Study of Cryoablation and Nirogacestat for Desmoid Tumor

NCT05949099 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: IRB-67799NCI-2023-05590
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this protocol is Systemic therapy with oral study agent, nirogacestat, followed by a single cryoablation procedure.

Conditions

Desmoid Tumor

Keywords

Desmoid; Cryoablation; Nirogacestat

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit per RECIST v1.1

  Clinical benefit (CB) is defined as the number of participants assessed with a complete response (CR), partial response (PR), or stable disease (SD) within 1 year and with no evidence of loss of response nor progression within that year. Response \& progression will be assessed according to the Revised Response Evaluation Criteria in Solid Tumors (RECIST)v1.1, as follows: RECIST v1.1: * CR=Disappearance of all lesions * PR=≥30% decrease in diameter of target lesions * Progressive disease (PD)=20% increase in diameter of target lesion; progression of non-target lesion; or ≥1 new lesion(s) For the overall outcome: * SD=Changes not meeting above criteria * Overall Response (OR)=CR+PR * CB=CR+PR+SD

  1 year

Secondary Outcomes (6)

• Clinical Benefit per mRECIST

  1 year

• Progression-free Survival (PFS)

  1 year

• Objective Response

  1 year

• Time-to-Response (TTR)

  1 year

• Duration of Response (DoR)

  1 year

Study Arms (1)

Nirogacestat 150 mg

EXPERIMENTAL

Patients will receive 3-cycle lead-in with systemic therapy with nirogacestat 150 mg po BID, given continuously.

Drug: Nirogacestat; Procedure: Cryoablation

Interventions

Nirogacestat DRUG

Nirogacestat 150 mg by mouth twice-daily continuously for Cycles 1 through 3. Treatment with nirogacestat may continue via this study protocol for up to 24 months (26 cycles of treatment), unless there is progression of disease, intolerance, start of new anticancer therapy, or Subject Study Completion or Termination occurs.

Nirogacestat 150 mg

Cryoablation PROCEDURE

Cryoablation procedure (single session) of one tumor mass between Cycles 3 and 4 of nirogacestat treatment

Nirogacestat 150 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-confirmed diagnosis of desmoid tumor (DT) that is progressing (by RECIST criteria over the past 12 months) or symptomatic (as defined by change in pain regimen or impairment of activities of daily living (ADLs), or at investigator discretion). Note: Must have diagnosis of desmoid tumor on pathology report.
• Desmoid tumor is 50 to \<75% cryoablatable.
• Tumors that are 50 to \<75% (volume) ablatable in a single session are characterized by:
• Proximity (\< 1 cm) to critical structures, such as nerves, vessels, bowel, or skin, at risk of injury during ablation, despite hydrodissection
• Large size ( \> 100 mL)
• Complex shape, such that parts of the tumor cannot be reached from a single approach or subject position
• Thin, infiltrative components, where ablation of that portion would damage more normal anatomy than tumor (e.g., tumor extending along a fascial plane between muscles, such that ablation would damage more muscle than tumor volume)
• If participant is currently being treated with any therapy for the treatment of DT, this must be completed at least 28 days (or 5 half-lives, whichever is shorter) prior to first dose of study treatment. All toxicities from prior therapy must be resolved to ≤ Grade 1 or clinical baseline.
• Participants who are receiving chronic nonsteroidal anti-inflammatory drugs (NSAIDs) as treatment for conditions other than DT must be on a stable dose for at least 28 days prior to first dose of study treatment.
• Age ≥ 18 years.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening.
• Participant has adequate organ and bone marrow function as defined by the following screening laboratory values:
• Absolute neutrophil count ≥ 1500 cells/μL;
• Platelets ≥ 100,000μL;
• Hemoglobin ≥ 9 g/dL;

You may not qualify if:

• Participant previously received or is currently receiving therapy with GS inhibitors or anti-Notch antibody therapy.
• Participant is currently using or anticipates using food or drugs that are known strong or moderate cytochrome P450 3A4 (CYP3A4) inhibitors, or strong CYP3a inducers within 14 days prior to the first dose of study treatment.
• Participant has known hypersensitivity to the active substance or to any of the excipients of nirogacestat.
• Participant with active or chronic infection at the time of informed consent and during the screening period.
• Participant has known malabsorption syndrome or preexisting gastrointestinal condition that may impair absorption of nirogacestat (e.g., gastric bypass, lap band, or other gastric procedures that would alter absorption); delivery of nirogacestat via nasogastric tube or gastrostomy tube is not allowed.
• History of other high-grade malignancy ≤ 2 years previous. Exceptions include 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; adequately treated basal cell or squamous cell skin cancer; or adequately treated, with curative intent, cancer from which the subject is currently in complete remission per study Principal Investigator's (PI's) judgment. Specific situations can be discussed with study PI.
• 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

Sponsors & Collaborators

• Nam Bui: lead
• SpringWorks Therapeutics, Inc.: collaborator

Study Sites (1)

Stanford University

Palo Alto, California, 94395, United States

RECRUITING

MeSH Terms

Conditions

Desmoid Tumors

Interventions

nirogacestat; Cryosurgery

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Nam Bui, M.D.

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Priyanka Reddy

CONTACT

(650) 497-8288; reddyp@stanford.edu

Amir Emami

CONTACT

650-723-2868; amir.emami@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate Professor, Medicine - Oncology

Study Record Dates

• First Submitted: July 7, 2023
• First Posted: July 17, 2023
• Study Start: August 15, 2023
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)