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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)

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ClinicalTrials.gov Identifier: NCT01715285
Recruitment Status : Active, not recruiting
First Posted : October 26, 2012
Results First Posted : October 15, 2018
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
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 or disease Intervention/treatment Phase
Prostate Neoplasms Drug: Abiraterone acetate Drug: Prednisone Other: Androgen deprivation therapy (ADT) Drug: Abiraterone acetate Placebo Drug: Prednisone Placebo Phase 3

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) Open-label Extension (OLE) Phase. Participants in the Double-blind Treatment Phase will have the opportunity to enroll into the OLE Phase. The OLE Phase will allow participants to receive active drug (abiraterone acetate plus prednisone) until Long-term Extension (LTE) Phase for an additional period of 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1209 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, 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)
Actual Study Start Date : February 12, 2013
Actual Primary Completion Date : October 31, 2016
Estimated Study Completion Date : August 3, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. Radiographic Progression-Free Survival (PFS) [ Time Frame: Upto 44 months ]
    Radiographic PFS was defined as the time interval from randomization to the first date of radiographic progression or death. Radiographic progression included progression by bone scan (according to modified Prostate Cancer Working Group 2 [PCWG2] criteria) and progression of soft tissue lesions by computed tomography (CT) or magnetic resonance imaging (MRI) (according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria).

  2. Overall Survival (OS) [ Time Frame: Up to 44 months ]
    Overall survival was defined as the time from randomization to date of death from any cause.


Secondary Outcome Measures :
  1. Time to Initiation of Chemotherapy [ Time Frame: Up to 44 months ]
    Time to initiation of chemotherapy was defined as the time interval from the date of randomization to the date of initiation of chemotherapy for prostate cancer.

  2. Time to Subsequent Therapy for Prostate Cancer [ Time Frame: Up to 44 months ]
    Time to subsequent therapy was defined as the time interval from the date of randomization to the date of initiation of subsequent therapy for prostate cancer.

  3. Time to Pain Progression [ Time Frame: upto 44 months ]
    Time to pain progression was defined as the time interval from randomization to the first date a participant experienced a greater than or equal to (>=) 30 percent (%) increase in Brief Pain Inventory-Short Form (BPI-SF) from baseline in the BPI-SF worst pain intensity (Item 3) observed at 2 consecutive evaluations (>=4) weeks apart. BPI-SF was an 11-item questionnaire, designed to assess severity and impact of pain on daily functions. Total score ranged from 0 to 10 with 0 representing "no pain" and 10 representing" pain as bad as you can imagine.

  4. Time to Skeletal-Related Event [ Time Frame: Upto 44 months ]
    Time to skeletal-related event was defined as the earliest of the following: clinical or pathological fracture, spinal cord compression, palliative radiation to bone, or surgery to bone.

  5. Time to Prostate-Specific Antigen (PSA) Progression [ Time Frame: Upto 44 months ]
    Time to PSA progression was defined as the time interval from the date of randomization to the date of PSA progression, according to PCWG2 criteria.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01715285


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Argentina
Buenos Aires, Argentina
Cordoba, Argentina
La Rioja, Argentina
Rosario, Argentina
Australia
Adelaide, Australia
Footscray, Australia
Liverpool, Australia
Malvern, Australia
Randwick, Australia
Wahroonga, Australia
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Antwerpen, Belgium
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Novo Hamburgo, Brazil
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Sofia, Bulgaria
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Canada
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Chile
Santiago, Chile
China
Beijing, China
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Chongqing, China
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Nanjing, China
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Su Zhou, China
Tianjin, China
Wuhan, China
Colombia
Bogota, Colombia
Floridablanca, Colombia
Medellin, Colombia
Czechia
Hradec Kralove, Czechia
Olomouc, Czechia
Plzen, Czechia
Praha 10, Czechia
Praha 2, Czechia
Praha 4, Czechia
Denmark
Aarhus N, Denmark
Holsterbro, Denmark
Odense N/A, Denmark
Roskilde, Denmark
Vejle, Denmark
Finland
Oulu, Finland
Tampere, Finland
France
La Chaussee St Victor, France
Lille, France
Montpellier, France
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Villejuif Cedex, France
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Düsseldorf, Germany
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Kuala Lumpur N/A, Malaysia
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Kuching, Malaysia
Mexico
Chihuahua, Mexico
Cuernavaca, Mexico
Durango, Mexico
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Pachuca De Soto, Mexico
Zapopan, Mexico
Netherlands
Alkmaar, Netherlands
Amsterdam Zuidoost, Netherlands
Amsterdam, Netherlands
Hilversum, Netherlands
Hoofddorp, Netherlands
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Rotterdam, Netherlands
New Zealand
Auckland, New Zealand
Christchurch, New Zealand
Hamilton, New Zealand
Tauranga, New Zealand
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Lodz, Poland
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Romania
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Cluj Napoca, Romania
Iasi, Romania
Timisoara, Romania
Russian Federation
Chelyabinsk, Russian Federation
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Ivanovo, Russian Federation
Izhevsk, Russian Federation
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Nizhny Novgorod, Russian Federation
Obninsk, Kaluga Region, Russian Federation
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Ryazan, Russian Federation
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Sochi, Russian Federation
St.-Petersburg, Russian Federation
Stavropol, Russian Federation
Tumen, Russian Federation
Ufa, Russian Federation
Volgograd, Russian Federation
Yoshkar-Ola, Russian Federation
Slovakia
Košice-Šaca, Slovakia
Martin, Slovakia
Piestany, Slovakia
Prešov, Slovakia
Rimavska Sobota, Slovakia
Trnava, Slovakia
South Africa
George, South Africa
Port Elizabeth, South Africa
Pretoria, South Africa
Vosloorus, South Africa
Spain
Barcelona, Spain
Cordoba, Spain
Coruña, Spain
Madrid N/A, Spain
Madrid, Spain
Murcia N/A, Spain
Sweden
Göteborg, Sweden
Malmö, Sweden
Stockholm, Sweden
Umeå, Sweden
Uppsala, Sweden
Turkey
Adana, Turkey
Ankara, Turkey
Istanbul, Turkey
Izmir, Turkey
Zonguldak, Turkey
Ukraine
Cherkassy, Ukraine
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United Kingdom
Cambridge, United Kingdom
Glasgow, United Kingdom
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Nottingham, United Kingdom
Oxford, United Kingdom
Plymouth, United Kingdom
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01715285     History of Changes
Other Study ID Numbers: CR100900
212082PCR3011 ( Other Identifier: Janssen Research & Development, LLC )
2012-002940-26 ( EudraCT Number )
U1111-1135-7146 ( Other Identifier: Universal Trial Number )
First Posted: October 26, 2012    Key Record Dates
Results First Posted: October 15, 2018
Last Update Posted: October 15, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Device Product: No

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:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Hormones
Prednisone
Abiraterone Acetate
Androgens
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Inflammatory Agents
Glucocorticoids
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors