TumorPhase 2NCT05879146
Evaluation of the Response and Non-response of Nirogacestat in Desmoid Tumors- Clinical Study
A Phase 2 study testing Nirogacestat in people with Tumor, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To learn about the safety and effects of an investigational drug called nirogacestat when given to participants with a desmoid tumor/aggressive fibromatosis Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tumor
- 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
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Nov 2024to 31 Jan 2028
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- This study will enroll approximately 40 participants diagnosed with DT. Participants must meet the following eligibility criteria to be enrolled:
- Age ≥ 18 years. Individuals younger than 18 years old are excluded. More than 99% of the population evaluated at MDACC with a diagnosis of DT is older than 18. Sixty-three percent of the population with a diagnosis of DT evaluated at MDACC are 10 - 54 years old. The remaining 37 percent are older than 54 years old. Additionally, most of the robust data related to dosing or adverse event data currently available on the use of nirogacestat is in adults
- Histologically documented DT with evidence of radiographic tumor progression (≥ 10% or absolute increase in dimensions of ≥ 10 mm in maximal diameter) in unidimensional measurement within the previous 18 months. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam
- Recurrent or primary disease
- Symptomatic disease or impending morbidity (as defined by physician) and patient and physician agree treatment would be of benefit
- Treatment naïve or progression on or after any prior therapy for DT. Participant must have discontinued prior therapy for at least 28 days or 5 half-lives of the drug, whichever is greater. All toxicities from prior therapy must be resolved to Grade ≤ 1 or clinical baseline. There is no limit on the number of previous systemic treatments received
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- Able to tolerate radiographic progression (up to 20% increase in tumor longest diameter) as determined by treating oncologist based on morbidity and tumor growth is not threatening vital structures
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Are appropriate for systemic therapy
- Have accessible tumors for serial biopsies
- Agree to provide new tumor tissue. Tumor tissue from the archival (tumor bank) may be used if the biopsy is performed after discontinuation of prior therapy and the participant must have discontinued prior therapy for at least 28 days or five half-lives of the drug, whichever is greater
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Adequate organ and bone marrow function as defined by the following screening laboratory values:
- Absolute neutrophil count ≥ 1500 cells/μL;
- Platelets ≥ 100,000 μL;
- Hemoglobin ≥ 9 g/dL;
- Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%);
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase)/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase) ≤ 2 × ULN; and
- If Creatinine > 1.5 x ULN then calculated creatinine clearance must be . 60 mL/min (using the Cockcroft-Gault formula).
- Can swallow tablets and have no gastrointestinal conditions affecting absorption
- Agree to the use of adequate contraception during the treatment period and for at least 4 months for men and women after the last dose of the study treatment (see Appendix 1 for more information)
- Have the ability to understand and the willingness to sign a written informed consent document
- English and non-English speaking patients
- Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this study
- Participants with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification; to be eligible for this study, participants should be class 2B or better
Who cannot join
- Participants are excluded from this study if any of the following criteria apply:
- Unable to undergo serial biopsies
- Participants with familial adenomatous polyposis
- Unable to tolerate MRI or for whom MRI is contraindicated
- Pregnant or breastfeeding women are excluded from this study. Based on findings in animal studies, oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than adult human exposures at the recommended dose of 150 mg twice daily. Nirogacestat should be avoided during pregnancy
- There is no data regarding the presence of nirogacestat or its metabolites in either human or animal milk or its effects on a breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child from nirogacestat, advise women not to breastfeed during treatment with nirogacestat.
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- Known hypersensitivity to nirogacestat or any of its excipients
- Participants requiring the use of any excluded concomitant medications listed in Table 2 during the course of the study
- Unable to comply with study-related procedures in the opinion of the investigator
- Patients with cognitive impairment requiring a legally authorized representative for consent
- Patients with uncontrolled intercurrent illness (Indicate clearly what type or extent)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with positive viral load will be excluded
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia
- Patients who are receiving any other investigational agents
- Patients with an additional malignancy and brain metastases. There is not enough evidence of the effects of nirogacestat in other malignancies at this time
- Participant has experienced any of the following within 6 months of signing informed consent:
- 15.1 clinically significant cardiac disease (New York Heart Association Class III or IV); 15.2 myocardial infarction; 15.3 severe/unstable angina; 15.4 coronary/peripheral artery bypass graft; 15.5 symptomatic congestive heart failure; 15.6 cerebrovascular accident; 15.7 transient ischemic attack; or 15.8 symptomatic pulmonary embolism.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
M D Anderson Cancer Center
Houston, Texas, 77030
Keila Torres, MD, PHD, 713-792-4242, ketorres@mdanderson.org
Keila Torres, MD, PHD
About this study
To learn about the safety and effects of an investigational drug called nirogacestat when given to participants with a desmoid tumor/aggressive fibromatosis
Read the detailed description
Primary Objectives:
- To identify biomarkers associated with response and non-response to nirogacestat in participants with desmoid tumors (DT).
Secondary Objectives:
- To assess the 12-month progression-free survival (PFS of participants with DT who receive nirogacestat at 150 mg or 100 mg BID.
- To assess MRI volumetric and functional parameters associated with response and non-response to nirogacestat in participants with DT.
- To evaluate the histopathological changes in DT biopsy specimens.
- To evaluate the safety and tolerability of nirogacestat in participants with DT.
Exploratory Objectives:
- To assess clinical benefit and tumor response by additional MRI-based measurements including MRI-modified Choi criteria and WHO.
- To evaluate MRI parameters such as intensity histogram analysis from T2-weighted image (T2-WI), short inversion time inversion-recovery (T2-STIR), diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping, post-contrast Water Dixon, perfusion-weighted imaging, and susceptibility-weighted imaging (SWI) with contrast and correlate with therapeutic response and clinical outcome.
- To assess the dynamics and concordance of circulating tumor cells (CTCs) in the blood compartment and tumor burden during nirogacestat treatment.
- To identify cell-free DNA (cfDNA) biomarkers associated with response and non-response to nirogacestat in patients with DT.
- To understand the impact of dose on the incidence of ovarian dysfunction in women of childbearing potential (WOCBP).
- Conditions
- Tumor
- Being tested
- Nirogacestat
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NirogacestatDrug
Given by PO
| Study group | Role | What they receive |
|---|---|---|
| nirogacestat | Experimental | Participants will take nirogacestat by mouth every day of each 28-day study cycle. Based on when you enroll in this study, you will take nirogacestat either 1 time a day at about the same time each day OR 2 times a day, about 12 hours apart. Receives: Drug: Nirogacestat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: through study completion; an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2023
- Study start26 Nov 2024
- Primary completion31 Jan 2027 (estimated)
- Study completion31 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TumorStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Keila Torres, MD,PHD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05879146
- Sponsor's protocol ID
- 2022-0610
- Other IDs
- NCI-2023-04177
- Status last verified
- Aug 2026
- First submitted
- 18 May 2023
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Response and Non-response of Nirogacestat in Desmoid Tumors- Clinical Study
- ClinicalTrials.gov ID
- NCT05879146
- Acronym / sponsor ID
- 2022-0610
- Conditions
- Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Study start
- 26 Nov 2024 (actual)
- Primary completion
- 31 Jan 2027 (estimated)
- Study completion
- 31 Jan 2028 (estimated)
- First posted
- 30 May 2023 (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.
To learn about the safety and effects of an investigational drug called nirogacestat when given to participants with a desmoid tumor/aggressive fibromatosis
Detailed description
Primary Objectives:
- To identify biomarkers associated with response and non-response to nirogacestat in participants with desmoid tumors (DT).
Secondary Objectives:
- To assess the 12-month progression-free survival (PFS of participants with DT who receive nirogacestat at 150 mg or 100 mg BID.
- To assess MRI volumetric and functional parameters associated with response and non-response to nirogacestat in participants with DT.
- To evaluate the histopathological changes in DT biopsy specimens.
- To evaluate the safety and tolerability of nirogacestat in participants with DT.
Exploratory Objectives:
- To assess clinical benefit and tumor response by additional MRI-based measurements including MRI-modified Choi criteria and WHO.
- To evaluate MRI parameters such as intensity histogram analysis from T2-weighted image (T2-WI), short inversion time inversion-recovery (T2-STIR), diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping, post-contrast Water Dixon, perfusion-weighted imaging, and susceptibility-weighted imaging (SWI) with contrast and correlate with therapeutic response and clinical outcome.
- To assess the dynamics and concordance of circulating tumor cells (CTCs) in the blood compartment and tumor burden during nirogacestat treatment.
- To identify cell-free DNA (cfDNA) biomarkers associated with response and non-response to nirogacestat in patients with DT.
- To understand the impact of dose on the incidence of ovarian dysfunction in women of childbearing potential (WOCBP).
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: NirogacestatParticipants will take nirogacestat by mouth every day of each 28-day study cycle. Based on when you enroll in this study, you will take nirogacestat either 1 time a day at about the same time each day OR 2 times a day, about 12 hours apart. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- This study will enroll approximately 40 participants diagnosed with DT. Participants must meet the following eligibility criteria to be enrolled:
- Age ≥ 18 years. Individuals younger than 18 years old are excluded. More than 99% of the population evaluated at MDACC with a diagnosis of DT is older than 18. Sixty-three percent of the population with a diagnosis of DT evaluated at MDACC are 10 - 54 years old. The remaining 37 percent are older than 54 years old. Additionally, most of the robust data related to dosing or adverse event data currently available on the use of nirogacestat is in adults
- Histologically documented DT with evidence of radiographic tumor progression (≥ 10% or absolute increase in dimensions of ≥ 10 mm in maximal diameter) in unidimensional measurement within the previous 18 months. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam
- Treatment naïve or progression on or after any prior therapy for DT. Participant must have discontinued prior therapy for at least 28 days or 5 half-lives of the drug, whichever is greater. All toxicities from prior therapy must be resolved to Grade ≤ 1 or clinical baseline. There is no limit on the number of previous systemic treatments received
- Able to tolerate radiographic progression (up to 20% increase in tumor longest diameter) as determined by treating oncologist based on morbidity and tumor growth is not threatening vital structures
Key exclusion criteria (18 listed)
- Unable to undergo serial biopsies
- Participants with familial adenomatous polyposis
- Unable to tolerate MRI or for whom MRI is contraindicated
- Pregnant or breastfeeding women are excluded from this study. Based on findings in animal studies, oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than adult human exposures at the recommended dose of 150 mg twice daily. Nirogacestat should be avoided during pregnancy
- There is no data regarding the presence of nirogacestat or its metabolites in either human or animal milk or its effects on a breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child from nirogacestat, advise women not to breastfeed during treatment with nirogacestat.
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 |
|---|---|---|
| NirogacestatGiven by PO | Drug | nirogacestat |
Primary outcome
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Time frame: through study completion; an average of 1 year.
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 10 Aug 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
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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.
Keila Torres, MD,PHD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nirogacestat in people with Tumor, run by M.D. Anderson Cancer Center at 1 site in United States.
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 26 inclusion and 18 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 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Keila Torres, MD,PHD ((713) 792-4242, ketorres@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: through study completion; an average of 1 year.). 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 10 Aug 2026.