A Phase II Multicenter Study of AMG 386 and Abiraterone in Metastatic Castration Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
Background:
- Advanced prostate cancer is treated with surgery or drugs that lower the levels of androgens (male hormones) in the body. However, some cancers become resistant to this treatment. These types of cancers are known as castration-resistant prostate cancers.
- Interfering with the growth of blood vessels that feed tumors can slow prostate cancer growth. Trebananib (AMG 386), a new anticancer drug, targets the blood vessels that feed tumors. It has been tested for different types of cancer, but not for prostate cancer. Researchers want to see if AMG 386 can slow disease progression in men with castration-resistant prostate cancer. AMG 386 will be given with abiraterone and prednisone, two drugs that are also used to treat advanced prostate cancer.
Objectives:
- To test the safety and effectiveness of AMG 386 with abiraterone for castration-resistant prostate cancer.
Eligibility:
- Men at least 18 years of age with castration-resistant prostate cancer.
Design:
- Participants will be screened with a physical exam, medical history, and imaging studies. Blood and urine samples will also be collected.
- Participants will be separated into two groups.
- The first group will have AMG 386 once per week for a total of four doses during a 28-day cycle. They will also take abiraterone once a day and prednisone twice a day, every day of the cycle.
- The second group will not have AMG 386. They will take abiraterone once a day and prednisone twice a day, every day of the 28-day cycle.
- Treatment will be monitored with frequent blood tests and imaging studies.
- Participants will continue to take the study drugs as long as the disease does not progress and there are no severe side effects.
详细描述
Background:
- Inhibition of angiogenesis, either as a stand-alone approach or in combination with chemotherapy, has demonstrable antitumor efficacy against castration-resistant prostate cancer (CRPC) and there are several antiangiogenic agents that are now in clinical trials in this population of patients.
- AMG 386 is a novel peptide-Fc fusion protein. The molecule is a non-glycosylated homodimer engineered by fusing an Immunoglobulin gamma-1 heavy chain constant region, partial (IgG1 Fc) domain to 4 copies of an anti-angiopoietin 2 (Ang2) peptide. AMG 386 sequesters Ang1 and Ang2, thereby preventing their interaction with Tie2 and inhibiting tumor endothelial cell (EC) proliferation and tumor growth.
- Abiraterone acetate is a small molecule that irreversibly inhibits Cytochrome P450 17A1 (CYP17), a rate-limiting enzyme in androgen biosynthesis, to block residual androgen synthesis in the adrenal gland and tumor cells.
- Previous studies have demonstrated that in vivo alterations of testosterone levels regulate the expression of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and angiopoietin family members. Dual targeting of the androgen and angiogenic axis represents a novel approach as a potential targeted therapy for patients with metastatic castration-resistant prostate cancer (CRPC).
Objectives:
-To estimate the treatment effect as measured by progression free survival (PFS) in patients treated with AMG 386 plus abiraterone/prednisone relative to abiraterone/prednisone alone.
Eligibility:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- Male
- 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
Abiraterone, Prednisone and AMG
Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG)
干预措施: AMG 386 (Drug)
Abiraterone, Prednisone and AMG
Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG)
干预措施: Abiraterone (Drug)
Abiraterone, Prednisone and AMG
Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG)
干预措施: Prednisone (Drug)
Abiraterone and Prednisone only
Abiraterone and prednisone only
干预措施: Abiraterone (Drug)
Abiraterone and Prednisone only
Abiraterone and prednisone only
干预措施: Prednisone (Drug)
Run in
Dose escalation phase to determine MTD of AMG
干预措施: AMG 386 (Drug)
Run in
Dose escalation phase to determine MTD of AMG
干预措施: Abiraterone (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Median potential follow-up of 50.3 months
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first. Clinical progression is assessed by the Response Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
次要结局
- Radiographic Progression Free Survival(Median potential follow-up of 50.3 months)
- Overall Survival(Time between the first day of treatment to the day of death, approximately 50.3 months.)
- Count of Participants With Serious and Non-serious Adverse Events(Date treatment consent signed to date off study, approximately 65 months and 7 days)
研究者
Ravi A. Madan, M.D.
Principal Investigator
National Cancer Institute (NCI)