Study of Abiraterone Acetate Without Exogenous Glucocorticoids in Men With Castration-resistant Prostate Cancer

NCT02025010 | Completed Phase 2 Results DMC

• 1 other identifier: 13-449
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 8

Brief Summary

This study is comparing the safety and effectiveness of abiraterone acetate alone, followed by the addition of prednisone (when the participant's disease worsens or the physician feels it would lessen symptoms of toxicity) versus the current approved treatment regimen which involves the concomitant use of prednisone in conjunction with abiraterone acetate. Additionally, this study is also examining why participants stop responding to treatment with abiraterone acetate by evaluating blood and tissue.

Conditions

Castration-resistant Prostate Cancer

Keywords

Castration-resistant Prostate Cancer; Abiraterone Acetate

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Toxicities That Required the Addition of Prednisone to Manage Symptoms of Persistent or Severe Mineralocorticoid Excess

  Patients requiring prednisone to manage toxicities such as COU-302 any grade or COU-301 grade 3-4 hypertension, hypokalemia and edema per CTCAE v. 4.0 were summarized using frequency and percentage.

  Patients were on abiraterone acetate up to 57 months and toxicities of mineralocorticoid excess were monitored each cycle (1cycle = 28 days).

Secondary Outcomes (14)

• Safety and Tolerability Associated With AA Monotherapy and the Addition of Prednisone to AA.

  Adverse events were assessed continuously on treatment and up to 30 days after going off treatment (up to 55 months).

• Number of Participants Requiring the Addition of Prednisone to Manage Symptoms of Severe Fatigue.

  Patients were on abiraterone acetate up to 57 months.

• Changes in Serum Concentrations of Corticosteroid Intermediates Between the First and Second Assessment Visits.

  1 month

• Changes in Serum Concentrations of ACTH Between Cycle 1 and Cycle 2.

  1 month

• Percent Changes in Serum Concentrations of Androgen (Including Testosterone, DHT and Androgen Precursors) Between Cycle 1 and Cycle 2.

  1 month

Study Arms (1)

abiraterone acetate

EXPERIMENTAL

Participants will be treated with four 250 mg tablets (1,000 mg) of abiraterone acetate (AA) orally on 28-day cycles. For participants who experience persistent or severe mineralocorticoid excess or have PSA progression, prednisone 5 mg by mouth twice daily will be added. Patients will be treated until radiographic disease progression and unacceptable AE or taken off study for other reason.

Drug: abiraterone acetate

Interventions

abiraterone acetate DRUG

Abiraterone acetate is a selective and irreversible inhibitor of CYP17 which has demonstrated clinical efficacy in patients with CRPC. Currently, AA is administered with concomitant prednisone.

Also known as: JNJ21208

abiraterone acetate

Eligibility Criteria

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

You may qualify if:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Be a male ≥ 18 years of age.
• Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate without \>50% neuroendocrine differentiation or small cell histology.
• Participants must have progressive disease as defined by one or more of the following:
• Castrate resistant disease as defined by Prostate cancer working Group (PCWG).\[30\] Participants must have a rise in PSA on two successive determinations at least one week apart and PSA levels ≥ 2 ng/ml (only the screening PSA needs to be ≥ 2 ng/ml) and testosterone levels \< 50 ng/dL.
• Soft tissue progression defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
• Bone disease progression defined by Prostate Cancer Clinical Trials Working Group 2 (PCWG2) with two or more new lesions on bone scan.\[30\]
• Castration-resistant prostate cancer (CRPC) with metastatic disease with at least one site of metastatic disease must be amenable to needle biopsy. Soft tissue biopsy sites include: lymph node or visceral metastases. Bone sites include lumbar vertebrae, pelvic bones and long bones. Excluded sites are thoracic, cervical vertebrae, skull and rib lesions. Biopsy site will be selected with guidance of interventional radiologist determining best site to optimize balance of obtaining useful tissue for analysis and minimizing risk.
• Participants without orchiectomy must be maintained on Luteinizing hormone-releasing hormone (LHRH) agonist/antagonist therapy.
• Participants may have had any number of previous hormonal therapies (antiandrogens including enzalutamide, steroids, estrogens, finasteride, dutasteride, ketoconazole) provided these were discontinued ≥ 4 weeks before starting the trial.
• Participants may have had up to two previous cytotoxic therapeutic regimens provided these were discontinued ≥ 4 weeks before starting the trial.
• At least a 4 week interval from previous prostate cancer treatment other than LHRH agonist/antagonist therapy or bisphosphonates to the start of protocol therapy.
• Participants receiving bisphosphonates therapy can be maintained on this therapy. If participants have not started bisphosphonates, it is recommended that they start treatment after the first biopsy.
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky \>60%, see Appendix A).
• Participants must have normal organ and marrow function as defined below:

You may not qualify if:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Uncontrolled illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or would make prednisone/prednisolone (corticosteroid) use contraindicated.
• 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.
• Thromboembolism within 6 months of Cycle 1, Day 1.
• Severe hepatic impairment (Child-Pugh Class C).
• History of pituitary or adrenal dysfunction.
• Poorly controlled diabetes.
• History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug.
• Have a pre-existing condition that warrants long-term corticosteroid use.
• Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1) individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy, or 2) individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: superficial bladder cancer, basal cell or squamous cell carcinoma of the skin.
• Known brain metastasis.
• Prior therapy with AA.
• Have known allergies, hypersensitivity, or intolerance to AA or prednisone or their excipients.
• Surgery or local prostatic intervention within 30 days of the first dose. In addition, any clinically relevant issues from the surgery must have resolved prior to Cycle 1, Day 1.
• Major surgery or radiation therapy within 4 weeks of Cycle 1, Day 1.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (8)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering Cancer Center Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Cancer Center Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center West Harrison

Harrison, New York, 10604, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center Rockville Centre

Rockville Centre, New York, 11510, United States

Location

Memorial Sloan Kettering Cancer Center Sleepy Hollow

Sleepy Hollow, New York, 10591, United States

Location

Related Publications (1)

• Sperger JM, Emamekhoo H, McKay RR, Stahlfeld CN, Singh A, Chen XE, Kwak L, Gilsdorf CS, Wolfe SK, Wei XX, Silver R, Zhang Z, Morris MJ, Bubley G, Feng FY, Scher HI, Rathkopf D, Dehm SM, Choueiri TK, Halabi S, Armstrong AJ, Wyatt AW, Taplin ME, Zhao SG, Lang JM. Prospective Evaluation of Clinical Outcomes Using a Multiplex Liquid Biopsy Targeting Diverse Resistance Mechanisms in Metastatic Prostate Cancer. J Clin Oncol. 2021 Sep 10;39(26):2926-2937. doi: 10.1200/JCO.21.00169. Epub 2021 Jul 1.

  PMID: 34197212 DERIVED

MeSH Terms

Interventions

Abiraterone Acetate

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Mary-Ellen Taplin, MD
• Organization: Dana-Farber Cancer Institute

mtaplin@partners.org

617-582-7221

Study Officials

• Mary-Ellen Taplin, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigators

Study Record Dates

• First Submitted: December 13, 2013
• First Posted: December 31, 2013
• Study Start: January 27, 2014
• Primary Completion: December 1, 2021
• Study Completion: April 7, 2025
• Last Updated: April 15, 2025
• Results First Posted: November 8, 2022

Record last verified: 2025-04

Locations

US (8)