AMG 386 and Abiraterone for Advanced Prostate Cancer
Condition: Prostatic Neoplasms; Prostate Cancer; Neoplasm, Prostate; Neoplasm,Prostatic
MeSH terms: Prostatic Neoplasms; Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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:

      -Patients with progressive, metastatic CRPC with radiographic evidence of progression after
      primary therapy (surgery or radiotherapy) and adequate androgen deprivation therapy.

      Design:

        -  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 maximum
           tolerated dose (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.
    

Intervention name(s): AMG 386; Abiraterone; Prednisone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): AMG 386 dose will be calculated using the subjects actual body weight (Kg). Supplied in 240 mg v will be administered as an intravenous (IV) infusion using an intravenous infusion pump given over a 60-minute period.; A 1,000 mg dose of abiraterone should be taken orally once daily; Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.
Other intervention name(s): Trebananib; Zytiga; Deltasone
Intervention MeSH terms: Prednisone; Trebananib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Anti-Angiogenesis; Ang 1; Ang 2; Peptide-Fc fusion protein; Small Molecule