Nirogacestat in Ovarian Granulosa Cell Tumors

Ovarian Cancer Clinical Trial

Official title:

A Phase 2 Trial of Nirogacestat in Patients With Recurrent Ovarian Granulosa Cell Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05348356
• Other study ID #: NIR-OGT-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 30, 2022
• Est. completion date: December 2027

Study information

• Verified date: November 2023
• Source: SpringWorks Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 53
• Est. completion date: December 2027
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Ovarian Cancer
• Ovarian Granulosa Cell Tumor

Intervention

Drug:
• Nirogacestat
nirogacestat oral tablet

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Poland	Maria Sklodowska-Curie Bialystok Oncology Center	Bialystok
Poland	Jagiellonian Innovation Centre Clinical Research Centre	Kraków
Poland	University Teaching Hospital Poznan, Department of Oncological Gynaecology	Poznan
Poland	Maria Sklodowska-Curie National Institute of Oncology-National Research Institute, Clinic of Oncological Gynecology	Warsaw
United States	University of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Women's Cancer Care	Covington	Louisiana
United States	Women's Cancer Center at Kettering	Kettering	Ohio
United States	UCLA-JCCC Dept. of OBGYN - Women's Health Clinical Research Unit	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Froedtert and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Institute	New York	New York
United States	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	AdventHealth Orlando	Orlando	Florida
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	David C. Pratt Cancer Center	Saint Louis	Missouri
United States	UW/Fred Hutch Cancer Center	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
SpringWorks Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	The proportion of participants with complete response (CR) + partial response (PR) assessed using RECIST v1.1 criteria.	2.5 years
Secondary	Progression Free Survival at 6 months (PFS-6)	The number of participants without progression according to RECIST v1.1 or death at 6 months.	First day of cycle 7 (approximately 6 months after the first dose of study treatment). Each cycle is 28 days.
Secondary	Overall Survival	The number of participants who have not died of any cause.	2 years after first dose of study treatment
Secondary	Participant reported ovarian cancer symptoms	Change from baseline as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI).	At each study visit until study completion (estimated to be an average of 2.5 years)
Secondary	Duration of Response	The time from response (CR + PR using RECIST v.1.) to disease progression and/or death	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).