Trial Title:
Study of Cryoablation and Nirogacestat for Desmoid Tumor
NCT ID:
NCT05949099
Condition:
Desmoid Tumor
Conditions: Official terms:
Fibromatosis, Aggressive
Nirogacestat
Conditions: Keywords:
Desmoid
Cryoablation
Nirogacestat
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Nirogacestat
Description:
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.
Arm group label:
Nirogacestat 150 mg
Intervention type:
Procedure
Intervention name:
Cryoablation
Description:
Cryoablation procedure (single session) of one tumor mass between Cycles 3 and 4 of
nirogacestat treatment
Arm group label:
Nirogacestat 150 mg
Summary:
The primary purpose of this protocol is Systemic therapy with oral study agent,
nirogacestat, followed by a single cryoablation procedure.
Detailed description:
The primary purpose of this protocol is treatment. Systemic therapy with oral study
agent, nirogacestat, will be given for 3 cycles (1 cycle = 28 days) followed by a single
cryoablation procedure between Cycles 3 and 4, and then continued nirogacestat for Cycles
4 through 26. Treatment with nirogacestat may continue via this study for up to 24 months
(26 cycles of treatment), unless there is progression of disease, intolerance, subject
withdraws their consent, start of a new anticancer therapy, or until Subject Study
Completion or Termination occurs.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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.
2. Desmoid tumor is 50 to <75% cryoablatable.
Tumors that are 50 to <75% (volume) ablatable in a single session are characterized
by:
1. Proximity (< 1 cm) to critical structures, such as nerves, vessels, bowel, or
skin, at risk of injury during ablation, despite hydrodissection
2. Large size ( > 100 mL)
3. Complex shape, such that parts of the tumor cannot be reached from a single
approach or subject position
4. 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)
3. 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.
4. 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.
5. Age ≥ 18 years.
6. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
at screening.
7. Participant has adequate organ and bone marrow function as defined by the following
screening laboratory values:
1. Absolute neutrophil count ≥ 1500 cells/μL;
2. Platelets ≥ 100,000μL;
3. Hemoglobin ≥ 9 g/dL;
4. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (isolated bilirubin > 1.5 ×
ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%);
5. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic
transaminase)/alanine aminotransferase (ALT) (serum glutamic pyruvate
transaminase) ≤ 2 × ULN; and
6. Serum creatinine ≤ 1.5 × ULN or if creatinine > 1.5 × ULN then calculated
creatinine clearance must be ≥ 60 mL/min (using the Cockcroft-Gault formula)
8. Women of childbearing potential must have a negative serum pregnancy test at
screening.
9. Participant can swallow tablets.
10. Participant able to have MRI.
11. Ability to understand and the willingness to personally sign the written
IRB-approved informed consent document.
12. Contraceptive use by men or women should be consistent with the standard that will
be used at Stanford regarding the methods of contraception for those participating
in clinical studies.
1. Male participants: Male participants are eligible to participate if they agree
to the following during the treatment period and for at least 90 days after the
last dose of study treatment:
• Refrain from donating or preserving sperm;
PLUS either:
- Be abstinent from sexual intercourse as their preferred and usual
lifestyle (abstinent on a long-term and persistent basis) and agree to
remain abstinent; OR
- Must agree to use a male condom when having sexual intercourse with women
of childbearing potential (WOCBP). An additional form of contraception as
described in Appendix G should also be used by the female partner, if she
is of childbearing potential.
Postmenopausal state (not of childbearing potential) is defined as no menses
for 12 months without an alternative medical cause.
2. Female participants: A female participant is eligible to participate if she is
not pregnant or breastfeeding, and at least one of the following conditions
applies:
- Is not of childbearing potential (not WOCBP). OR
- Is of childbearing potential but is abstinent or using 1 highly effective
contraceptive method, as described in Appendix H during the treatment
periodand for at least
1 week after the last dose of active study treatment. A second method of
contraception is required if the participant is using hormonal
contraception, as coadministration with nirogacestat may alter the plasma
concentrations of hormonal contraceptives resulting reduced efficacy.
Additionally, the participant agrees not to harvest or donate eggs (ova,
oocytes) for the purpose of reproduction during the treatment period and
for at least 6 months after the last dose of active study treatment. The
investigator should evaluate the effectiveness of the contraceptive method
in relationship to the first dose of study treatment.
- The investigator is responsible for review of medical history, menstrual
history, and recent sexual activity to decrease the risk for inclusion of
a woman with an early undetected pregnancy.
Exclusion Criteria:
1. Participant previously received or is currently receiving therapy with GS inhibitors
or anti-Notch antibody therapy.
2. Participant is currently using any treatment for DT including tyrosine kinase
inhibitors (TKIs), NSAIDS (chronic daily use - except as in inclusion criterion 4)
or any investigational treatment 28 days (or 5 half-lives, whichever is longer)
prior to the first dose of study treatment.
3. 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.
4. Participant has known hypersensitivity to the active substance or to any of the
excipients of nirogacestat.
5. Participant with active or chronic infection at the time of informed consent and
during the screening period.
6. 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.
7. 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.
8. 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
9. Participant has congenital long QT syndrome.
10. Participant has a history of additional risk factors for Torsades de pointes (TdP)
(e.g., heart failure, hypokalemia, family history of long QT syndrome).
11. Participant has current or chronic history of liver disease or known hepatic or
biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).
12. Participant is currently enrolled or was enrolled within 28 days of first dose of
study treatment in another clinical study with any investigational drug or device.
All subject files must include supporting documentation to confirm subject eligibility.
The method of confirmation can include, but is not limited to, laboratory test results,
radiology test results, subject self-report, and medical record review.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Stanford University
Address:
City:
Palo Alto
Zip:
94395
Country:
United States
Status:
Recruiting
Contact:
Last name:
Behnaz Agahian
Phone:
650-498-0623
Email:
behnaza@stanford.edu
Investigator:
Last name:
Nam Bui, M.D.
Email:
Principal Investigator
Investigator:
Last name:
Pejman Ghanouni, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Kristen Ganjoo, M.D.
Email:
Sub-Investigator
Start date:
August 15, 2023
Completion date:
February 1, 2028
Lead sponsor:
Agency:
Stanford University
Agency class:
Other
Collaborator:
Agency:
SpringWorks Therapeutics, Inc.
Agency class:
Industry
Source:
Stanford University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05949099
