Abiraterone Acetate in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00887198
First received: April 18, 2009
Last updated: May 28, 2015
Last verified: May 2015
  Purpose

This is a phase 3 study to compare the clinical benefit of abiraterone acetate plus prednisone with placebo plus prednisone in asymptomatic or mildly symptomatic patients with metastatic castration-resistant prostate cancer (CRPC).


Condition Intervention Phase
Prostate Cancer
Drug: Abiraterone acetate
Drug: Placebo
Drug: Prednisone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Placebo-Controlled Study of Abiraterone Acetate (CB7630) Plus Prednisone in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization (Day 1) up to end of study (Month 60) ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization to date of death from any cause.

  • Radiographic Progression-free Survival (rPFS) [ Time Frame: From randomization (Day 1) up to first radiographic progression or cutoff date (Month 18) ] [ Designated as safety issue: No ]
    The rPFS was defined as the time from randomization to the occurrence of one of the following: 1) a participant was considered to have progressed by bone scan if - a) the first bone scan with greater than or equal to (>=) 2 new lesions compared to baseline was observed in less than (<) 12 weeks from randomization and was confirmed by a second bone scan taken >=6 weeks later showing >=2 additional new lesions (a total of >=4 new lesions compared to baseline), b) the first bone scan with >=2 new lesions compared to baseline was observed in >=12 weeks from randomization and the new lesions were verified on the next bone scan >=6 weeks later (a total of >=2 new lesions compared to baseline); 2) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI); 3) death from any cause.


Secondary Outcome Measures:
  • Time to Opiate Use for Prostate Cancer Pain [ Time Frame: From randomization (Day 1) up to first opiate use or end of study (Month 60) ] [ Designated as safety issue: No ]
    The time interval from the date of randomization to the date of opiate use for cancer pain. Participants who have no opiate use at the time of analysis were censored at the last known date of no opiate use for cancer pain. Participants with no assessment were censored at the date of randomization.

  • Time to Initiation of Cytotoxic Chemotherapy [ Time Frame: From randomization (Day 1) up to initiation of cytotoxic chemotherapy or cutoff date (Month 18) ] [ Designated as safety issue: No ]
    The time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy for prostate cancer. Participants who had no cytotoxic chemotherapy administration at the time of analysis were censored at the last known date when no cytotoxic chemotherapy was administered. Participants with no assessment were censored at the date of randomization.

  • Time to Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Score by >=1 Point [ Time Frame: From randomization (Day 1) up to first radiographic progression or cutoff date (Month 18) ] [ Designated as safety issue: No ]
    The time interval from the date of randomization to the first date at which there was at least a 1 grade change (worsening) in the ECOG performance status grade. Participants who had no deterioration in ECOG performance status grade at the time of the analysis were censored at the last known date of no deterioration. ECOG is a 5-point scale, where 0=Fully active, 1=Ambulatory, carry out work of sedentary nature, 2=Ambulatory, capable of all self-care, 3=Capable of limited self-care, confined to bed or chair more than 50% of waking hours, 4=Completely disabled, no self-care, totally confined to bed or chair, 5=Dead. Participants with no assessment were censored at the date of randomization.

  • Time to Prostate-specific Antigen (PSA) Progression [ Time Frame: From randomization (Day 1) up to date of PSA progerssion or cutoff date (Month 18) ] [ Designated as safety issue: No ]
    The time interval from the date of randomization to the date of PSA progression as defined in the protocol-specific prostate cancer Working Group 2 (PCWG2) criteria. A participant was considered to have a PSA progression if the PSA level had a 25 percent (%) or greater increase from nadir and an absolute increase of 2 nanogram/milliliter ((ng/mL) or more, which is confirmed by a second value obtained in 3 or more weeks. Participants who had no PSA progression at the time of the analysis were censored at the last known date of no PSA progression. Participants with no on-study PSA assessment or no baseline PSA assessment were censored at the date of randomization.

  • Number of Participants With Treatment Emergent Adverse Events [ Time Frame: From first dose of study drug up to 30 days after the last dose of study drug ] [ Designated as safety issue: No ]
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to 30 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state.

  • Mean Plasma Concentrations of Abiraterone [ Time Frame: Up to Cycle 5, Day 1 ] [ Designated as safety issue: No ]
  • Maximum Plasma Concentrations of Abiraterone [ Time Frame: Up to Cycle 5, Day 1 ] [ Designated as safety issue: No ]
  • Area Under the Plasma Concentration-time Curve From Time 0 to Time the Last Quantifiable Concentration of Abiraterone (AUC[0-infinity]) [ Time Frame: Up to Cycle 5, Day 1 ] [ Designated as safety issue: No ]
    The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.

  • Elimination Half-Life (t1/2) [ Time Frame: Up to Cycle 5, Day 1 ] [ Designated as safety issue: No ]
    The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).


Enrollment: 1088
Study Start Date: April 2009
Estimated Study Completion Date: May 2017
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo + prednisone
Placebo plus prednisone
Drug: Placebo
4 placebo tablets per day taken orally.
Drug: Prednisone
5 mg tablet orally twice daily.
Experimental: Abiraterone + prednisone
Abiraterone acetate plus prednisone
Drug: Abiraterone acetate
1000 mg per day (4 x 250-mg tablets) taken orally.
Drug: Prednisone
5 mg tablet orally twice daily.

Detailed Description:

This is a randomized (individuals will be assigned by chance to study treatments), double-blind (individuals and study personnel will not know the identity of study treatments), 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 in approximately 1,000 medically or surgically castrated male patients with metastatic CRPC who have shown tumor progression and are asymptomatic or mildly symptomatic. The study period will consist of screening, treatment, and follow-up phases. Patients will receive study treatment (abiraterone acetate or placebo) plus prednisone until radiographic progression of disease and/or unequivocal clinical progression. Efficacy evaluations will be performed throughout the treatment period and safety will be assessed until 30 days after the last dose of abiraterone acetate. throughout the study. Follow-up will continue for up to 60 months (5 years) or until the patient dies, is lost to follow-up, or withdraws informed consent. At the interim analysis of overall survival (OS; 43% of death events), the independent data monitoring committee (IDMC) reviewed the efficacy and safety data and concluded that all of the data pointed to a significant advantage for patients in one arm of the study compared with the other arm thereby unanimously recommending unblinding the study and allowing crossover from the placebo arm to active therapy. Patients currently receiving placebo will be offered crossover therapy to abiraterone acetate. Treatment for patients who were originally randomized to the abiraterone acetate treatment group will not change. Patients will be discontinued from long term follow-up at the time of the Clinical Cut-Off Date for Final Analysis (CCO-FA); however, patients still receiving treatment with abiraterone acetate at the CCO-FA will be offered to receive continued treatment for an additional period of up to 3 years or until disease progression or unacceptable toxicity. For these patients, safety assessment will be performed while continuing treatment, and for 30 days after the last dose of abiraterone acetate.

  Eligibility

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

Inclusion Criteria:

  • Metastatic castration-resistant prostate cancer (CRPC)
  • Previous anti-androgen therapy and progression after withdrawal
  • ECOG performance status of either 0 or 1
  • Medical or surgical castration with testosterone less than 50 ng/dL
  • Life expectancy of at least 6 months

Exclusion Criteria:

  • Prior cytotoxic chemotherapy or biologic therapy for CRPC
  • Prior ketoconazole for prostate cancer
  • Known brain metastasis or visceral organ metastasis
  • Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime within 4 weeks of 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: NCT00887198

  Show 135 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided by Janssen Research & Development, LLC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT00887198     History of Changes
Other Study ID Numbers: CR016927, COU-AA-302, 2008-008004-41
Study First Received: April 18, 2009
Results First Received: March 30, 2015
Last Updated: May 28, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Prostate cancer
Abiraterone acetate
CB7630
CRPC
Metastatic castration-resistant prostate cancer
hormone refractory prostate cancer

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

ClinicalTrials.gov processed this record on August 03, 2015