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

October 25, 2021 updated by: Memorial Sloan Kettering Cancer Center

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
124

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: 18 months
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
Time Frame: 1 year
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
PSA Response Rate
Time Frame: 8 months
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
Time Frame: 1 year
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
Time Frame: 1 year
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
Time Frame: 8 -10 months
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
Time Frame: 1 year
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Memorial Sloan Kettering Cancer Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Howard I Scher, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 18, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 28, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 28, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 14, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 14, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 18, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 19, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 12-187

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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