Clinical trial NCT05348356: Nirogacestat in Ovarian Granulosa Cell Tumors
Official title: A Phase 2 Trial of Nirogacestat in Patients With Recurrent Ovarian Granulosa Cell Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Ovarian Granulosa-Stromal Tumor
Ovarian Granulosa Cell Tumor
Ovarian Cancer
Lead sponsor: SpringWorks Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-27
Enrollment: 53
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase 2 clinical trial will study the effectiveness of nirogacestat in ovarian granulosa cell tumors (OvGCTs). Nirogacestat is a gamma secretase inhibitor (GSI) which is hypothesized to decrease the growth and activity of ovarian granulosa tumors.

Detailed description: Ovarian granulosa cell tumors (OvGCTs) represent 5-7% of all ovarian cancers (\~1.5 to 2k newly diagnosed patients/year in the United States) and are the most common subtype of ovarian sex cord tumors (70%). Treatment of granulosa cell tumors with nirogacestat is expected to inhibit Notch-induced granulosa cell proliferation.

This is a multi-center, single-arm, Phase 2 open label treatment study to determine the efficacy, safety, tolerability, and pharmacokinetics of nirogacestat in adult participants with relapsed/refractory OvGCT. The participants will continue treatment until disease progression as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (unless the participants meet criteria for continued treatment) or unacceptable toxicity.

Eligibility criteria: Key Inclusion Criteria:

* Has histologically confirmed recurrent adult-type granulosa cell tumor of the ovary prior to first dose of study treatment
* Have documented radiological evidence of relapse after at least one systemic therapy that is not amenable to surgery, or radiation and have measurable disease by RECIST v1.1 criteria
* Have adequate bone marrow, renal and hepatic function as defined by screening visit laboratory values

Key Exclusion Criteria:

* Has signs of bowel obstruction requiring parenteral nutrition, malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of nirogacestat
* Has had a major cardiac or thrombo-embolic event within 6 months of signing informed consent
* Has abnormal QT interval at Screening, or has congenital or acquired long QT syndrome or a history of additional risk factors for Torsades de Pointes
* Has current or chronic history of liver disease or known hepatic or biliary abnormalities
* Has received bevacizumab treatment or other monoclonal antibody therapy with targeted anti-angiogenic activity for OvGCT within 28 days (or 5 half-lives, whichever is shorter) prior to the first dose of study treatment;
* Has received treatment for OvGCT including but not limited to the following within 28 days (or 5 half-lives, whichever is longer) prior to the first dose of study treatment: hormonal therapy, chemotherapy, immunotherapy, targeted therapy or any investigational treatment

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 2.5 years
Secondary outcomes:
measure: Progression Free Survival at 6 months (PFS-6)
timeFrame: First day of cycle 7 (approximately 6 months after the first dose of study treatment). Each cycle is 28 days.
measure: Overall Survival
timeFrame: 2 years after first dose of study treatment
measure: Participant reported ovarian cancer symptoms
timeFrame: At each study visit until study completion (estimated to be an average of 2.5 years)
measure: Duration of Response
timeFrame: First day of every other cycle (each cycle is 28 days) for the first year, and then every 3 cycles thereafter until study completion (estimated to be an average of 2.5 years).
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA-JCCC Dept. of OBGYN - Women's Health Clinical Research Unit
state: California
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Covington
country: United States
facility: Women's Cancer Care
state: Louisiana
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center
state: New Mexico
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Institute
state: New York
city: Kettering
country: United States
facility: Women's Cancer Center at Kettering
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Seattle
country: United States
facility: UW/Fred Hutch Cancer Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert and Medical College of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Białystok
country: Poland
facility: Maria Sklodowska-Curie Bialystok Oncology Center
city: Kraków
country: Poland
facility: Jagiellonian Innovation Centre Clinical Research Centre
city: Poznań
country: Poland
facility: University Teaching Hospital Poznan, Department of Oncological Gynaecology
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie National Institute of Oncology-National Research Institute, Clinic of Oncological Gynecology
Study officials:
References: