Nirogacestat in Ovarian Granulosa Cell Tumors
- Conditions
- Ovarian CancerOvarian Granulosa-Stromal TumorOvarian Granulosa Cell Tumor
- Interventions
- Registration Number
- NCT05348356
- Lead Sponsor
- SpringWorks Therapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 53
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Nirogacestat Open-Label Nirogacestat All participants will receive open-label nirogacestat
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) 2.5 years The proportion of participants with complete response (CR) + partial response (PR) assessed using RECIST v1.1 criteria.
- Secondary Outcome Measures
Name Time Method Overall Survival 2 years after first dose of study treatment The number of participants who have not died of any cause.
Progression Free Survival at 6 months (PFS-6) First day of cycle 7 (approximately 6 months after the first dose of study treatment). Each cycle is 28 days. The number of participants without progression according to RECIST v1.1 or death at 6 months.
Duration of Response 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). The time from response (CR + PR using RECIST v.1.) to disease progression and/or death
Participant reported ovarian cancer symptoms At each study visit until study completion (estimated to be an average of 2.5 years) Change from baseline as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI).
Trial Locations
- Locations (21)
UCLA-JCCC Dept. of OBGYN - Women's Health Clinical Research Unit
🇺🇸Los Angeles, California, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
OU Health Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Froedtert and Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Women's Cancer Care
🇺🇸Covington, Louisiana, United States
Greater Baltimore Medical Center
🇺🇸Baltimore, Maryland, United States
David C. Pratt Cancer Center
🇺🇸Saint Louis, Missouri, United States
University of New Mexico Comprehensive Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Institute
🇺🇸New York, New York, United States
Women's Cancer Center at Kettering
🇺🇸Kettering, Ohio, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Maria Sklodowska-Curie Bialystok Oncology Center
🇵🇱Białystok, Poland
UW/Fred Hutch Cancer Center
🇺🇸Seattle, Washington, United States
Jagiellonian Innovation Centre Clinical Research Centre
🇵🇱Kraków, Poland
Maria Sklodowska-Curie National Institute of Oncology-National Research Institute, Clinic of Oncological Gynecology
🇵🇱Warsaw, Poland
University Teaching Hospital Poznan, Department of Oncological Gynaecology
🇵🇱Poznań, Poland
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States