Desmoid TumorPhase 4NCT07176689
Nirogacestat in Premenopausal Females With Desmoid Tumor/Aggressive Fibromatosis (DT/AF)
A Phase 4 study testing Nirogacestat in people with Desmoid Tumor and Aggressive Fibromatosis, run by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany at 23 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Desmoid Tumor, Aggressive Fibromatosis
- What is being tested?
- Nirogacestat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 23 sitesin 6 countries
- Study dates
- 17 Sep 2025to 26 Feb 2031
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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)
Trial locations and contacts
23 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
23 sites in 6 countries
Spain8 sites, 8 recruiting
- Recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Ana Sebio Garcia, MD, asebio@santpau.cat
- Recruiting
Institut Catala d'Oncologia
Barcelona, 08907
Laura Jimenez Colomo, ljcolomo@iconcologia.net
- Recruiting
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Rosa Alvarez, MD, rosa.alvarez.al@gmail.com
- Recruiting
Hospital Fundacion Jimenez Diaz
Madrid, 28040
Nadia Hindi Muniz, MD, nhindi@atbsarc.org
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
Aranzazu Manzano Fernández, MD, aranzazu.manzano@salud.madrid.org
- Recruiting
Hospital Universitario La Paz
Madrid, 28046
Andres Redondo Sanchez, MD, aredondo12@gmail.com
- Recruiting
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
Roberto Diaz, MD, diaz_rob@gva.es
- Recruiting
Hospital Universitario Miguel Servet
Zaragoza, 50009
Javier Martinez Trufero, MD, jmtrufero@seom.org
Italy7 sites, 7 recruiting
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant Orsola
Bologna, 40138
Maria Abbondanza Pantaleo, MD, maria.pantaleo@unibo.it
- Recruiting
IRCCS Istituto Ortopedico Rizzoli di Bologna
Bologna, 40138
Giorgio Frega, MD, giorgio.frega@ior.it
- Recruiting
La Fondazione e l'Istituto di Candiolo
Candiolo, Torino, 10060
Giovanni Grignani, MD, giovanni.grignani@ircc.it
- Recruiting
IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l.
Meldola, Forli-Cesena, 47014
Lorena Gurrieri, MD, Lorena.gurrieri@irst.emr.it
- Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori Milano
Milan, 20133
Silvia Stacchiotti, Silvia.Stacchiotti@istitutotumori.mi.it
- Recruiting
Istituto Nazionale Tumori I.R.C.C.S- Fondazione G. Pascale
Naples, 80131
Salvatore Tafuto, MD, s.tafuto@istitutotumori.na.it
- Recruiting
Policlinico Universitario Campus Bio-Medico
Roma, 00128
Bruno Vincenzi, MD, b.vincenzi@policlinicocampus.it
United Kingdom4 sites, 4 recruiting
- Recruiting
Cambridge University - Addenbrooke's Hospital
Cambridge, CB2 0QQ
Han Hsi Wong, MD, han.wong@nhs.net
- Recruiting
University College London Hospital
London, NW1 2PG
Vasilios Karavasilis, MD, vasilios.karavasilis@nhs.net
- Recruiting
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
Charlotte Benson, MD, charlotte.benson@rmh.nhs.uk
- Recruiting
The Christie NHS Foundation Trust
Manchester, M20 4BX
Alexander Lee, MD, alexander.lee1@nhs.net
Netherlands2 sites, 2 recruiting
- Recruiting
Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL)
Amsterdam, 1066 CX
Winette van der Graaf, MD, w.vd.graaf@nki.nl
- Recruiting
Academisch Ziekenhuis Leiden
Leiden, 2333 ZA
André Johan Gelderblom, MD, A.J.Gelderblom@lumc.nl
Belgium1 site, 1 recruiting
- Recruiting
Cliniques Universitaires Saint-Luc (CUSL)
Brussels, 1200
Filomena Mazzeo, MD, Filomena.mazzeo@saintluc.uclouvain.be
Germany1 site, 1 recruiting
- Recruiting
Universitaetsmedizin Mannheim
Mannheim, 68167
Bernd Kasper, MD, bernd.kasper@umm.de
About this study
Official title: A Single-Arm, Open-Label Phase 4 Study of Nirogacestat in Adult Premenopausal Females With Desmoid Tumors/Aggressive Fibromatosis (DT/AF)
This study is being conducted to study how nirogacestat may affect the ovarian function of adult premenopausal women with progressing desmoid tumors/aggressive fibromatosis.
Read the detailed description
Desmoid tumors, also referred to as aggressive fibromatosis, are rare, locally invasive, slow growing soft tissue tumors. Although considered benign because of their inability to metastasize, desmoid tumors can cause significant morbidity and occasionally mortality in patients.
Nirogacestat is a tumor inhibitor that works by slowing or stopping the growth of tumor cells. Nirogacestat is a tablet taken by mouth and has been approved in the USA for adult patients with progressing desmoid tumors who require systemic treatment.
This is an open-label study to characterize the incidence and ovarian function recovery rates of ovarian toxicity (OT) events and to evaluate the efficacy, safety, and tolerability of nirogacestat in postpubertal and premenopausal females with desmoid tumors (DT).
- Conditions
- Desmoid Tumor, Aggressive Fibromatosis
- Being tested
- Nirogacestat
- Keywords
- Nirogacestat, PF-03084014, GSI, gamma secretase inhibitor, notch pathway, Ogsiveo
- Medical subject headings
- Desmoid Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NirogacestatDrug
Also called PF-03084014, Ogsiveo
Nirogacestat oral tablet
| Study group | Role | What they receive |
|---|---|---|
| Nirogacestat | Experimental | Nirogacestat 150 mg by mouth, twice daily Receives: Drug: Nirogacestat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
OT is any new onset amenorrhea lasting ≥3 consecutive menstrual periods, FSH level ≥30 mIU/mL and a negative β-HCG pregnancy test.
Measured: 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
Time to ovarian function recovery is evaluated in participants who had a TEAE of OT and is defined as the time it takes to resolve.
Measured: 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
Measured: Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2025
- Study start17 Sep 2025
- Primary completion26 Feb 2031 (estimated)
- Study completion26 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Desmoid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07176689
- Sponsor's protocol ID
- NIR-DT-401
- Other IDs
- 2024-515215-21-00
- Status last verified
- Oct 2026
- First submitted
- 31 Jul 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD supporting publicly available results will be evaluated for sharing.
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Arm, Open-Label Phase 4 Study of Nirogacestat in Adult Premenopausal Females With Desmoid Tumors/Aggressive Fibromatosis (DT/AF)
- ClinicalTrials.gov ID
- NCT07176689
- Acronym / sponsor ID
- NIR-DT-401
- Conditions
- Desmoid Tumor, Aggressive Fibromatosis
- Keywords
- Nirogacestat, PF-03084014, GSI, gamma secretase inhibitor, notch pathway, Ogsiveo
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 17 Sep 2025 (actual)
- Primary completion
- 26 Feb 2031 (estimated)
- Study completion
- 26 Feb 2031 (estimated)
- First posted
- 16 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being conducted to study how nirogacestat may affect the ovarian function of adult premenopausal women with progressing desmoid tumors/aggressive fibromatosis.
Detailed description
Desmoid tumors, also referred to as aggressive fibromatosis, are rare, locally invasive, slow growing soft tissue tumors. Although considered benign because of their inability to metastasize, desmoid tumors can cause significant morbidity and occasionally mortality in patients.
Nirogacestat is a tumor inhibitor that works by slowing or stopping the growth of tumor cells. Nirogacestat is a tablet taken by mouth and has been approved in the USA for adult patients with progressing desmoid tumors who require systemic treatment.
This is an open-label study to characterize the incidence and ovarian function recovery rates of ovarian toxicity (OT) events and to evaluate the efficacy, safety, and tolerability of nirogacestat in postpubertal and premenopausal females with desmoid tumors (DT).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nirogacestat | Experimental | Drug: NirogacestatNirogacestat 150 mg by mouth, twice daily |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NirogacestatAlso: PF-03084014, OgsiveoNirogacestat oral tablet | Drug | Nirogacestat |
Primary outcome
Ovarian function recovery rate of ovarian toxicity (OT) treatment-emergent adverse events (TEAEs)
Time frame: Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period
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.
3 secondary outcomes
Incidence of OT TEAEs
Time frame: 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
Time frame: 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
Time frame: Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- Medical Information Location Map - Med Info ContactsLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. IPD supporting publicly available results will be evaluated for sharing.
Related trials for Desmoid Tumor
RecruitingPhase 2
A Study in Adults With Desmoid Tumors
Desmoid Tumor
RecruitingPhase 1/2
FOG-001 in Locally Advanced or Metastatic Solid Tumors
Cancer, Colorectal Cancer
Active, not recruitingPhase 2
A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery
Desmoid Fibromatosis, Recurrent Desmoid Fibromatosis
Enrolling by invitationObservational study
Patient-reported Outcomes Following Percutaneous Ablation of Desmoid Tumors
Desmoid Tumor, Aggressive Fibromatoses
Active, not recruitingPhase 2
A Study of Nirogacestat in Japanese Adults With Desmoid Tumors/Aggressive Fibromatosis (DT/AF)
Desmoid Tumor, Aggressive Fibromatosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Medical Responsible study director
SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany
23 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nirogacestat in people with Desmoid Tumor and Aggressive Fibromatosis, run by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany at 23 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Spain, Italy, United Kingdom, Netherlands, Belgium and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact US Medical Information (888-275-7376, eMediUSA@emdserono.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ovarian function recovery rate of ovarian toxicity (OT) treatment-emergent adverse events (TEAEs) (time frame: Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.