Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Anti-Inflammatory Agents

Antineoplastic Agents

All Drugs and Chemicals

Prednisone

Trebananib

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Angiogenesis Inhibitors

Growth Inhibitors

Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG)

Dose escalation phase to determine MTD of AMG

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.

AMG 386

A 1,000 mg dose of abiraterone should be taken orally once daily

Abiraterone

Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.

Ravi A Madan, M.D.

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.

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.

AMG 386 and Abiraterone for Advanced Prostate Cancer

A Phase II Multicenter Study of AMG 386 and Abiraterone in Metastatic Castration Resistant Prostate Cancer

The MTD is defined as the highest dose studied for which the incidence of dose limiting toxicity was less than 33%.

DLTs are defined as any grade 3 or higher hematologic (excluding anemia) or non-hematologic toxicity considered to be possible related to AMG 386. Any treatment related adverse events that lead tor reduction of dose exposure of either agent (duration or dose) by \>50% in cycle 1 will be considered a DLT.

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).

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 is the time between the first day of treatment to the day of death.

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.

National Cancer Institute (NCI)

Principal Investigator

Dose escalation phase to determine MTD of AMG

AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg).

Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily

DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg

The randomized portion is 30 mg/kg.

DL 1 Run in - 15mg/kg

DL 2 Run in - 30mg/kg

Abiraterone and prednisone will be given with maximum tolerated dose (MTD) of Trebananib (AMG)

AMG 386: 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.

Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily

Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.

Abiraterone, Prednisone and AMG

Abiraterone and prednisone only

Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily

Prednisone: Prednisone should be taken orally either, at 5mg twice a day for each dose or 10 mg once a day a patients preference.

Abiraterone and Prednisone Only

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Not meeting definition for Hispanic or Latino

Mexican, Puerto Rican, Cuban, Central or So Amer.

Black or African American

White

Unknown

Race/Ethnicity, Customized

United States

Region of Enrollment

>4.0 mg/mL

<4.0 mg/mL

Prostatic Specific Antigen (PSA) reference range is 4.0 ng/mL

OnStudy Prostatic Specific Antigen (PSA)

Dr. Ravi Madan

Dose escalation phase to determine MTD of AMG AMG 386: AMG 386 dose will be calculated using the subjects actual body weight (Kg).

Abiraterone: A 1,000 mg dose of abiraterone should be taken orally once daily DL 1 AMG is 15 mg/kg DL 2 AMG is 30 mg/kg The randomized portion is 30 mg/kg.

One patient of the 9 (i.e., Run-in in Participant Flow) was not evaluable for responses as we previously defined through the document. Thus, it cannot be included in the PFS assessment. Patient came off the trial early for other reasons.

Progression Free Survival (PFS)

Radiographic Progression Free Survival

Overall Survival

Count of Participants With Serious and Non-serious Adverse Events

All participants who had at least one dose of Abiraterone, prednisone, and/or Trebananib (AMG 386).

Spots Global Cancer Trial Database for neoplasm,prostatic