A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery
NCT ID: NCT04195399
Last Updated: 2026-02-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2
35 participants
INTERVENTIONAL
2020-10-07
2032-12-31
Brief Summary
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Detailed Description
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I. To estimate the 2-year progression-free survival (PFS) rate in patients with progressive, surgically unresectable desmoid tumor treated with nirogacestat.
II. To describe the toxicities of nirogacestat in children and adolescents with desmoid tumor.
III. To characterize the pharmacokinetics (PK) of nirogacestat in children and adolescents.
SECONDARY OBJECTIVE:
I. To determine the objective tumor response rate (ORR) of nirogacestat in children and adolescents with progressive, surgically unresectable desmoid tumor.
EXPLORATORY OBJECTIVES:
I. To collect blood, archival tumor samples and on-study/post-treatment tumor samples (if available) from patients enrolled on this trial to correlate various CTNNB1 and APC gene mutations and genomic signatures with tumor response and PFS.
II. To explore the effect of nirogacestat on immune cells and immunoglobulin levels in the peripheral blood.
III. To collect blood samples for banking at baseline, during treatment, and at the time of progression for future research.
IV. To compare assessment of tumor response using Response Evaluation Criteria in Solid Tumors (RECIST), World Health Organization (WHO) criteria, and T2 and volumetric changes using magnetic resonance imaging (MRI).
V. To utilize a tool developed to specifically assess patient reported outcomes (PROs) in adult patients with desmoid tumor (GOunder/DTRF DEsmoid Symptom/Impact Scale \[GODDESS\]) and the Patient Reported Outcomes Measurement Information System (PROMIS) to explore the relationship between PROs and tumor response and PFS.
OUTLINE:
Patients receive nirogacestat orally (PO) twice daily (BID) on days 1-28. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) and computed tomography (CT) or MRI on study. Patients may also undergo x-ray imaging and blood sample collection on study.
After completion of study treatment, patients are followed up at 30 days.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (nirogacestat)
Patients receive nirogacestat PO BID on days 1-28. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO and CT or MRI on study. Patients may also undergo x-ray imaging and blood sample collection on study.
Biospecimen Collection
Undergo blood sample collection
Computed Tomography
Undergo CT
Echocardiography Test
Undergo ECHO
Magnetic Resonance Imaging
Undergo MRI
Nirogacestat
Given PO
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
X-Ray Imaging
Undergo x-ray
Interventions
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Biospecimen Collection
Undergo blood sample collection
Computed Tomography
Undergo CT
Echocardiography Test
Undergo ECHO
Magnetic Resonance Imaging
Undergo MRI
Nirogacestat
Given PO
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies
X-Ray Imaging
Undergo x-ray
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patients must have a body surface area of \> 0.3 m\^2 at the time of enrollment
* Existing or recurrent desmoid tumor that is deemed not amenable to surgery without significant morbidity and progressed by \>= 10% as assessed by RECIST version (v)1.1 within the 6-month period prior to study enrollment
* Patients must have had histologic verification of the desmoid tumor
* Patients must have measurable disease by RECIST v1.1 criteria
* Patient must have received at least one prior course of systemic therapy for desmoid tumor
* Patients must have a Lansky (for patients =\< 16 years of age) or Karnofsky (for patients \> 16 years of age) performance status score of \>= 50. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing performance score
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, surgery or radiotherapy prior to entering this study. Patients may not be using or anticipate using these treatments after the observed progression or within the time period stated below
* Cytotoxic chemotherapy: must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea)
* Small molecule tyrosine kinase inhibitors (e.g., sorafenib, pazopanib, imatinib), rapalogs (e.g., temsirolimus, everolimus, sirolimus) or anti estrogen therapy (e.g., tamoxifen): may not have received within 28 days prior to the first dose of study treatment
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent
* Local regional tumor directed therapy, including, but not limited to small port radiation therapy (RT), radiofrequency ablation, cryotherapy, surgery: at least 2 weeks since these therapies and all toxicity must have resolved to grade =\< 1. If prior craniospinal RT or if \>= 50% radiation of pelvis then \>= 6 months must have elapsed. If other substantial bone marrow (BM) radiation, then \>= 6 weeks must have elapsed
* Stem cell transplant (SCT): No evidence of active graft versus (vs.) host disease. For allogeneic SCT, \>= 6 months must have elapsed
* No prior gamma-secretase, Notch or beta-catenin inhibitor
* Investigational drugs: must not have received investigational drug within 4 weeks of study entry, and all toxicities related to prior therapy must be resolved to grade =\< 1 or baseline
* Concomitant Medication Restrictions
* Growth factor(s): must not have received within 1 week of entry onto this study
* Patients who are currently receiving drugs that are strong inducers or moderate or strong inhibitors of CYP3A4 are not eligible. Strong inducers or moderate or strong inhibitors of CYP3A4 are not allowed from 14 days prior to enrollment to the end of protocol therapy. Note: CYP3A4 inducing anti-epileptic drugs on a stable dose, are allowed
* Must not be receiving non-steroidal anti-inflammatory drugs (NSAIDs) as treatment for desmoid tumor after the observed progression and patient agrees to not use NSAIDs while on study. Occasional use (defined as =\< 3 times per week) for treatment of pain is permitted
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment)
* Platelet count \>= 100,000/uL (transfusion independent) (within 7 days prior to enrollment)
* Hemoglobin \>= 9.0 g/dL (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to enrollment)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
* Age: Maximum serum creatinine (mg/dL)
* Age: 1 to \< 2 years; Maximum serum creatinine (mg/dL): 0.6 (male and female)
* Age: 2 to \< 6 years; Maximum serum creatinine (mg/dL): 0.8 (male and female)
* Age: 6 to \< 10 years; Maximum serum creatinine (mg/dL): 1 (male and female)
* Age: 10 to \< 13 years; Maximum serum creatinine (mg/dL): 1.2 (male and female)
* Age: 13 to \< 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
* Age: \>= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
* Adequate liver function defined as:
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (unless secondary to previously diagnosed Gilbert's syndrome) (within 7 days prior to enrollment)
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L (within 7 days prior to enrollment)
* Adequate cardiac function defined as:
* Corrected QT (QTc) interval \< 470 ms
* No history of congenital or acquired prolonged QTc syndrome
* No history of clinically significant cardiac arrhythmias, congestive heart failure, stroke or myocardial infarction within 6 months prior to study entry
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria
* Presence of non-healing fracture
* Note: patients with pathologic fracture related to tumor are eligible
* Use of corticosteroids within 21 days of enrollment, except in the following situations:
* Physiologic steroid replacement for adrenal insufficiency
* Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption
* Short course (=\< 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen), or exacerbation of asthma
* Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption (e.g., inability to take oral medication, prior surgical procedures affecting absorption (e.g., gastric bypass), malabsorption syndrome, and active peptic ulcer disease)
* Patients with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction
* Known active infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
* Patients with a prior history of malignancy, with the exceptions of desmoid tumor(s) and non-melanoma skin cancer, who are not in remission for more than 3 years
* Patients who are unable to swallow tablets. Tablets must not be crushed or chewed. Administration of nirogacestat via gastrostomy tube or nasogastric tube is not allowed
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study
* Sexually active female patients of reproductive potential who have not agreed to use 1 method of highly effective contraceptive (including copper-containing intrauterine device, condom with spermicidal foam/gel/film/cream/suppository, bilateral tubal ligation, established use of inserted, injected or implanted hormonal method of contraception, abstinence, or male sterilization) for the duration of their study participation and for at least 6 months after last dose of nirogacestat. A second form of contraception (i.e. barrier method) is required for patients who are using hormonal contraception as nirogacestat may reduce the efficacy of hormonal contraceptives
* Sexually active male patients of reproductive potential who have not agreed to use a condom and their female partner who have not agreed to use one of the highly effective methods of contraception mentioned above during treatment and for at least 90 days after the last dose of nirogacestat
* Female patients who are breastfeeding
* Female patients who are pregnant. These patients are excluded because there is no available information regarding the effects of nirogacestat on the developing human fetus and inhibition of gamma-secretase is known to be teratogenic
* Female patients of childbearing potential unless a negative pregnancy test result has been obtained
12 Months
18 Years
ALL
No
Sponsors
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Children's Oncology Group
NETWORK
National Cancer Institute (NCI)
NIH
SpringWorks Therapeutics, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Fariba Navid
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
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Children's Hospital of Alabama
Birmingham, Alabama, United States
USA Health Strada Patient Care Center
Mobile, Alabama, United States
Banner Children's at Desert
Mesa, Arizona, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center
Downey, California, United States
Loma Linda University Medical Center
Loma Linda, California, United States
Children's Hospital Los Angeles
Los Angeles, California, United States
Mattel Children's Hospital UCLA
Los Angeles, California, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States
Kaiser Permanente-Oakland
Oakland, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, United States
Connecticut Children's Medical Center
Hartford, Connecticut, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
AdventHealth Orlando
Orlando, Florida, United States
Nemours Children's Hospital
Orlando, Florida, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, United States
Riley Hospital for Children
Indianapolis, Indiana, United States
Norton Children's Hospital
Louisville, Kentucky, United States
Children's Hospital New Orleans
New Orleans, Louisiana, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Michigan State University
East Lansing, Michigan, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Mercy Hospital Saint Louis
St Louis, Missouri, United States
University Medical Center of Southern Nevada
Las Vegas, Nevada, United States
Sunrise Hospital and Medical Center
Las Vegas, Nevada, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, United States
Summerlin Hospital Medical Center
Las Vegas, Nevada, United States
Renown Regional Medical Center
Reno, Nevada, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Albany Medical Center
Albany, New York, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
State University of New York Upstate Medical University
Syracuse, New York, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Dayton Children's Hospital
Dayton, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Oregon Health and Science University
Portland, Oregon, United States
Penn State Children's Hospital
Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
Providence, Rhode Island, United States
Medical University of South Carolina
Charleston, South Carolina, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, United States
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
El Paso Children's Hospital
El Paso, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
M D Anderson Cancer Center
Houston, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States
Carilion Children's
Roanoke, Virginia, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Queensland Children's Hospital
South Brisbane, Queensland, Australia
Perth Children's Hospital
Perth, Western Australia, Australia
Alberta Children's Hospital
Calgary, Alberta, Canada
University of Alberta Hospital
Edmonton, Alberta, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, Canada
Starship Children's Hospital
Grafton, Auckland, New Zealand
Christchurch Hospital
Christchurch, , New Zealand
University Pediatric Hospital
San Juan, , Puerto Rico
Countries
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Other Identifiers
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NCI-2019-07498
Identifier Type: REGISTRY
Identifier Source: secondary_id
ARST1921
Identifier Type: OTHER
Identifier Source: secondary_id
ARST1921
Identifier Type: OTHER
Identifier Source: secondary_id
ARST1921
Identifier Type: -
Identifier Source: org_study_id
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