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Completed

NCT Number: NCT05348356

Nirogacestat in Ovarian Granulosa Cell Tumors

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.

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Key information

Conditions

Ovarian Granulosa-Stromal Tumor Adnexal Diseases Endocrine Gland Neoplasms Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Granulosa cell tumor of the ovary Neoplasms Neoplasms by Site Ovarian Cancer Ovarian Diseases Ovarian Granulosa Cell Tumor Ovarian Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Cross Cancer Institute, Edmonton, Alberta, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Nirogacestat

Drug

nirogacestat oral tablet

Other names: PF-03084014

Primary outcomes

  1. Objective Response Rate (ORR)

    Time frame: 2.5 years

    The percentage of participants with complete response (CR) + partial response (PR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

Secondary outcomes

  1. Progression Free Survival at 6 Months (PFS-6)

    Time frame: 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.

  2. Overall Survival at Year 2

    Time frame: 2 years after first dose of study treatment

    The number of participants who have not died of any cause by Year 2.

  3. Duration of Response

    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).

    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.

  4. Change From Baseline at Cycle 2 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score.

    Time frame: Baseline and at Cycle 2 Day 1 (cycle length is 28 days).

    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.

  5. Change From Baseline at Cycle 3 Day 1 Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score

    Time frame: Baseline and at Cycle 3 Day 1 (cycle length is 28 days).

    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.

  6. Change From Baseline at Cycle 4 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score

    Time frame: Baseline and at Cycle 4 Day 1 (cycle length is 28 days).

    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.

  7. Change From Baseline at Cycle 5 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score

    Time frame: Baseline and at Cycle 5 Day 1 (cycle length is 28 days).

    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.

  8. Change From Baseline at End of Treatment in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score

    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]).

    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.

  9. Change From Baseline at Safety Follow-up in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score

    Time frame: Baseline and at safety follow-up (up to a maximum of 34 months).

    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.

Sponsors and collaborators

Lead sponsor

SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany

Industry

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Apr 27, 2022
Registry last updated
Aug 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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