Nirogacestat in Ovarian Granulosa Cell Tumors

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Ovarian Granulosa-Stromal Tumor, Ovarian Granulosa Cell Tumor, Ovarian Cancer

Intervention / Treatment
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* Drug: Nirogacestat


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nirogacestat Open-Label<br>All participants will receive open-label nirogacestat | Drug: Nirogacestat<br>* nirogacestat oral tablet<br>* Other names: PF-03084014;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| Overall Survival | The number of participants who have not died of any cause. | 2 years after first dose of study treatment | 
| 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) | 
| 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). |