A Phase 2 Study of ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Cohort 1 - Progression-free Survival (PFS)
研究概览
简要总结
Background:
The new drug ONC201 have been shown to kill breast cancer and endometrial cancer cells in the laboratory. The exact mechanism of action is not completely clear yet, but the ONC201 destroys the mitochondria inside the cells. Blocking mitochondrial activity may kill tumor cells, which would shrink tumors. Researchers want to see if ONC201 helps shrink tumors of certain breast or endometrial cancers and if that effect is maintained.
Objective:
To see if ONC201 shrinks tumors with a lasting effect.
Eligibility:
Adults ages 18 and older who have metastatic breast cancer (hormone-positive or triple-negative) or metastatic endometrial cancers.
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Heart, blood, and urine tests
- Computed tomography (CT) and bone scans
- Review of medical report and tumor sample
- Participants will have a tumor biopsy before starting treatment and after 5 weeks taking the study drug. A scan or ultrasound may be used to guide the biopsy. Patients will receive local anesthetic and a needle will remove a small piece of tumor.
- The study will be done in 28-day cycles. Every day 1 of each cycle participants will repeat most screening tests, will be seen by the physician and receive a supply of the study drug.
- Participants will take the study drug by mouth once every 7 days. They will keep a diary of when they take the drug and any side effects. During cycle 1, participants will get weekly calls to discuss their health and symptoms. Images will be repeated every 2 cycles to evaluate response to the treatment.
详细描述
Background:
- Advanced breast cancer and endometrial cancer have limited treatment options. Current treatments provide a modest improvement in progression free survival, but no treatments improve survival.
- ONC201 is the founding member of a novel class of anticancer drugs called imipridones. The exact mechanism of ONC201 is unknown at this time, but preclinical data suggests that it causes global downregulation of mitochondrial genes leading to mitochondrial damage and ultimately non-apoptotic cell death.
- Preclinical studies have demonstrated that ONC201 selectively kills various cancer cells, including breast cancer cells (hormone-receptor positive cell lines, human epidermal growth factor receptor 2 (HER2+) cell line as well as triple negative breast cancer cell lines) and endometrial cancer cells, while having little effect on normal cells.
- An on-going phase I study of ONC201 has demonstrated clinical benefit in some solid tumors, including endometrial cancer.
Objectives:
- Cohort 1: To determine the progression free survival (PFS) at 8 months of ONC201 in metastatic hormone receptor positive breast cancer (HR+BC)
- Cohort 2: To determine the overall response rate (ORR) of ONC201 in metastatic triple negative breast cancer (TNBC)
- Cohort 3: To determine the overall response rate (ORR) of ONC201 in advanced endometrial cancer (EC)
Eligibility:
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
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1-ONC201 in Recurrent/Refractory Metastatic Breast Cancer and Advanced Endometrial Carcinoma
Single arm divided in three cohorts, each cohort with a different type of metastatic disease: estrogen receptor (ER) + breast cancer, triple negative breast cancer, and endometrial cancer
干预措施: ONC201 (Drug)
结局指标
主要结局
Cohort 1 - Progression-free Survival (PFS)
时间窗: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
PFS in participants with refractory, metastatic hormone receptor positive breast cancer. PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions. And the appearance of one or more new lesions.
Cohort 2 - Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST)
时间窗: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
Overall response (Complete response (CR) + Partial Response (PR) of ONC201 in participants with metastatic triple negative breast cancer was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions.
Cohort 3 - Overall Response Rate (ORR) (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST)
时间窗: Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).
Overall response (Complete response (CR) + Partial Response (PR) of ONC201 in participants with advanced or metastatic endometrial cancer was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions.
次要结局
- Cohorts 2 and 3 - Progression-free Survival (PFS)(Every 8 weeks, while on treatment, up to 3 months)
- Number of Serious and Non-serious Adverse Events Grade ≥1 in Cohorts 1, 2, and 3(Date treatment consent signed to date off study, approximately 13 months and 28 days for cohort 1, 11 months and 12 days for cohort 2, and 34 months and 29 days for cohort 3.)
- Cohort 1 - Overall Response Rate (Complete Response (CR) + Partial Response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST)(Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).)
- Number of Participants in Cohorts 1, 2, and 3 With Clinical Benefit(Every 8 weeks, while on the Trial. Participants were followed for an average of 8-10 weeks (up to 16 weeks).)
研究者
Stanley Lipkowitz, MD, PhD
Principal Investigator
National Cancer Institute (NCI)