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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04195399




Registration number
NCT04195399
Ethics application status
Date submitted
20/11/2019
Date registered
11/12/2019
Date last updated
6/03/2024

Titles & IDs
Public title
A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery
Scientific 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
Secondary ID [1] 0 0
NCI-2019-07498
Secondary ID [2] 0 0
ARST1921
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Desmoid Fibromatosis 0 0
Recurrent Desmoid Fibromatosis 0 0
Unresectable Desmoid Fibromatosis 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Biospecimen Collection
Treatment: Surgery - Computed Tomography
Treatment: Surgery - Echocardiography
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Drugs - Nirogacestat
Other interventions - Quality-of-Life Assessment
Other interventions - Questionnaire Administration
Treatment: Surgery - X-Ray Imaging

Experimental: 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.


Treatment: Surgery: Biospecimen Collection
Undergo blood sample collection

Treatment: Surgery: Computed Tomography
Undergo CT

Treatment: Surgery: Echocardiography
Undergo ECHO

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Treatment: Drugs: Nirogacestat
Given PO

Other interventions: Quality-of-Life Assessment
Ancillary studies

Other interventions: Questionnaire Administration
Ancillary studies

Treatment: Surgery: X-Ray Imaging
Undergo x-ray
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS)
Timepoint [1] 0 0
From initiation of treatment to occurrence of disease progression or death from any cause, assessed up to 2 years
Primary outcome [2] 0 0
Incidence of adverse events
Timepoint [2] 0 0
Up to 2 years
Primary outcome [3] 0 0
Pharmacokinetic (PK) parameter: systemic exposure
Timepoint [3] 0 0
Up to Cycle 3 (each cycle lasts 28 days)
Primary outcome [4] 0 0
PK parameter: drug clearance
Timepoint [4] 0 0
Up to Cycle 3 (each cycle lasts 28 days)
Primary outcome [5] 0 0
PK parameter: half-life
Timepoint [5] 0 0
Up to Cycle 3 (each cycle lasts 28 days)
Secondary outcome [1] 0 0
Objective response rate
Timepoint [1] 0 0
Up to 24 months

Eligibility
Key inclusion criteria
- 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

- 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
Minimum age
12 Months
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
35
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [3] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
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Delaware
Country [8] 0 0
United States of America
State/province [8] 0 0
District of Columbia
Country [9] 0 0
United States of America
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Florida
Country [10] 0 0
United States of America
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Georgia
Country [11] 0 0
United States of America
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Hawaii
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United States of America
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Idaho
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United States of America
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Illinois
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United States of America
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Indiana
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United States of America
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Kentucky
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United States of America
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Louisiana
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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Michigan
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United States of America
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Mississippi
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United States of America
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Missouri
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Nevada
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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United States of America
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Oregon
Country [29] 0 0
United States of America
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Pennsylvania
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United States of America
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Rhode Island
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United States of America
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South Carolina
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Utah
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United States of America
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Virginia
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United States of America
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Wisconsin
Country [37] 0 0
Canada
State/province [37] 0 0
Alberta
Country [38] 0 0
Canada
State/province [38] 0 0
Quebec
Country [39] 0 0
New Zealand
State/province [39] 0 0
Auckland
Country [40] 0 0
New Zealand
State/province [40] 0 0
Christchurch
Country [41] 0 0
Puerto Rico
State/province [41] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
SpringWorks Therapeutics, Inc.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT04195399
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Fariba Navid
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04195399