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

A Phase 2, Randomized, 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

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Abiraterone acetate; Drug: Abiraterone acetate plus degarelix; Drug: Degarelix

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University, Feinberg School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute, Wayne State University
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Urology Cancer Center and GU Research Network
  • New Jersey
    • Basking Ridge, New Jersey, United States
      • Memoral Sloan Kettering Cancer Center
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute Of New Jersey
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center @ Suffolk
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering West Harrison
    • Long Island City, New York, United States
      • Northshore University Health System
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States
      • Weill Cornell Medical Center
    • Rockville Centre, New York, United States
      • Memorial Sloan Kettering at Mercy Medical Center
    • Sleepy Hollow, New York, United States, 10591
      • Memoral Sloan Kettering Cancer Center at Phelps
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
    • Durham, North Carolina, United States, 27701
      • Duke University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• 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
• Hemoglobin ≥ 9 g/dL without need for hematopoietic growth factor or transfusion support within 30 days prior to treatment initiation
• Aspartate aminotransferase (AST) ≤ 1.5 times the upper limit of the normal range (x ULN)
• Alanine aminotransferase (ALT) ≤ 1.5 x ULN
• Total bilirubin ≤ 1.5 x ULN
• Serum creatinine of ≤ 1.5 mg/dl or Calculated creatinine clearance of ≥ 60 mL/min
• Serum albumin ≥ 3.0 g/dL
• Serum potassium ≥ 3.5 mEq/L
• Prothrombin time (PT) ≤ 1.5 x ULN (or international normalized ratio [INR] ≤ 1.3) unless the patient is receiving anticoagulant therapy
• Partial thromboplastin time (PTT) ≤ 1.5 x ULN unless the patient is receiving anticoagulant therapy At least 4 weeks and recovery to Grade 0-1 from reversible effects of prior surgery (i.e., incisional pain, wound drainage)
• Able to swallow the study drug whole as a tablet
• Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken
• Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator during the study and for 1 week after last dose of abiraterone acetate.

Exclusion Criteria:

• 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
• Uncontrolled diabetes mellitus
• Active psychiatric condition Use of any prohibited concomitant medications (Section 5.5) within 30 days prior to Cycle 1, Day 1
• Pre-existing condition that warrants long-term corticosteroid use in excess of study dose
• Grade > 2 treatment-related toxicity from prior therapy
• Known allergies, hypersensitivity or intolerance to abiraterone acetate, prednisone or degarelix
• Administration of an investigational therapeutic within 30 days of Cycle 1, Day1
• Any condition which, in the opinion of the investigator, would preclude participation in this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abiraterone acetate; Group 1; Abiraterone acetate 1000 mg daily x 8 months; Prednisone 5 mg once daily x 8 months	Drug: Abiraterone acetate; 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.
Experimental: Abiraterone acetate and Degarelix; 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; 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.
Experimental: Degarelix; Group 3 • Degarelix subcutaneous depot injection q 1 month x 8 months	Drug: Degarelix; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA Response Rate	The percentage of patients with a non-castrate level of testosterone (>150 ng/dL) and an undetectable PSA at 8 months from PSA0 will be measured.	8 months
Overall Quality of Life	with particular attention to libido, potency, anxiety, depression, hot flashes, and fatigue. Effects of each arm on health-related quality of life will be assessed via PRO Survey (Appendix C) completed on paper by the patient at the following study visits: Up to 30 Days Prior to Randomization, each Day 1 of Treatment Cycle, End of Treatment, and each Post-Treatment Follow-up.Effects of each arm on quality of life,	1 year
Non-hematologic Adverse Events	Safety will be evaluated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations and clinical laboratory tests throughout the conduct of the study.	1 year
Testosterone and Luteinizing Hormone (LH) Recovery Rates	Testosterone and LH recovery rates will be measured at 8 months from the start of randomization and at each month of the 10 month follow up period.	8 -10 months
Correlative Tissue Analysis	Tissue samples will be utilized for morphologic assessment, percent tumor involvement (if applicable), and immunohistochemistry. The immunohistochemical markers assessed may be AR, PTEN, PSMA, fatty acid synthase (FASN), phospho-AMPK, phospho-ACC, phospho-S6 kinase, phospho-Akt for the assessment of the AMPK, lipid synthesis, mTOR pathways, and immunological markers.	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: University of California, Los Angeles; Ferring Pharmaceuticals; Wayne State University; Janssen Scientific Affairs, LLC; Duke University; Weill Medical College of Cornell University; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; NorthShore University HealthSystem; Northwestern University Feinberg School of Medicine; OHSU Knight Cancer Institute; Rutgers Cancer Institute of New Jersey; University of North Carolina; Perlmutter New York University Cancer Center; GU Research Network, LLC
• Investigators: Principal Investigator: Howard I Scher, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2012
• Primary Completion (Actual): September 28, 2020
• Study Completion (Actual): September 28, 2020

Study Registration Dates

• First Submitted: December 14, 2012
• First Submitted That Met QC Criteria: December 14, 2012
• First Posted (Estimate): December 18, 2012

Study Record Updates

• Last Update Posted (Actual): November 19, 2021
• Last Update Submitted That Met QC Criteria: October 25, 2021
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: PREDNISONE; ABIRATERONE ACETATE (CB 7630); DEGARELIX; 12-187
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Abiraterone Acetate
• Other Study ID Numbers: 12-187