Ignite Creation Date:
2024-05-06 @ 12:20 AM
Last Modification Date:
2024-10-26 @ 10:48 AM
Study NCT ID:
NCT01553188
Status:
COMPLETED
Last Update Posted:
2019-03-05
First Post:
2012-03-10
Brief Title:
AMG 386 and Abiraterone for Advanced Prostate Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase II Multicenter Study of AMG 386 and Abiraterone in Metastatic Castration Resistant Prostate Cancer
Status:
COMPLETED
Status Verified Date:
2019-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 abirateroneprednisone relative to abirateroneprednisone 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 15mgkg weekly escalating to 30mgkg 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 abirateroneprednisone plus AMG 386 at the established maximum tolerated dose MTD vs abirateroneprednisone 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
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 abirateroneprednisone relative to abirateroneprednisone 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 15mgkg weekly escalating to 30mgkg 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 abirateroneprednisone plus AMG 386 at the established maximum tolerated dose MTD vs abirateroneprednisone 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 12-C-0079 | None | None | None |