A Phase 2 Trial of Nirogacestat in Patients With Recurrent Ovarian Granulosa Cell Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 42
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Nirogacestat Open-Label
Nirogacestat 150 mg by mouth, twice daily
Nirogacestat oral tablet: Nirogacestat tablet
干预措施: Nirogacestat (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 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.
次要结局
- Overall Survival(2 years after first dose of study treatment)
- 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.)
- Participant reported ovarian cancer symptoms(At each study visit until study completion (estimated to be an average of 2.5 years))
- 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).)
- 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.)
- Overall Survival at Year 2(2 years after first dose of study treatment)
- Change From Baseline at Cycle 2 Day 1 in the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI) Score.(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(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(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(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(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(Baseline and at safety follow-up (up to a maximum of 34 months).)