AMG 386 and Abiraterone for Advanced Prostate Cancer

Phase 2

Completed

Conditions: Prostatic Neoplasms
Neoplasm, Prostate
Prostate Cancer
Neoplasm,Prostatic

Interventions: Drug: AMG 386
Drug: Abiraterone
Drug: Prednisone

Registration Number: NCT01553188

Lead Sponsor: National Cancer Institute (NCI)

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 36

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Run in	AMG 386	Dose escalation phase to determine MTD of AMG
Abiraterone, Prednisone and AMG	AMG 386	Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG)
Abiraterone and Prednisone only	Abiraterone	Abiraterone and prednisone only
Abiraterone, Prednisone and AMG	Prednisone	Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG)
Abiraterone, Prednisone and AMG	Abiraterone	Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG)
Abiraterone and Prednisone only	Prednisone	Abiraterone and prednisone only
Run in	Abiraterone	Dose escalation phase to determine MTD of AMG

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	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).

Secondary Outcome Measures

Name	Time	Method
Radiographic Progression Free Survival	Median potential follow-up of 50.3 months	Radiographic progression free survival is defined as the duration of time from start of treatment to time of radiographic progression by computed tomography (CT) scan (or magnetic resonance imaging (MRI)) or bone scan. Progression is a minimum of two new lesions observed on bone scan. The minimum size for a measurable lesion on CY and MRI should be twice the slice thickness based on the assumption that CT slice thickness is 500 or less.
Overall Survival	Time between the first day of treatment to the day of death, approximately 50.3 months.	Overall Survival is the time between the first day of treatment to the day of death.
Count of Participants With Serious and Non-serious Adverse Events	Date treatment consent signed to date off study, approximately 65 months and 7 days	Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Trial Locations

Locations (2): National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸
Bethesda, Maryland, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States