AMG 386 and Abiraterone for Advanced Prostate Cancer
- 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. 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.
- To test the safety and effectiveness of AMG 386 with abiraterone for castration-resistant prostate cancer.
- Men at least 18 years of age with castration-resistant prostate cancer.
- 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.
Drug: AMG 386
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Multicenter Study of AMG 386 and Abiraterone in Metastatic Castration Resistant Prostate Cancer|
- 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.
- OS, safety and toxicity, androgen and angiogenesis signaling biomarker assessment and efficacy correlation, assess changes in angiogenesis markers and CTC's before and after agent administration.
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||February 2016|
|Estimated Primary Completion Date:||February 2016 (Final data collection date for primary outcome measure)|
Drug: AMG 386
- 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 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 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 VEGF, 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 CRPC.
-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.
-Patients with progressive, metastatic CRPC with radiographic evidence of progression after primary therapy (surgery or radiotherapy) and adequate androgen deprivation therapy.
- This is an open-label, randomized, phase II multicenter trial with a two-part design and a planned accrual of 88 patients.
- An initial run-in phase of AMG 386 will be conducted with 15mg/kg weekly escalating to 30mg/kg weekly to establish the MTD. The decision on declaration of a safe and tolerable dose during this run-in phase will lead to the second part of the study consisting of a randomized comparison of abiraterone/prednisone plus AMG 386 (at the established MTD) vs. abiraterone/prednisone alone.
- AMG 386 will be administered intravenously every week, on days 1, 8, 15 and 22 of each 28-day cycle. Abiraterone acetate will be self-administered once daily by mouth and prednisone will be self-administered by mouth either twice per day at 5 mg per dose or once per day at 10 mg per dose as the patient prefers.
|Contact: Guinevere Chun, R.N.||(301) email@example.com|
|Contact: William L Dahut, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|United States, Pennsylvania|
|Fox Chase Cancer Center||Recruiting|
|Philadelphia, Pennsylvania, United States, 19111|
|Principal Investigator:||William L Dahut, M.D.||National Cancer Institute (NCI)|