3-arm Study of Abiraterone Acetate Alone, Abiraterone Acetate Plus Degarelix, a GnRH Antagonist, and Degarelix Alone for Patients With Prostate Cancer With a Rising PSA or a Rising PSA and Nodal Disease Following Definitive Radical Prostatectomy

NCT01751451 | Completed Phase 2 Results

• 1 other identifier: 12-187
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 16

Brief Summary

In April 2011, the United States Food and Drug Administration (FDA) approved the oral drug abiraterone acetate (Zytiga ®) in combination with prednisone (a steroid) to treat patients with metastatic castration-resistant prostate cancer who have received prior docetaxel (chemotherapy). In December 2012, the FDA approved Zytiga ® in combination with prednisone to treat patients with metastatic castration-resistant prostate cancer who have not received prior chemotherapy. Degarelix (Firmagon ®), a testosterone lowering agent given as a monthly injection, is FDA approved for the treatment of patients with advanced prostate cancer. The purpose of this study is to evaluate abiraterone acetate and prednisone in combination with degarelix as a possible treatment for PSA recurrent prostate cancer as compared to abiraterone acetate alone and degarelix alone. This will be the first time these drugs will be used together.

Conditions

Prostate Cancer

Keywords

ABIRATERONE ACETATE (CB 7630); DEGARELIX; PREDNISONE; 12-187

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS)

  defined as an undetectable PSA (using a routine non-ultrasensitive PSA assay) with non-castrate level of testosterone (\>150 ng/dL) at 18 months from the time of treatment initiation (PSA0).

  18 months

• Soft Tissue Complete Response

  In addition to an undetectable PSA, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (Complete Response per RECIST) in order to meet the criteria for PFS. Outcome in subjects who develop radiographically evident metastatic disease while on study will be considered treatment failures independent of their respective PSA values.

  1 year

Secondary Outcomes (5)

• PSA Response Rate

  8 months

• Overall Quality of Life

  1 year

• Non-hematologic Adverse Events

  1 year

• Testosterone and Luteinizing Hormone (LH) Recovery Rates

  8 -10 months

• Correlative Tissue Analysis

  1 year

Study Arms (3)

Abiraterone acetate

EXPERIMENTAL

Group 1 * Abiraterone acetate 1000 mg daily x 8 months * Prednisone 5 mg once daily x 8 months

Drug: Abiraterone acetate

Abiraterone acetate and Degarelix

EXPERIMENTAL

Group 2 Abiraterone acetate 1000 mg daily x 8 months * Prednisone 5 mg once daily x 8 months * Degarelix subcutaneous depot injection q 1 month x 8 months

Drug: Abiraterone acetate plus degarelix

Degarelix

EXPERIMENTAL

Group 3 • Degarelix subcutaneous depot injection q 1 month x 8 months

Drug: Degarelix

Interventions

Abiraterone acetate DRUG

Patients randomized to abiraterone acetate and prednisone (Group 1) will be instructed to take 1000 mg (four 250 mg tablets) of abiraterone acetate orally (PO) at least 1 hour before a meal and 2 hours after a meal every day. These patients will also be treated with prednisone 5 mg once daily with food.

Abiraterone acetate

Abiraterone acetate plus degarelix DRUG

Patients randomized to abiraterone acetate plus degarelix and prednisone (Group 2) will be instructed to take 1000 mg (four 250 mg tablets) of abiraterone acetate orally (PO) at least 1 hour before a meal and 2 hours after a meal every day and prednisone 5 mg once daily with food. Patients will also be given two subcutaneous injections of degarelix 120 mg on Cycle 1, Day 1(starting dose) and 80 mg subcutaneous doses (maintenance doses) every 28 days (±3 days) thereafter.

Abiraterone acetate and Degarelix

Degarelix DRUG

Patients randomized to degarelix alone (Group 3) will be given two subcutaneous injections of degarelix 120 mg on Cycle 1, Day 1 (starting dose) and 80 mg subcutaneous doses (maintenance doses) every 28 days (± 3 days) thereafter.

Degarelix

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent and Authorization for Use and Release of Health and Research Study Information (HIPAA authorization) NOTE: HIPAA authorization may be either included in the informed consent or obtained separately.
• Male aged 18 years and above
• Patients must have undergone local treatment via radical prostatectomy
• Patients who have received primary radiation therapy followed by a salvage radical prostatectomy are eligible.
• Patients who have had post-operative radiation therapy for presumed locally recurrent disease are eligible
• Histologically confirmed prostate cancer (per standards at Institution of participant registration) currently with progressive disease, defined as:
• Rising PSA (50% or more increase to a level of 1 ng/mL or more, based on at least 3 PSA determinations obtained at least 1 week apart). The 50% rise in PSA is across the 3 determinations, and these determinations do not need to be sequential AND
• PSADT ≤ 9 months as calculated according to the Memorial Sloan-Kettering Cancer Center nomogram (http://www.mskcc.org/mskcc/html/10088.cfm) OR
• Rising PSA as defined above AND
• Metastatic disease limited to the presence of pelvic and/or retroperitoneal nodes \< 2 cm in short axis.
• Patients must have a serum testosterone of 150 ng/dL or greater
• ECOG performance status of ≤ 2 (Appendix A)
• Adequate bone marrow, hepatic, and renal function, as evidenced within 14 days prior to treatment initiation by:
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3

You may not qualify if:

• Prior cytotoxic chemotherapy or biologic therapy for prostate cancer
• More than 8 months of prior hormonal therapy (e.g., gonadotropin-releasing hormone analogs, megestrol acetate, or Casodex) Note: Patients who have been on prior hormonal therapy must wait at least 1 year after the drug is fully metabolized to start treatment on protocol.
• Prior ketoconazole, abiraterone acetate, or enzalutamide for the treatment of prostate cancer.
• Known brain metastasis or evidence of metastatic disease by CT scan, physical exam, or bone scan within 4 weeks of registration
• Patients with equivocal uptake on a bone scan that in the clinician's opinion do not definitively constitute metastatic disease are eligible
• Currently active second malignancy
• Significant medical condition other than cancer, that would prevent consistent and compliant participation in the study that would, in the opinion of the investigator, make this protocol unreasonably hazardous including but not limited to:
• Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
• Severe hepatic impairment (Child-Pugh Class C)
• History of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
• Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg); patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
• Active or symptomatic viral hepatitis or chronic liver disease
• History of pituitary or adrenal dysfunction
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or cardiac ejection fraction measurement of \< 50 % at baseline
• Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Janssen Scientific Affairs, LLC: collaborator
• OHSU Knight Cancer Institute: collaborator
• Rutgers Cancer Institute of New Jersey: collaborator
• Endeavor Health: collaborator
• Duke University: collaborator
• Northwestern University Feinberg School of Medicine: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: collaborator
• University of North Carolina: collaborator
• Wayne State University: collaborator
• Perlmutter New York University Cancer Center: collaborator
• Weill Medical College of Cornell University: collaborator
• Ferring Pharmaceuticals: collaborator
• GU Research Network, LLC: collaborator
• University of California, Los Angeles: collaborator

Study Sites (16)

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Karmanos Cancer Institute, Wayne State University

Detroit, Michigan, 48201, United States

Location

Urology Cancer Center and GU Research Network

Omaha, Nebraska, 68130, United States

Location

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering West Harrison

Harrison, New York, 10604, United States

Location

NorthShore University Health System

Long Island City, New York, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medical Center

New York, New York, United States

Location

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Location

Memoral Sloan Kettering Cancer Center at Phelps

Sleepy Hollow, New York, 10591, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Medical Center

Durham, North Carolina, 27701, United States

Location

Oregon Health & Science University Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide

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

Results Point of Contact

• Title: Dr. Howard Scher, MD
• Organization: Memorial Sloan Kettering Cancer Center

scherh@MSKCC.ORG

646-888-4878

Study Officials

• Howard I Scher, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2012
• First Posted: December 18, 2012
• Study Start: December 18, 2012
• Primary Completion: September 28, 2020
• Study Completion: September 28, 2020
• Last Updated: November 19, 2021
• Results First Posted: November 19, 2021

Record last verified: 2020-09

Locations

US (16)