for people ages 12 months to 18 years (full criteria)
at Oakland, California and other locations
study started
completion around



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.

Official Title

A Safety, Pharmacokinetic and Efficacy Study of a y-Secretase Inhibitor, Nirogacestat (PF-03084014), in Children and Adolescents With Progressive, Surgically Unresectable Desmoid Tumors



  1. 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.


  1. To determine the objective tumor response rate (ORR) of nirogacestat in children and adolescents with progressive, surgically unresectable desmoid tumor.


  1. 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).

  1. 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.


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.


Desmoid Fibromatosis, Recurrent Desmoid Fibromatosis, Unresectable Desmoid Fibromatosis, Aggressive Fibromatosis, Fibroma, Imidazole, Nirogacestat, Biospecimen Collection, Computed Tomography, Echocardiography, Magnetic Resonance Imaging, Quality-of-Life Assessment, X-Ray Imaging


You can join if…

Open to people ages 12 months to 18 years

  • 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 m2 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 m2 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:
  • 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

You CAN'T join 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
  • 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


  • UCSF Benioff Children's Hospital Oakland
    Oakland California 94609 United States
  • UCSF Medical Center-Mission Bay
    San Francisco California 94158 United States
  • Kaiser Permanente-Oakland
    Oakland California 94611 United States
  • Lucile Packard Children's Hospital Stanford University
    Palo Alto California 94304 United States


in progress, not accepting new patients
Start Date
Completion Date
Children's Oncology Group
Phase 2 Desmoid Tumor Research Study
Study Type
Expecting 35 study participants
Last Updated