Actively Recruiting
A Single-Arm, Open-Label Phase 4 Study of Nirogacestat in Adult Premenopausal Females With Desmoid Tumors/Aggressive Fibromatosis
Led by SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany · Updated on 2026-05-08
50
Participants Needed
21
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
This research aims to study how nirogacestat may impact ovarian function in adult premenopausal women who have progressing desmoid tumors or aggressive fibromatosis. These rare, slow-growing soft tissue tumors are locally invasive and, despite being benign, can cause serious health problems. Nirogacestat is a tumor inhibitor approved in the USA for adults with progressing desmoid tumors needing systemic treatment, and this open-label Phase 4 study evaluates its effects on ovarian toxicity and overall safety in this population. Participants will receive nirogacestat tablets taken by mouth at a dose of 150 mg twice daily. The study includes up to 24 cycles of treatment, with each cycle lasting 28 days, followed by a clinical follow-up period of up to 2 years. During this time, researchers will assess ovarian function recovery, incidence of ovarian toxicity events, and other adverse effects related to the treatment. Throughout the study, participants will regularly provide hormone level blood samples timed to their menstrual cycle and complete menstrual diaries and electronic patient-reported outcome questionnaires. Researchers will monitor ovarian toxicity events and treatment safety using standardized criteria over the treatment and follow-up periods. The total involvement may last up to nearly three years, allowing detailed evaluation of ovarian function recovery and treatment tolerability.
CONDITIONS
Brief Title
Nirogacestat in Premenopausal Females With Desmoid Tumor/Aggressive Fibromatosis (DT/AF)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Female participants aged 18 to 40 years, postpubertal and premenopausal at baseline, with estradiol >30 pg/mL, FSH <40 IU/L, and regular menstrual cycles for at least 3 months
- Use of one highly effective non-hormonal contraceptive method
- Negative pregnancy test before first dose and not breastfeeding
- Agreement to not harvest or donate eggs for at least 90 days before and during the study
- Histologically confirmed desmoid tumor or aggressive fibromatosis with symptomatic or progressive disease requiring systemic treatment
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2 at screening
- Adequate organ and bone marrow function
You will not qualify if you...
- Known malabsorption syndrome or gastrointestinal conditions impairing nirogacestat absorption
- Clinically significant cardiac disease or events within 6 months prior to consent
- History of lymphoma, leukemia, or other malignancies within 5 years except certain treated localized cancers
- Known hepatic impairment
- Previous or current treatment with gamma secretase inhibitors or anti-Notch antibody therapy
- Use of tyrosine kinase inhibitors or investigational treatments for desmoid tumors within 28 days prior to first dose
- Use or planned use of strong/moderate CYP3A4 inhibitors or inducers within 14 days prior to first dose
- History of polycystic ovary syndrome, hypothalamic amenorrhea, severe ovarian endometriosis, primary ovarian insufficiency, or related genetic conditions
- Use of hormonal contraception or ovarian suppression within 90 days prior to first dose
- History of heavy tobacco smoking (≥20 pack years) or current smoking >1 pack/day
- Severe acute or chronic medical or psychiatric conditions within 1 year prior to consent
- Inability to comply with study procedures including menstrual diary and blood draws timed to menstrual cycle days 1-5
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 24 cycles (each cycle is 28 days)
Participants take Nirogacestat oral tablets twice daily to slow or stop tumor growth.
Visits occur regularly during treatment to monitor safety and effectiveness
Duration - Up to 2 years
Participants are monitored for up to 2 years after treatment to assess ovarian function recovery and long-term safety.
Follow-up visits occur periodically during this time
Trial Site Locations
Total: 21 locations
1
Cliniques Universitaires Saint-Luc (CUSL)
Brussels, Belgium, 1200
Actively Recruiting
2
Universitätsklinikum Mannheim, Mannheim Cancer Center
Mannheim, Germany, 68167
Actively Recruiting
3
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" IRCCS IRST. S.r.l.
Meldola, Forli-Cesena, Italy, 47104
Actively Recruiting
4
Fondazione del Piemonte per l'Oncologia Istituto di Candiolo IRCCS
Candiolo, Torino, Italy, 10060
Actively Recruiting
5
IRCCS Istituto Ortopedico Rizzoli
Bologna, Italy, 40136
Actively Recruiting
6
IRCCS Azienda Ospedaliero-Universitaria S. Orsola
Bologna, Italy, 40138
Actively Recruiting
7
Istituto Nazionale Tumori I.R.C.C.S- Fondazione G. Pascale
Naples, Italy, 80131
Actively Recruiting
8
Fondazione Policlinico Unversitario Campus Bio-Medico di Roma
Roma, Italy, 00128
Actively Recruiting
9
Nederlands Kanker Instituut - Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL)
Amsterdam, Netherlands, 1066 CX
Actively Recruiting
10
LUMC
Leiden, Netherlands, 2333 ZA
Actively Recruiting
11
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08041
Actively Recruiting
12
Hospital General Universitario Gregorio Maranon
Madrid, Spain, 28007
Actively Recruiting
13
Hospital Universitario Jimenez Diaz
Madrid, Spain, 28040
Actively Recruiting
14
Hospital General Universitario Gregorio Maranon
Madrid, Spain, 28041
Actively Recruiting
15
Hospital Universitario La Paz
Madrid, Spain, 28046
Actively Recruiting
16
Hospital Universitario y Politecnico La Fe
Valencia, Spain, 46026
Actively Recruiting
17
Hospital Universitario Miguel Servet
Zaragoza, Spain, 50009
Actively Recruiting
18
Cambridge University Hospitals NHS Foundation Trust
Cambridge, United Kingdom, CB2 0QQ
Actively Recruiting
19
University College London Hospitals NHS Foundation Trust
London, United Kingdom, NW1 2PG
Actively Recruiting
20
The Royal Marsden NHS Foundation Trust
London, United Kingdom, SW3 6JJ
Actively Recruiting
21
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Actively Recruiting
Research Team
U
US Medical Information
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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