A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery
A Safety, Pharmacokinetic and Efficacy Study of a y-Secretase Inhibitor, Nirogacestat (PF-03084014), in Children and Adolescents With Progressive, Surgically Unresectable Desmoid Tumors
3 other identifiers
interventional
31
5 countries
98
Brief Summary
This phase II trial studies the side effects and how well nirogacestat works in treating patients less than 18 years of age with desmoid tumors that has grown after at least one form of treatment by mouth or in the vein that cannot be removed by surgery. Nirogacestat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Oct 2020
Longer than P75 for phase_2
98 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 20, 2019
CompletedFirst Posted
Study publicly available on registry
December 11, 2019
CompletedStudy Start
First participant enrolled
October 7, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
April 10, 2027
ExpectedApril 15, 2026
April 1, 2026
5.5 years
November 20, 2019
April 13, 2026
Conditions
Outcome Measures
Primary Outcomes (5)
Progression-free survival (PFS)
Will be estimated using the Kaplan-Meier method with the 95% confidence interval estimated by the Peto-Peto method.
From initiation of treatment to occurrence of disease progression or death from any cause, assessed up to 2 years
Incidence of adverse events
Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All grade 3 or above toxicities deemed related to study drug will be summarized. All grade 1 and 2 toxicities observed in \> 5% of participants and deemed related to study drug will be reported.
Up to 2 years
Pharmacokinetic (PK) parameter: systemic exposure
PK parameters of nirogacestat will be defined to quantify systemic exposure, drug clearance, terminal half-life and other pharmacokinetic characteristics. These PK parameters will be summarized with descriptive statistics, including means, medians, ranges, and standard deviations.
Up to Cycle 3 (each cycle lasts 28 days)
PK parameter: drug clearance
PK parameters of nirogacestat will be defined to quantify systemic exposure, drug clearance, terminal half-life and other pharmacokinetic characteristics. These PK parameters will be summarized with descriptive statistics, including means, medians, ranges, and standard deviations.
Up to Cycle 3 (each cycle lasts 28 days)
PK parameter: half-life
PK parameters of nirogacestat will be defined to quantify systemic exposure, drug clearance, terminal half-life and other pharmacokinetic characteristics. These PK parameters will be summarized with descriptive statistics, including means, medians, ranges, and standard deviations.
Up to Cycle 3 (each cycle lasts 28 days)
Secondary Outcomes (1)
Objective response rate
Up to 24 months
Other Outcomes (5)
CTNNB1 and APC gene mutations and genomic signatures
Up to 2 years
Changes in the levels of each of the lymphocyte subsets and immunoglobulins
Up to 2 years
Response assessments by the RECIST criteria
Up to cycle 24
- +2 more other outcomes
Study Arms (1)
Treatment (nirogacestat)
EXPERIMENTALPatients 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.
Interventions
Undergo blood sample collection
Undergo CT
Undergo ECHO
Undergo MRI
Given PO
Ancillary studies
Undergo x-ray
Eligibility Criteria
You may qualify if:
- Patients must be \> 12 months and \< 18 years of age at the time of enrollment
- 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
- +26 more criteria
You may not qualify if:
- Active or chronic infection within 7 days prior to study entry
- 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
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Children's Oncology Grouplead
- National Cancer Institute (NCI)collaborator
- SpringWorks Therapeutics, Inc.collaborator
Study Sites (98)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
USA Health Strada Patient Care Center
Mobile, Alabama, 36604, United States
Banner Children's at Desert
Mesa, Arizona, 85202, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
Kaiser Permanente Downey Medical Center
Downey, California, 90242, United States
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Mattel Children's Hospital UCLA
Los Angeles, California, 90095, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, 94304, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Rady Children's Hospital - San Diego
San Diego, California, 92123, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218, United States
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
AdventHealth Orlando
Orlando, Florida, 32803, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Children's Hospital New Orleans
New Orleans, Louisiana, 70118, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Michigan State University
East Lansing, Michigan, 48823, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
University Medical Center of Southern Nevada
Las Vegas, Nevada, 89102, United States
Sunrise Hospital and Medical Center
Las Vegas, Nevada, 89109, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135, United States
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144, United States
Renown Regional Medical Center
Reno, Nevada, 89502, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Albany Medical Center
Albany, New York, 12208, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Penn State Children's Hospital
Hershey, Pennsylvania, 17033, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
El Paso Children's Hospital
El Paso, Texas, 79905, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
Carilion Children's
Roanoke, Virginia, 24014, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
The Children's Hospital at Westmead
Westmead, New South Wales, 2145, Australia
Queensland Children's Hospital
South Brisbane, Queensland, 4101, Australia
Perth Children's Hospital
Perth, Western Australia, 6009, Australia
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8, Canada
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7, Canada
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3, Canada
Starship Children's Hospital
Grafton, Auckland, 1145, New Zealand
Christchurch Hospital
Christchurch, 8011, New Zealand
University Pediatric Hospital
San Juan, 00926, Puerto Rico
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Fariba Navid
Children's Oncology Group
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 20, 2019
First Posted
December 11, 2019
Study Start
October 7, 2020
Primary Completion
March 31, 2026
Study Completion (Estimated)
April 10, 2027
Last Updated
April 15, 2026
Record last verified: 2026-04