH level within normal range adjusted for age and pretreatment baseline OR a positive serum β-HCG pregnancy test.

  Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period

Secondary Outcomes (3)

• Incidence of OT TEAEs

  Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period

• Time to ovarian function recovery in participants with a TEAE of OT

  Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period

• The incidence of adverse events (AEs) according to toxicities graded by National Cancer Institute (NCI) Common Technology Criteria for Adverse Events (CTCAE) Version 5

  Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period

Other Outcomes (10)

• Objective Response Rate (ORR)

  First day of every 3 cycles (each cycle is 28 days) for up to 24 cycles of treatment and up to 1 year in the Clinical Follow-up Period

• Duration of Response (DoR) for participants whose best response is CR or PR

  First day of every 3 cycles (each cycle is 28 days) until disease progression is observed or death, whichever comes first, up to 24 cycles of treatment and up to 1 year in the Clinical Follow-up Period

• Disease Control Rate (DCR) for participants whose best response is CR, PR or Stable Disease (SD)

  First day of every 3 cycles (each cycle is 28 days) for up to 24 cycles of treatment and up to 1 year in the Clinical Follow-up Period

Study Arms (1)

Nirogacestat

EXPERIMENTAL

Nirogacestat 150 mg by mouth, twice daily

Drug: Nirogacestat

Interventions

Nirogacestat DRUG

Nirogacestat oral tablet

Also known as: PF-03084014, Ogsiveo

Nirogacestat

Eligibility Criteria

• Age: 18 Years - 40 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participant is female, postpubertal aged ≥18 and ≤40 years of age at the time of signing the informed consent and premenopausal at baseline. Premenopausal is defined as meeting all of the following: Estradiol \>30 pg/mL. Follicle-stimulating hormone (FSH) \<40 IU/L. Regular menses (e.g., menstrual cycle length of 21 to 35 days) for at least 3 menstrual cycles prior to signing informed consent
• Participant uses 1 highly effective non-hormonal contraceptive method, has a negative pregnancy test prior to first dose of study treatment), is not breastfeeding, agrees to not harvest or donate eggs for at least 90 days prior to and during the study
• Participant has histologically confirmed DT/AF with symptomatic or progressive disease requiring systemic treatment
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 at screening
• Participant has adequate organ and bone marrow function.

You may not qualify if:

• Participant has known malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of nirogacestat
• Participant has experienced any of the following within 6 months of signing informed consent: clinically significant cardiac disease (New York Heart Association Class III or IV), myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
• Participant has had lymphoma, leukemia, or any malignancy within the past 5 years at the time of informed consent, except for any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast), with no evidence of metastatic disease for 3 years at the time of informed consent.
• Participant has known hepatic impairment
• Participant previously received or is currently receiving gamma secretase inhibitors or anti-Notch antibody therapy
• Participant is currently using any treatment for DT/AF including tyrosine kinase inhibitors (TKIs) or any investigational treatment 28 days (or 5 half-lives, whichever is longer) prior to the first dose of study treatment
• Participant is currently using or anticipates using food or drugs that are known strong/moderate cytochrome P450 (CYP) 3A4 inhibitors, or strong CYP3A inducers within 14 days prior to the first dose of study treatment.
• Participant has a history of polycystic ovary syndrome, hypothalamic amenorrhea, severe endometriosis involving ovaries, family history of primary ovarian insufficiency, any chromosomal abnormality, mutation, gene variant or medical condition associated with early/premature menopause, including a history of OT while on a TKI
• Participant is currently using or has used hormonal contraception or ovarian suppression within 90 days prior to first dose of study treatment
• Participant has a history of heavy tobacco smoking (≥20 pack years) or is a current smoker (\>1 pack per day)
• Participant has experienced other severe acute or chronic medical or psychiatric conditions within 1 year of signing informed consent.
• Participant is unable to comply with study related procedures (including, but not limited to, the completion of a menstrual diary and electronic patient-reported outcomes and ability to return to clinic for hormone level blood draws timed to the menstrual cycle (days 1-5)

Sponsors & Collaborators

• SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany: lead

Study Sites (23)

Cliniques Universitaires Saint-Luc (CUSL)

Brussels, 1200, Belgium

RECRUITING

Universitaetsmedizin Mannheim

Mannheim, 68167, Germany

RECRUITING

IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l.

Meldola, Forli-Cesena, 47014, Italy

RECRUITING

La Fondazione e l'Istituto di Candiolo

Candiolo, Torino, 10060, Italy

RECRUITING

IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola

Bologna, 40138, Italy

RECRUITING

IRCCS Istituto Ortopedico Rizzoli di Bologna

Bologna, 40138, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori Milano

Milan, 20133, Italy

RECRUITING

Istituto Nazionale Tumori I.R.C.C.S- Fondazione G. Pascale

Naples, 80131, Italy

RECRUITING

Policlinico Universitario Campus Bio-Medico

Roma, 00128, Italy

RECRUITING

Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL)

Amsterdam, 1066 CX, Netherlands

RECRUITING

Academisch Ziekenhuis Leiden

Leiden, 2333 ZA, Netherlands

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

RECRUITING

Institut Catala d'Oncologia

Barcelona, 08907, Spain

RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

RECRUITING

Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

RECRUITING

Cambridge University - Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

University College London Hospital

London, NW1 2PG, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Conditions

Desmoid Tumors

Interventions

nirogacestat

Condition Hierarchy (Ancestors)

Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Medical Responsible

  SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Central Study Contacts

US Medical Information

CONTACT

888-275-7376; eMediUSA@emdserono.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2025
• First Posted: September 16, 2025
• Study Start: September 17, 2025
• Primary Completion (Estimated): January 14, 2031
• Study Completion (Estimated): January 14, 2031
• Last Updated: July 17, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: IPD from completed trials will be publicly available within 6 months after all of the following events: * Approval of a product/new indication by major authorities (FDA, EMA, PMDA if requested) with no pending submissions * Public results via primary manuscript or trial registry disclosure * Legal authority to share data * Privacy protections are in place If approval is not sought or development is globally discontinued, data will be publicly available within 18 months after global trial completion. Further information on how to request data can be found on our website bit.ly/IPD21
• Access Criteria: Qualified researchers may propose access to IPD from sponsored trials via https://vivli.org/members/ourmembers/

Locations

BE (1); DE (1); NL (2); ES (8); GB (4); IT (7)