AMG 386 and Abiraterone for Advanced Prostate Cancer

NCT01553188 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 12007912-C-0079
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

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.

Conditions

Prostatic Neoplasms; Prostate Cancer; Neoplasm, Prostate; Neoplasm,Prostatic

Keywords

Anti-Angiogenesis; Ang 1; Ang 2; Peptide-Fc fusion protein; Small Molecule

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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).

  Median potential follow-up of 50.3 months

Secondary Outcomes (3)

• Radiographic Progression Free Survival

  Median potential follow-up of 50.3 months

• Overall Survival

  Time between the first day of treatment to the day of death, approximately 50.3 months.

• Count of Participants With Serious and Non-serious Adverse Events

  Date treatment consent signed to date off study, approximately 65 months and 7 days

Other Outcomes (2)

• Maximum Tolerated Dose (MTD)

  First 28 days of treatment

• Dose Limiting Toxicity (DLT)

  First 28 days of treatment

Study Arms (3)

Abiraterone, Prednisone and AMG

EXPERIMENTAL

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

Drug: AMG 386; Drug: Abiraterone; Drug: Prednisone

Abiraterone and Prednisone only

ACTIVE COMPARATOR

Abiraterone and prednisone only

Drug: Abiraterone; Drug: Prednisone

Run in

OTHER

Dose escalation phase to determine MTD of AMG

Drug: AMG 386; Drug: Abiraterone

Interventions

AMG 386 DRUG

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.

Also known as: Trebananib

Abiraterone, Prednisone and AMG; Run in

Abiraterone DRUG

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

Also known as: Zytiga

Abiraterone and Prednisone only; Abiraterone, Prednisone and AMG; Run in

Prednisone DRUG

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

Also known as: Deltasone

Abiraterone and Prednisone only; Abiraterone, Prednisone and AMG

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have metastatic, progressive, castrate-resistant prostate cancer (CRPC) with radiographic evidence of disease that has continued to progress radiographically or biochemically (rising prostatic specific antigen (PSA) levels on successive measurements) despite adequate androgen-deprivation therapy. If patients had been on flutamide, disease progression is documented 4 weeks or more after withdrawal. For patients on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal. Flutamide, nilutamide and bicalutamide disease progression requirements only apply to patients who have been on these drugs for at least the prior 6 months.
• Histopathological confirmation of prostate cancer by the Laboratory of Pathology of the National Cancer Institute (NCI) or Walter Reed National Military Medical Center prior to entering this study. Patients enrolled at participating sites may have histopathological confirmation at the enrolling center prior to entering the study. Patients whose pathology specimens are no longer available may be enrolled if the patient has a clinical course that is consistent with prostate cancer and available documentation from an outside pathology laboratory of the diagnosis. All efforts should be made to have the material forwarded to the research team for use in correlative studies in cases where original tissue blocks or archival biopsy material is available.
• Patients must have metastatic disease, defined as at least one lesion on bone scan or at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam.
• Patients participating in the study must have Metastatic Castration-Resistant Prostate Cancer (mCRPC).
• Patients who have received docetaxel plus androgen deprivation therapy (ADT) for metastatic castrate sensitive prostate cancer are eligible for the study. (Patients may enroll as long as they did not have progressive disease while on docetaxel and are 6 months removed from treatment, with all treatment related toxicities resolving to at least grade 1.)
• Patients may not have had more than 7 days of treatment with ketoconazole by mouth in the past 6 months.
• Males greater than or equal to 18 years of age. Because no dosing or adverse event data are currently available on the use AMG 386 in combination with abiraterone in patients \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 for run-in phase; ECOG less than or equal to 1 for randomized phase.
• Life expectancy of \> 3 months for the run in phase and \> 6 months for the randomized phase.
• Adequate bone marrow, hepatic, and renal function with:
• Leukocytes greater than or equal to 3000/mu L
• Absolute neutrophil count (ANC) greater than or equal to 1500/mu L
• Platelets greater than or equal to 100000/mu L
• Total bilirubin less than or equal to 1.5 times institutional upper limits of normal
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase(SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase(SGPT) less than or equal to 2.5 times institutional upper limits of normal

You may not qualify if:

• Patients who have had chemotherapy for metastatic castration-resistant prostate cancer.
• History or presence of known central nervous system metastases.
• History of venous or arterial thromboembolism within 12 months prior to enrollment/randomization.
• History of clinically significant bleeding within 6 months of enrollment/randomization.
• Currently or previously treated with AMG 386, or other molecules that primarily inhibit the angiopoietins or Tie2 receptor.
• Clinically significant cardiovascular disease within 12 months prior to enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stent.
• Major surgery within 28 days prior to enrollment or still recovering from prior surgery.
• Minor surgical procedures, placement of tunneled central venous access device within 3 days prior to randomization/enrollment.
• Treatment within 30 days prior to enrollment with the following: cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, methotrexate, azathioprine, rapamycin, and targeted immune modulators such as abatacept (CTLA-4-Ig), adalimumab,
• alefacept, anakinra, belatacept (LEA29Y), efalizumab, etanercept, infliximab, or rituximab.
• Patients who have had large field radiotherapy must wait 2 weeks prior to entering the study.
• Non-healing wound, ulcer (including gastrointestinal), or fracture.
• Contraindication to steroid use or history of allergic reactions attributable to the study compounds.
• History of allergic reactions to bacterially-produced proteins.
• Previously diagnosed with another malignancy, within the past two years with the exception of non-melanoma skin cancers or non-invasive bladder cancer.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (3)

• Goktas S, Crawford ED. Optimal hormonal therapy for advanced prostatic carcinoma. Semin Oncol. 1999 Apr;26(2):162-73.

  PMID: 10597727 BACKGROUND

• Gulley J, Dahut WL. Chemotherapy for prostate cancer: finally an advance! Am J Ther. 2004 Jul-Aug;11(4):288-94. doi: 10.1097/01.mjt.0000133582.68709.e3.

  PMID: 15266221 BACKGROUND

• Berthold DR, Sternberg CN, Tannock IF. Management of advanced prostate cancer after first-line chemotherapy. J Clin Oncol. 2005 Nov 10;23(32):8247-52. doi: 10.1200/JCO.2005.03.1435.

  PMID: 16278480 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

trebananib; abiraterone; Abiraterone Acetate; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Results Point of Contact

• Title: Dr. Ravi Madan
• Organization: National Cancer Institute

madanr@mail.nih.gov

301-480-7168

Study Officials

• Ravi A Madan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 10, 2012
• First Posted: March 14, 2012
• Study Start: February 8, 2012
• Primary Completion: April 20, 2017
• Study Completion: July 1, 2018
• Last Updated: March 5, 2019
• Results First Posted: October 16, 2018

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)