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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 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: October 17, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to determine if newly diagnosed (within previous 3 months) participants with metastatic (spread of cancer cells from one part of the body to another ) 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: Androgen deprivation therapy (ADT)
Drug: Abiraterone acetate Placebo
Drug: Prednisone 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 (OS) [ Time Frame: Time from randomization until death or lost to follow-up or withdrawal of consent or study termination, whichever occurs first, up to Month 60 (5 years) ] [ Designated as safety issue: No ]
    The OS is defined as the time from randomization to date of death from any cause.

  • Radiographic progression-free survival (PFS) [ Time Frame: Time from randomization until death or lost to follow-up or withdrawal of consent or study termination, whichever occurs first, up to Month 60 (5 years) ] [ Designated as safety issue: No ]
    Radiographic PFS is defined as the time from randomization to the occurrence of radiographic progression or death from any cause. Radiographic progression will be assessed for soft tissue lesion using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and bone lesion using modified Prostate Cancer Working Group 2 (PCWG2 ) criteria.


Secondary Outcome Measures:
  • Time to next skeletal-related event [ Time Frame: Up to Month 60 ] [ Designated as safety issue: No ]
    Time to next skeletal related event will be reported.

  • Time to prostate specific antigen (PSA) 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 PSA progression will be calculated by PCWG2 criteria.

  • Time to next subsequent therapy for prostate cancer [ Time Frame: Up to Month 60 ] [ Designated as safety issue: No ]
    Time to next subsequent therapy for prostate cancer will be reported.

  • Time to initiation of chemotherapy [ Time Frame: Up to Month 60 ] [ Designated as safety issue: No ]
    Time to initiation of chemotherapy will be reported.

  • Time to Pain Progression [ Time Frame: Up to Month 60 ] [ Designated as safety issue: No ]
    Time to pain progression is defined as the time from randomization until date of first assessment of increased pain where increased pain event is defined as the first of a participant requiring opiate medication for pain due to prostate cancer metastasis.


Estimated Enrollment: 1200
Study Start Date: February 2013
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abiraterone acetate + Prednisone + ADT
Participants will receive abiraterone acetate tablet at a total dose of 1000 milligram (mg) along with 5 mg capsule of prednisone orally once daily until disease progression, withdrawal of consent or unacceptable toxicity. Stable regimen of androgen deprivation therapy (ADT) will be administered.
Drug: Abiraterone acetate
Abiraterone acetate tablets will be administered orally at a total dose of 1000 mg per day until disease progression, withdrawal of consent or unacceptable toxicity.
Other Name: Zytiga
Drug: Prednisone
Prednisone 5 mg capsule will be administered orally once daily until disease progression, withdrawal of consent or unacceptable toxicity.
Other: Androgen deprivation therapy (ADT)
All participants will receive stable regimen of ADT, that is, lutenizing hormone releasing hormone (LHRH) agonists or surgical castration according to local guidelines until disease progression, withdrawal of consent or unacceptable toxicity.
Drug: Abiraterone acetate Placebo
Placebo matched to abiraterone acetate will be administered orally once daily until disease progression, withdrawal of consent or unacceptable toxicity.
Placebo Comparator: Placebo + Androgen Deprivation Therapy (ADT)
Participants will receive placebo matched to abiraterone acetate and prednisone orally once daily until disease progression, withdrawal of consent or unacceptable toxicity. Stable regimen of ADT will be administered.
Other: Androgen deprivation therapy (ADT)
All participants will receive stable regimen of ADT, that is, lutenizing hormone releasing hormone (LHRH) agonists or surgical castration according to local guidelines until disease progression, withdrawal of consent or unacceptable toxicity.
Drug: Abiraterone acetate Placebo
Placebo matched to abiraterone acetate will be administered orally once daily until disease progression, withdrawal of consent or unacceptable toxicity.
Drug: Prednisone Placebo
Placebo matched to prednisone will be administered orally once daily until disease progression, withdrawal of consent or unacceptable toxicity.

Detailed Description:

This is a randomized (the treatment group is assigned by chance), double-blind (neither physician nor participant knows the treatment that the participant 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 the efficacy of abiraterone acetate and low-dose prednisone in participants with mHNPC . The study consists of 4 parts: Screening Phase (that is, 28 days before study commences on Day 1); Double-blind treatment Phase (consists of 4-week dosing cycles wherein abiraterone acetate will be administered as 1,000 milligram [mg] along with 5 mg prednisone or only placebo orally); Follow-up Phase (every 4 months up to 60 months or until death, lost to follow up, withdrawal of consent or study termination) and Open-label Extension Phase (up to 3 years). Participants will discontinue study treatment at disease progression or unacceptable toxicity unless, in the Investigator's opinion, it is deemed that the participants will continue to derive benefit from study treatment. Participants 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).Efficacy will be evaluated primarily by overall survival and radiographic progression-free survival. Participants' safety will be monitored throughout the study.

  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 greater than or equal to (>=8); presence of 3 or more lesions on bone scan; presence of measurable visceral (excluding lymph node disease) metastasis on CT or MRI Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 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 antagonists or orchiectomy with or without concurrent anti-androgens prior Cycle 1 Day 1; participants 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 311 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: October 17, 2014
Health Authority: United States: Food and Drug Administration
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Japan: Pharmaceuticals and Medical Devices Agency
Ukraine: State Pharmacological Center - Ministry of Health
Ukraine: Ministry of Health
Great Britain: Medicines and Healthcare Products Regulatory Agency
Great Britain: Research Ethics Committee

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

ClinicalTrials.gov processed this record on October 20, 2014