A Study of Abiraterone Acetate Plus Low-Dose Prednisone Plus Androgen Deprivation Therapy (ADT) Versus ADT Alone in Newly Diagnosed Patients With High-Risk, Metastatic Hormone-Naive Prostate Cancer (mHNPC)

This study is currently recruiting participants.
Verified April 2014 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01715285
First received: October 24, 2012
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to determine if newly diagnosed (within previous 3 months) patients with metastatic hormone-naive prostate cancer (mHNPC) who have high-risk prognostic factors will benefit from the addition of abiraterone acetate and low-dose prednisone to androgen deprivation therapy (ADT; lutenizing hormone releasing hormone [LHRH] agonists or surgical castration).


Condition Intervention Phase
Prostate Neoplasms
Drug: Abiraterone acetate
Drug: Prednisone
Other: ADT (androgen deprivation therapy)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Comparative Study of Abiraterone Acetate Plus Low-Dose Prednisone Plus Androgen Deprivation Therapy (ADT) Versus ADT Alone in Newly Diagnosed Subjects With High-Risk, Metastatic Hormone-naive Prostate Cancer (mHNPC)

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Overall survival [ Time Frame: Up to the time of death from any cause (up to Month 60) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiographic progression-free survival [ Time Frame: Up to disease progression or death from any cause (up to Month 60) ] [ Designated as safety issue: No ]
  • Time to next skeletal-related event [ Time Frame: Up to Month 60 ] [ Designated as safety issue: No ]
  • Time to prostate specific antigen progression [ Time Frame: Cycles 1-13 Day 1, Day 1 every other cycle starting Cycle 14 to end-of-treatment up to disease progression ] [ Designated as safety issue: No ]
  • Time to next subsequent therapy for prostate cancer [ Time Frame: Up to Month 60 ] [ Designated as safety issue: No ]
  • Time to initiation of chemotherapy [ Time Frame: Up to Month 60 ] [ Designated as safety issue: No ]
  • Change in miRNA expression level [ Time Frame: Cycle 1 Day 1, Cycle 3 Day 1, and end-of-treatment visit (up to 30 days after last dose of study drug) ] [ Designated as safety issue: No ]
  • Change in mRNA expression level [ Time Frame: Cycle 1 Day 1, Cycle 3 Day 1, and end-of-treatment visit (up to 30 days after last dose of study drug) ] [ Designated as safety issue: No ]
  • Number of participants affected by an adverse event [ Time Frame: Up to 30 days after the last dose of study drug ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1270
Study Start Date: February 2013
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abiraterone acetate + prednisone + ADT Drug: Abiraterone acetate
Abiraterone 1000 mg (4 x 250 mg tablets) taken orally once daily
Drug: Prednisone
Prednisone 5 mg capsule taken orally once daily
Other: ADT (androgen deprivation therapy)
Stable regimen of ADT or surgical castration according to local guidelines
Placebo Comparator: Placebo + ADT Other: ADT (androgen deprivation therapy)
Stable regimen of ADT or surgical castration according to local guidelines
Drug: Placebo
Placebo matched for abiraterone acetate 4 tablets taken orally once daily
Drug: Placebo
Placebo matched for prednisone 1 capsule taken orally once daily

Detailed Description:

This is a randomized (the treatment group is assigned by chance), double-blind (neither physician nor patient knows the treatment that the patient receives), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study designed to determine if newly diagnosed (within previous 3 months) patients with mHNPC who have high-risk prognostic factors will benefit from the addition of abiraterone acetate and low-dose prednisone to ADT (LHRH agonists or surgical castration). Approximately 1270 patients will be enrolled in this study. Patients will be stratified by presence of visceral disease and Eastern Cooperative Oncology Group performance grade prior to randomization. The study protocol consists of the following phases: screening, double-blind treatment, and follow-up phase of up to 60 months to monitor survival status and subsequent prostate cancer therapy. Patients will be randomized in a 1:1 ratio to the active treatment group (abiraterone acetate 1000 mg daily plus prednisone 5 mg daily plus ADT) or the control group (ADT plus placebos). Treatment in 28-day cycles will continue until disease progression or the occurrence of unacceptable toxicity. Patients will be monitored for efficacy and safety throughout the study. Two interim analyses and a final analysis are planned for this study. In the event of a positive study result at either of the interim analyses or at the time of the final analysis, all participants will have the opportunity to enroll in an open-label extension phase that will allow participants to receive active drug (abiraterone acetate plus prednisone) for up to 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed metastatic prostate cancer within 3 months prior to randomization with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology
  • Distant metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan
  • At least 2 of the following high-risk prognostic factors: Gleason score of >=8; presence of 3 or more lesions on bone scan; presence of measurable visceral (excluding lymph node disease) metastasis on CT or MRI scan
  • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2
  • Adequate hematologic, hepatic, and renal function
  • Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

  • Active infection or other medical condition that would make prednisone use contraindicated
  • Any chronic medical condition requiring a higher systemic dose of corticosteroid than 5 mg prednisone per day
  • Pathological finding consistent with small cell carcinoma of the prostate
  • Known brain metastasis
  • Any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer (the following exception are permitted): up to 3 months of androgen deprivation therapy (ADT) with lutenizing hormone releasing hormone agonists or orchiectomy with or without concurrent anti-androgens prior Cycle 1 Day 1; patients may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 28 days prior to Cycle 1 Day 1); all adverse events associated with these procedures must be resolved at least to Grade 1 by Cycle 1 Day 1
  • Uncontrolled hypertension (systolic blood pressure >=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; ascites or bleeding disorders secondary to hepatic dysfunction
  • History of adrenal dysfunction
  • Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events or history of cardiac failure in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease
  • Atrial fibrillation or other cardiac arrhythmia requiring pharmacotherapy
  • Other malignancy (within 5 years), except non-melanoma skin cancer
  • Administration of an investigational therapeutic or invasive surgical procedure (not including surgical castration) within 28 days of Cycle 1 Day 1 or currently enrolled in an investigational study
  • Any condition or situation which, in the opinion of the investigator, would put the patient at risk, may confound study results, or interfere with the patient's participation in this study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01715285

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Show 301 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01715285     History of Changes
Other Study ID Numbers: CR100900, 212082PCR3011, 2012-002940-26, U1111-1135-7146
Study First Received: October 24, 2012
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Great Britain: Medicines and Healthcare Products Regulatory Agency
Ukraine: Ministry of Health
Japan: Pharmaceuticals and Medical Devices Agency
Ukraine: State Pharmacological Center - Ministry of Health

Keywords provided by Janssen Research & Development, LLC:
Prostate neoplasms
Prostate cancer
Metastatic prostate cancer
Abiraterone acetate
ZYTIGA
Prednisone
Androgen deprivation therapy

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Androgens
Prednisone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Glucocorticoids
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 17, 2014