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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
53
nirogacestat oral tablet
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States
Objective Response Rate (ORR)
The percentage of participants with complete response (CR) + partial response (PR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
Time frame: 2.5 years
Progression Free Survival at 6 Months (PFS-6)
The number of participants without progression according to RECIST v1.1 or death at 6 months.
Time frame: First day of cycle 7 (approximately 6 months after the first dose of study treatment). Each cycle is 28 days.
Overall Survival at Year 2
The number of participants who have not died of any cause by Year 2.
Time frame: 2 years after first dose of study treatment
Duration of Response
The time from response (Complete Response \[CR\] + Partial Response \[PR\] using RECIST v.1.) to disease progression and/or death, in participants with CR or PR.
Time frame: 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).
Change From Baseline at Cycle 2 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score.
Participant reported ovarian cancer symptoms as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). The FOSI is an 8-question evaluation scored on a Likert scale of 0-4 from not at all to very much. Metrics assessed include lack of energy, vomiting, pain, nausea, swelling in stomach area, concern condition will get worse, quality of life assessment and stomach cramps. Higher score means worse outcome. The responses to the statements except for statement 7 (I am content with the quality of my life right now) were reversed and the sum of non-missing responses is calculated. The FOSI score is the sum multiplied by 8, then divided by the number of responded statements. The FOSI score was missing if a participants had 5 or more missing values in the 8 individual symptom scores at a visit.
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UCLA-JCCC Dept. of OBGYN - Women's Health Clinical Research Unit
Los Angeles, California, United States
AdventHealth Orlando
Orlando, Florida, United States
Orlando Health Cancer Institute
Orlando, Florida, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
Women's Cancer Care
Covington, Louisiana, United States
Greater Baltimore Medical Center
Baltimore, Maryland, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
David C. Pratt Cancer Center
St Louis, Missouri, United States
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, United States
...and 11 more locations
Time frame: Baseline and at Cycle 2 Day 1 (cycle length is 28 days).
Change From Baseline at Cycle 3 Day 1 Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
Participant reported ovarian cancer symptoms as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). The FOSI is an 8-question evaluation scored on a Likert scale of 0-4 from not at all to very much. Metrics assessed include lack of energy, vomiting, pain, nausea, swelling in stomach area, concern condition will get worse, quality of life assessment and stomach cramps. Higher score means worse outcome. The responses to the statements except for statement 7 (I am content with the quality of my life right now) were reversed and the sum of non-missing responses is calculated. The FOSI score is the sum multiplied by 8, then divided by the number of responded statements. The FOSI score was missing if a participants had 5 or more missing values in the 8 individual symptom scores at a visit.
Time frame: Baseline and at Cycle 3 Day 1 (cycle length is 28 days).
Change From Baseline at Cycle 4 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
Participant reported ovarian cancer symptoms as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). The FOSI is an 8-question evaluation scored on a Likert scale of 0-4 from not at all to very much. Metrics assessed include lack of energy, vomiting, pain, nausea, swelling in stomach area, concern condition will get worse, quality of life assessment and stomach cramps. Higher score means worse outcome. The responses to the statements except for statement 7 (I am content with the quality of my life right now) were reversed and the sum of non-missing responses is calculated. The FOSI score is the sum multiplied by 8, then divided by the number of responded statements. The FOSI score was missing if a participants had 5 or more missing values in the 8 individual symptom scores at a visit.
Time frame: Baseline and at Cycle 4 Day 1 (cycle length is 28 days).
Change From Baseline at Cycle 5 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
Participant reported ovarian cancer symptoms as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). The FOSI is an 8-question evaluation scored on a Likert scale of 0-4 from not at all to very much. Metrics assessed include lack of energy, vomiting, pain, nausea, swelling in stomach area, concern condition will get worse, quality of life assessment and stomach cramps. Higher score means worse outcome. The responses to the statements except for statement 7 (I am content with the quality of my life right now) were reversed and the sum of non-missing responses is calculated. The FOSI score is the sum multiplied by 8, then divided by the number of responded statements. The FOSI score was missing if a participants had 5 or more missing values in the 8 individual symptom scores at a visit.
Time frame: Baseline and at Cycle 5 Day 1 (cycle length is 28 days).
Change From Baseline at End of Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
Participant reported ovarian cancer symptoms as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). The FOSI is an 8-question evaluation scored on a Likert scale of 0-4 from not at all to very much. Metrics assessed include lack of energy, vomiting, pain, nausea, swelling in stomach area, concern condition will get worse, quality of life assessment and stomach cramps. Higher score means worse outcome. The responses to the statements except for statement 7 (I am content with the quality of my life right now) were reversed and the sum of non-missing responses is calculated. The FOSI score is the sum multiplied by 8, then divided by the number of responded statements. The FOSI score was missing if a participants had 5 or more missing values in the 8 individual symptom scores at a visit.
Time frame: Baseline and at end of treatment (estimated to be an average of 5.5 months [minimum of 0 month and maximum of 33 months]).
Change From Baseline at Safety Follow-up in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score
Participant reported ovarian cancer symptoms as measured by Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI). The FOSI is an 8-question evaluation scored on a Likert scale of 0-4 from not at all to very much. Metrics assessed include lack of energy, vomiting, pain, nausea, swelling in stomach area, concern condition will get worse, quality of life assessment and stomach cramps. Higher score means worse outcome. The responses to the statements except for statement 7 (I am content with the quality of my life right now) were reversed and the sum of non-missing responses is calculated. The FOSI score is the sum multiplied by 8, then divided by the number of responded statements. The FOSI score was missing if a participants had 5 or more missing values in the 8 individual symptom scores at a visit.
Time frame: Baseline and at safety follow-up (up to a maximum of 34 months).