Nirogacestat in Ovarian Granulosa Cell Tumors
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| ClinicalTrials.gov Identifier: NCT05348356 |
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Recruitment Status :
Active, not recruiting
First Posted : April 27, 2022
Last Update Posted : November 22, 2023
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Sponsor:
SpringWorks Therapeutics, Inc.
Information provided by (Responsible Party):
SpringWorks Therapeutics, Inc.
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ovarian Granulosa-Stromal Tumor Ovarian Granulosa Cell Tumor Ovarian Cancer | Drug: Nirogacestat | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 53 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2 Trial of Nirogacestat in Patients With Recurrent Ovarian Granulosa Cell Tumors |
| Actual Study Start Date : | August 30, 2022 |
| Estimated Primary Completion Date : | July 2026 |
| Estimated Study Completion Date : | December 2027 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Ovarian cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: Nirogacestat Open-Label
All participants will receive open-label nirogacestat
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Drug: Nirogacestat
nirogacestat oral tablet
Other Name: PF-03084014 |
Primary Outcome Measures :
- Objective Response Rate (ORR) [ Time Frame: 2.5 years ]The proportion of participants with complete response (CR) + partial response (PR) assessed using RECIST v1.1 criteria.
Secondary Outcome Measures :
- 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.
- Overall Survival [ Time Frame: 2 years after first dose of study treatment ]The number of participants who have not died of any cause.
- Participant reported ovarian cancer symptoms [ Time Frame: 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).
- 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 (CR + PR using RECIST v.1.) to disease progression and/or death
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05348356
Locations
Show 21 study locations
Sponsors and Collaborators
SpringWorks Therapeutics, Inc.
| Responsible Party: | SpringWorks Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT05348356 |
| Other Study ID Numbers: |
NIR-OGT-201 |
| First Posted: | April 27, 2022 Key Record Dates |
| Last Update Posted: | November 22, 2023 |
| Last Verified: | November 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | SpringWorks Therapeutics is committed to data transparency and sharing data to further research while maintaining the privacy and confidentiality of research participants. Pertinent patient-level data from completed clinical trials will be made available by SpringWorks to qualified researchers upon approval of reasonable requests following de-identification/anonymization pursuant to applicable law. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Neoplasms Granulosa Cell Tumor Ovarian Neoplasms Endocrine Gland Neoplasms Neoplasms by Site Ovarian Diseases Adnexal Diseases Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Genital Neoplasms, Female |
Urogenital Neoplasms Genital Diseases Endocrine System Diseases Gonadal Disorders Sex Cord-Gonadal Stromal Tumors Neoplasms, Gonadal Tissue Neoplasms by Histologic Type Nirogacestat Gamma Secretase Inhibitors and Modulators Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |