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)

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 3

Conditions: Prostate Neoplasms

Treatments: Drug: Prednisone Placebo; Drug: Abiraterone acetate Placebo; Other: Androgen deprivation therapy (ADT); Drug: Prednisone; Drug: Abiraterone acetate

Study type: Interventional

Funder types: Industry

Identifiers

NCT01715285

212082PCR3011 (Other Identifier)

CR100900

2012-002940-26 (EudraCT Number)

U1111-1135-7146 (Other Identifier)

Details and patient eligibility

About

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 plus low-dose prednisone to androgen deprivation therapy (ADT; lutenizing hormone releasing hormone [LHRH] agonists or surgical castration).

Full 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 plus 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] plus 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.

Enrollment: 1,209 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,209 participants in 2 patient groups, including a placebo group

Abiraterone acetate + Prednisone + ADT

Experimental group

Description:

Participants will receive abiraterone acetate tablet at a total dose of 1000 milligram (mg) plus 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.

Treatment:

Drug: Abiraterone acetate

Other: Androgen deprivation therapy (ADT)

Drug: Prednisone

Placebo + Androgen Deprivation Therapy (ADT)

Placebo Comparator group

Description:

Participants will receive placebo matched to abiraterone acetate plus prednisone orally once daily until disease progression, withdrawal of consent or unacceptable toxicity. Stable regimen of ADT will be administered.

Treatment:

Drug: Abiraterone acetate Placebo

Other: Androgen deprivation therapy (ADT)

Drug: Prednisone Placebo