Clinical trial • Phase IV • Oncology|Rare Disease
NIROGACESTAT HYDROBROMIDE for Desmoid tumour (Aggressive fibromatosis)
Phase IV trial of NIROGACESTAT HYDROBROMIDE for Desmoid tumour (Aggressive fibromatosis). open-label, none/not specified-controlled. 47 participants.
Overview
- Trial Therapeutic Area
- Oncology|Rare Disease
- Trial Disease
- Desmoid tumour (Aggressive fibromatosis)
- Trial Stage
- Phase IV
- Drug Modality
- Small molecule
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 05-06-2025
- First CTIS Authorization Date
- 15-09-2025
Trial design
open-label, none/not specified-controlled Phase IV trial in Germany, Spain, Italy and others.
- Open Label
- Yes
- Comparator
- None/Not specified
- Target Sample Size
- 47
Eligibility
Recruits 47 Vulnerable population flag selected. Study enrols adult postpubertal premenopausal females only; inclusion criterion 8 requires participants to be "Capable of giving signed informed consent." Consent is provided by the participant (no minor assent procedures described). Language-specific ICFs and pregnancy-specific ICFs are provided in the trial documents..
- Pregnancy Exclusion
- 2.Participant is eligible to participate if she is not pregnant or breastfeeding, and the following conditions apply: - Is of childbearing potential but is abstinent or using at least 1 highly effective contraceptive method. - The participant has not harvested or donated eggs for the purpose of reproduction for at least 90 days prior to the first dose of nirogacestat and agrees to not harvest or donate eggs for the purpose of reproduction during the Treatment and Clinical Follow-up Periods.
- Vulnerable Population
- Vulnerable population flag selected. Study enrols adult postpubertal premenopausal females only; inclusion criterion 8 requires participants to be "Capable of giving signed informed consent." Consent is provided by the participant (no minor assent procedures described). Language-specific ICFs and pregnancy-specific ICFs are provided in the trial documents.
Inclusion criteria
- {"criterion_text":"- 1.Participant must be female, postpubertal aged ≥18 and ≤40 years of age at the time of signing the informed consent and premenopausal at baseline.\n- 2.Participant is eligible to participate if she is not pregnant or breastfeeding, and the following conditions apply: - Is of childbearing potential but is abstinent or using at least 1 highly effective contraceptive method. - The participant has not harvested or donated eggs for the purpose of reproduction for at least 90 days prior to the first dose of nirogacestat and agrees to not harvest or donate eggs for the purpose of reproduction during the Treatment and Clinical Follow-up Periods.\n- 3.Participant has histologically confirmed DT/AF with symptomatic or progressive disease requiring systemic treatment.\n- 4.Participants who have received prior chemotherapy or radiation must meet the definition of premenopausal ≥2 weeks after the end of the final cycle of chemotherapy or final radiation treatment. Participants who have received prior gonadotoxic chemotherapy or pelvic radiotherapy are not eligible for this study.\n- 5.Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 at screening.\n- 6.Participant has adequate organ and bone marrow function.\n- 7.Participant can swallow tablets and has no gastrointestinal conditions affecting absorption.\n- 8.Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol."}
Exclusion criteria
- {"criterion_text":"- 1.Participant has known malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of nirogacestat.\n- 10.Participant is currently enrolled or was enrolled within 28 days of first dose of study treatment in another clinical study with any investigational drug or device. Participationin observational studies may be permitted with prior approval from the medical monitor/sponsor.\n- 11.Participant has a history of heavy tobacco smoking (defined as ≥20 pack years) and/or is a current smoker (>1 pack per day) at the time of informed consent.\n- 12.Participant has experienced other severe acute or chronic medical or psychiatric conditions, including recent or active suicidal ideation or behavior, or a laboratory abnormality that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.\n- 13.Participant has known hypersensitivity to the active substance or to any of the excipients of nirogacestat.\n- 14.Participant is unable to comply with study-related procedures including, but not limited to the following: the completion of a menstrual diary and electronic patient-reported outcomes and the ability to return to the clinic for hormone level blood draws timed to the menstrual cycle (Day 1-5) at the required visits.\n- 2.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 -Symptomatic pulmonary embolism\n- 3.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 with no evidence of metastatic disease for 3 years at the time of informed consent.\n- 4.Participant has known severe hepatic impairment.\n- 5.Participant previously received or is currently receiving therapy with gamma secretase (GS) inhibitors or anti-Notch antibody therapy.\n- 6.Participant is currently using any treatment for DT/AF including tyrosine kinase inhibitors (TKIs) or any investigational treatment within 28 days (or 5 half-lives, whichever is longer) prior to the first dose of study treatment. All toxicities from prior therapy must be resolved to Grade ≤1 or clinical baseline prior to the first dose of study treatment.\n- 7.Participant is currently using or anticipates using food or drugs that are known strong or moderate cytochrome P450 (CYP) 3A4 inhibitors or strong or moderate CYP3A inducers within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study treatment.\n- 8.Participants 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.\n- 9.Participant is currently using or has used hormonal contraception or ovarian suppression within 90 days prior to the first dose of study treatment."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Ovarian function recovery rate of OT TEAEs. Ovarian function recovery is defined as achieving the resumption of ≥2 consecutive menstrual periods and an follicle stimulating hormone (FSH) level <30 mIU/mL with concomitant estradiol <80 pg/mL, OR resumption of ≥2 consecutive menstrual periods and anti-mullerian hormone (AMH) level within normal range adjusted for age and pretreatment baseline, OR a positive serum beta-human chorionic gonadotropin (β-HCG) pregnancy test.","definition_or_measurement_approach":"Ovarian function recovery defined as: resumption of ≥2 consecutive menstrual periods AND (FSH <30 mIU/mL with estradiol <80 pg/mL) OR (resumption of ≥2 consecutive menstrual periods AND AMH within age-adjusted normal range and pretreatment baseline) OR positive serum β-HCG pregnancy test. Measurement via menstrual history and laboratory hormone tests (FSH, estradiol, AMH, β-HCG)."}
Secondary endpoints
- {"endpoint_text":"- 1.Incidence of OT TEAEs. OT is defined as new onset amenorrhea lasting ≥3 consecutive menstrual periods, FSH level ≥30 mIU/mL, AND a negative β-HCG pregnancy test.","definition_or_measurement_approach":"Incidence measured by clinical assessment of menstruation, FSH laboratory levels (≥30 mIU/mL) and negative β-HCG pregnancy test."}
- {"endpoint_text":"- 2.Time to ovarian function recovery in participants with a TEAE of OT.","definition_or_measurement_approach":"Time-to-event measured from onset of OT TEAE to meeting ovarian function recovery criteria (as per primary endpoint definitions)."}
- {"endpoint_text":"- 3.Safety endpoints will include incidence of TEAEs, changes in laboratory parameters including hormones, vital signs, and physical examination findings. Tolerability will be assessed according to toxicities graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.","definition_or_measurement_approach":"Safety assessed by recording TEAEs, laboratory tests including hormone panels, vital signs, physical exams; grading per NCI CTCAE v5.0."}
Recruitment
- Planned Sample Size
- 47
- Recruitment Window Months
- 36
- Consent Approach
- Informed consent must be signed by the participant (inclusion criterion 8: 'Capable of giving signed informed consent'). Participant-facing information and ICF documents are provided (multiple language versions present in the dossier: English, Spanish, Italian, Dutch, German and French variants are included among submitted SIS/ICF and patient-facing documents). Pregnancy-specific ICFs and addenda are available. No assent process for minors is described (study enrols adults ≥18).
Geography
- Total Number Of Sites
- 20
- Total Number Of Participants
- 47
Germany
- Earliest CTIS Part Ii Submission Date
- 19-08-2025
- Latest Decision Or Authorization Date
- 19-02-2026
- Processing Time Days
- 184
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- Heidelberg University
- Department Name
- Interdisciplinary Tumor Center, Universitätsklinikum Mannheim (UMM)
- Principal Investigator Name
- Bernd Kasper
- Principal Investigator Email
- bernd.kasper@umm.de
- Contact Person Name
- Bernd Kasper
- Contact Person Email
- bernd.kasper@umm.de
Spain
- Earliest CTIS Part Ii Submission Date
- 17-09-2025
- Latest Decision Or Authorization Date
- 20-02-2026
- Processing Time Days
- 156
- Number Of Sites
- 8
- Number Of Participants
- 22
Sites
- Site Name
- Hospital Universitario La Paz
- Department Name
- Oncology
- Principal Investigator Name
- Andres Redondo Sanchez
- Principal Investigator Email
- aredondo12@gmail.com
- Contact Person Name
- Andres Redondo Sanchez
- Contact Person Email
- aredondo12@gmail.com
- Site Name
- Institut Catala D'oncologia
- Department Name
- Oncology
- Principal Investigator Name
- Laura Jimenez Colomo
- Principal Investigator Email
- ljcolomo@iconcologia.net
- Contact Person Name
- Laura Jimenez Colomo
- Contact Person Email
- ljcolomo@iconcologia.net
- Site Name
- Hospital Universitario Fundacion Jimenez Diaz
- Department Name
- Oncology
- Principal Investigator Name
- Nadia Hindi Muniz
- Principal Investigator Email
- nhindi@atbsarc.org
- Contact Person Name
- Nadia Hindi Muniz
- Contact Person Email
- nhindi@atbsarc.org
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- Oncology
- Principal Investigator Name
- Rosa Alvarez
- Principal Investigator Email
- rosa.alvarez.al@gmail.com
- Contact Person Name
- Rosa Alvarez
- Contact Person Email
- rosa.alvarez.al@gmail.com
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Department Name
- Oncology
- Principal Investigator Name
- Roberto Diaz Beveridge
- Principal Investigator Email
- diaz_rob@gva.es
- Contact Person Name
- Roberto Diaz Beveridge
- Contact Person Email
- diaz_rob@gva.es
- Site Name
- Hospital De La Santa Creu I Sant Pau
- Department Name
- Oncology
- Principal Investigator Name
- Ana Sebio Garcia
- Principal Investigator Email
- asebio@santpau.cat
- Contact Person Name
- Ana Sebio Garcia
- Contact Person Email
- asebio@santpau.cat
- Site Name
- Hospital Universitario Miguel Servet
- Department Name
- Oncology
- Principal Investigator Name
- Javier Martinez Trufero
- Principal Investigator Email
- jmtrufero@seom.org
- Contact Person Name
- Javier Martinez Trufero
- Contact Person Email
- jmtrufero@seom.org
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Oncology
- Principal Investigator Name
- Aranzazu Manzano Fernández
- Principal Investigator Email
- aranzazu.manzano@salud.madrid.org
- Contact Person Name
- Aranzazu Manzano Fernández
- Contact Person Email
- aranzazu.manzano@salud.madrid.org
Italy
- Earliest CTIS Part Ii Submission Date
- 28-08-2025
- Latest Decision Or Authorization Date
- 25-03-2026
- Processing Time Days
- 209
- Number Of Sites
- 7
- Number Of Participants
- 10
Sites
- Site Name
- Fondazione Policlinico Universitario Campus Bio-medico In Forma A Bbreviata Fon
- Department Name
- Medical Oncology
- Principal Investigator Name
- Bruno Vincenzi
- Principal Investigator Email
- b.vincenzi@policlinicocampus.it
- Contact Person Name
- Bruno Vincenzi
- Contact Person Email
- b.vincenzi@policlinicocampus.it
- Site Name
- Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
- Department Name
- Medical Oncology
- Principal Investigator Name
- Loredana Gurrieri
- Principal Investigator Email
- lorena.gurrieri@irst.emr.it
- Contact Person Name
- Loredana Gurrieri
- Contact Person Email
- lorena.gurrieri@irst.emr.it
- Site Name
- Istituto Ortopedico Rizzoli
- Department Name
- Medical Oncology
- Principal Investigator Name
- Giorgio Frega
- Principal Investigator Email
- giorgio.frega@ior.it
- Contact Person Name
- Giorgio Frega
- Contact Person Email
- giorgio.frega@ior.it
- Site Name
- Istituto Di Candiolo Fondazione Del Piemonte Per L'Oncologia IRCCS
- Department Name
- Medical Oncology
- Principal Investigator Name
- Giovanni Grignani
- Principal Investigator Email
- giovanni.grignani@ircc.it
- Contact Person Name
- Giovanni Grignani
- Contact Person Email
- giovanni.grignani@ircc.it
- Site Name
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
- Department Name
- Medical Oncology
- Principal Investigator Name
- Maria Abbondanza Pantaleo
- Principal Investigator Email
- maria.pantaleo@unibo.it
- Contact Person Name
- Maria Abbondanza Pantaleo
- Contact Person Email
- maria.pantaleo@unibo.it
- Site Name
- Fondazione IRCCS Istituto Nazionale Dei Tumori
- Department Name
- Medical Oncology
- Principal Investigator Name
- Silvia Stacchiotti
- Principal Investigator Email
- Silvia.Stacchiotti@istitutotumori.mi.it
- Contact Person Name
- Silvia Stacchiotti
- Contact Person Email
- Silvia.Stacchiotti@istitutotumori.mi.it
- Site Name
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Department Name
- Sarcomas and Rare Tumor Unit
- Principal Investigator Name
- Salvatore Tafuto
- Principal Investigator Email
- s.tafuto@istitutotumori.na.it
- Contact Person Name
- Salvatore Tafuto
- Contact Person Email
- s.tafuto@istitutotumori.na.it
Netherlands
- Earliest CTIS Part Ii Submission Date
- 19-08-2025
- Latest Decision Or Authorization Date
- 20-02-2026
- Processing Time Days
- 185
- Number Of Sites
- 3
- Number Of Participants
- 7
Sites
- Site Name
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Department Name
- Medical Oncology
- Principal Investigator Name
- Fredericus Albert Louis Maria Eskens
- Principal Investigator Email
- f.eskens@erasmusmc.nl
- Contact Person Name
- Fredericus Albert Louis Maria Eskens
- Contact Person Email
- f.eskens@erasmusmc.nl
- Site Name
- Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
- Department Name
- Medical Oncology
- Principal Investigator Name
- Winette van der Graaf
- Principal Investigator Email
- w.vd.graaf@nki.nl
- Contact Person Name
- Winette van der Graaf
- Contact Person Email
- w.vd.graaf@nki.nl
- Site Name
- Leids Universitair Medisch Centrum (LUMC)
- Department Name
- Medical Oncology
- Principal Investigator Name
- André Johan Gelderblom
- Principal Investigator Email
- A.J.Gelderblom@lumc.nl
- Contact Person Name
- André Johan Gelderblom
- Contact Person Email
- A.J.Gelderblom@lumc.nl
Belgium
- Earliest CTIS Part Ii Submission Date
- 26-08-2025
- Latest Decision Or Authorization Date
- 17-02-2026
- Processing Time Days
- 175
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- Cliniques Universitaires Saint-Luc
- Department Name
- Medical Oncology
- Principal Investigator Name
- Filomena Mazzeo
- Principal Investigator Email
- filomena.mazzeo@saintluc.uclouvain.be
- Contact Person Name
- Filomena Mazzeo
- Contact Person Email
- filomena.mazzeo@saintluc.uclouvain.be
Sponsor
Primary sponsor
- Full Name
- Springworks Therapeutics Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- MEDPACE LABORATORIES
- Responsibilities
- Laboratory/Research/Testing facility – sponsorDuties codes: ["4"]; contact: RS-Advisor-Support@medpace.com
- Name
- Medpace Finland Oy
- Responsibilities
- Clinical operations/regulatory support – sponsorDuties codes: ["1","2","3","5"]; contact: RS-Advisor-Support@medpace.com
- Name
- PCI Pharma Services Germany GmbH
- Responsibilities
- Logistics/shipments – sponsorDuties codes: ["14"]; contact: shipments-BER@pci.com
Third parties
- {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [\"7\"]; contact: patientcloudsupport@mdsol.com","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Adelphi Values Limited","duties_or_roles":"sponsorDuties codes: [\"15\" (Optional Participant Qualitative Interview), \"7\"]; contact: info@adelphivalues.com","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"sponsorDuties codes: [\"4\"]; contact: RS-Advisor-Support@medpace.com","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"sponsorDuties codes: [\"14\"]; contact: shipments-BER@pci.com","organisation_type":"Pharmaceutical company"}
- {"country":"Switzerland","full_name":"United BioSource (Suisse) S.A.","duties_or_roles":"sponsorDuties codes: [\"8\"]; contact: pv@springworkstx.com","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"United Biosource LLC","duties_or_roles":"sponsorDuties codes: [\"8\"]; contact: pv@springworkstx.com","organisation_type":"Pharmaceutical company"}
- {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"sponsorDuties codes: [\"1\",\"2\",\"3\",\"5\"]; contact: RS-Advisor-Support@medpace.com","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"sponsorDuties codes: [\"15\" (Trial Master File Management)]; contact: all_hq@veeva.com","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"sponsorDuties codes: [\"15\" (Site Payment, Patient Travel Arrangements and Reimbursement)]; contact: support@greenphire.com","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Andersonbrecon (UK) Limited","duties_or_roles":"sponsorDuties codes: [\"14\"]; contact: Theresa.Twohig@pci.com","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Nirogacestat
- Active Substance
- NIROGACESTAT HYDROBROMIDE
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Authorised
- Orphan Designation
- Yes
- Maximum Dose
- 300 mg
- Investigational Product Name
- Nirogacestat
- Active Substance
- NIROGACESTAT HYDROBROMIDE
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Authorised
- Orphan Designation
- Yes
- Maximum Dose
- 300 mg
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