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Trial record 1 of 1 for:    NCT01867710
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Abiraterone With Different Steroid Regimens for Side Effect Related to Mineralcorticoid Excess Prevention in Prostate Cancer Prior to Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01867710
Recruitment Status : Completed
First Posted : June 4, 2013
Results First Posted : May 11, 2016
Last Update Posted : July 5, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutica N.V., Belgium

Brief Summary:
The purpose of the study is to determine the safety and clinical benefit of the combinations of abiraterone acetate and prednisone or abiraterone and dexamethasone in prostate cancer patients. Prednisone will be given at one of three different dose schedules. Dexamethasone will be given at one dose schedule. This will include looking at what side effects occur and how often they occur. In addition the impact of the study drug on quality of life and pain will be evaluated. The study will also collect data on subsequent treatment of patients after they come off the study drug (approximately 4.5 years after the start of study treatment of the first subject participating in the study). By analyzing blood samples, the study aims to identify if some markers could help to understand if the treatment with abiraterone is effective and also help to understand if patients can become resistant.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Abiraterone Acetate Drug: Prednisone 5 mg twice daily Drug: Prednisone 5 mg once daily Drug: Prednisone 2.5 mg twice daily Drug: Dexamethasone 0.5 mg once daily Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 164 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Study Evaluating Abiraterone Acetate With Different Steroid Regimens for Preventing Symptoms Associated With Mineralocorticoid Excess in Asymptomatic, Chemotherapy-naïve and Metastatic Castration-resistant Prostate Cancer (mCRPC) Patients
Actual Study Start Date : July 16, 2013
Actual Primary Completion Date : April 20, 2015
Actual Study Completion Date : June 5, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AA + prednisone 5 mg twice daily
Abiraterone acetate in combination with prednisone 5 mg twice daily
Drug: Abiraterone Acetate
Type = exact number; unit = mg; number = 1000; form = tablet; route = oral; taken as four 250 mg tablets once daily at least 2 hours after eating and no food should be eaten for at least 1 hour after taking the tablets.

Drug: Prednisone 5 mg twice daily
type = exact number; unit = mg; number = 5; form = tablet; route = oral; taken twice daily, the first dose in the morning after a meal and the second dose after a minimum interval of 8 hours in the late afternoon or early evening, after a meal

Experimental: AA + prednisone 5 mg once daily
Abiraterone acetate in combination with prednisone 5 mg once daily dose
Drug: Abiraterone Acetate
Type = exact number; unit = mg; number = 1000; form = tablet; route = oral; taken as four 250 mg tablets once daily at least 2 hours after eating and no food should be eaten for at least 1 hour after taking the tablets.

Drug: Prednisone 5 mg once daily
type = exact number; unit = mg; number = 5; form = tablet; route = oral; taken once daily, in the morning after a meal

Experimental: AA + prednisone 2.5 mg twice daily
Abiraterone acetate in combination with prednisone 2.5 mg twice daily
Drug: Abiraterone Acetate
Type = exact number; unit = mg; number = 1000; form = tablet; route = oral; taken as four 250 mg tablets once daily at least 2 hours after eating and no food should be eaten for at least 1 hour after taking the tablets.

Drug: Prednisone 2.5 mg twice daily
type = exact number; unit = mg; number = 2.5; form = tablet; route = oral; taken twice daily, the first dose in the morning after a meal and the second dose after a minimum interval of 8 hours in the late afternoon or early evening, after a meal

Experimental: AA + dexamethasone 0.5 mg once daily
Abiraterone acetate in combination with dexamethasone 0.5 mg once daily
Drug: Abiraterone Acetate
Type = exact number; unit = mg; number = 1000; form = tablet; route = oral; taken as four 250 mg tablets once daily at least 2 hours after eating and no food should be eaten for at least 1 hour after taking the tablets.

Drug: Dexamethasone 0.5 mg once daily
type = exact number; unit = mg; number = 0.5; form = tablet; route = oral; taken once daily, in the morning after breakfast




Primary Outcome Measures :
  1. Percentage of Participants Experiencing Neither of the 2 Mineralocorticoid Excess Toxicity During the First 24 Weeks of Treatment [ Time Frame: Week 24 ]
    No mineralocorticoid excess is defined as experiencing neither of the 2 mineralocorticoid excess toxicities, that is, neither hypokalemia nor hypertension.


Secondary Outcome Measures :
  1. Percentage of Participants With Confirmed Prostate Specific Antigen (PSA) Response Rate [Greater Than or Equal to (>=) 50 Percent (%) Decline From Baseline] at Week 12 [ Time Frame: Week 12 ]
    The PSA response is defined as a >= 50% decline from baseline according to the adapted Prostate Cancer Working Group 2 (PCWG2) criteria. For a PSA response to be confirmed, an additional PSA measurement obtained 4 or more weeks later has to show >=50% decline from baseline.

  2. Change From Baseline to Endpoint in Brief Pain Inventory- Short Form (BPI-SF) Score: Worst Pain [ Time Frame: Baseline up to the Endpoint (last post-baseline assessment value during 156 weeks of main study treatment period [MSTP]) ]
    BPI-SF is 11-item self-reported questionnaire designed to assess severity and impact of pain on daily functions (pain interference). It includes 4 questions that assess pain intensity/severity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). BPI-SF scores range from 0=No pain to 10=Pain as bad as you can imagine; Higher scores indicate greater pain. Worst pain item has a scale of 0 to 10 with 0 indicating "No pain" and 10 indicating "Pain as bad as you can imagine". Last observation carried forward (LOCF) approach used for endpoint analysis. Last observation defined as last visit with non-missing data for parameter analyzed.

  3. Change From Baseline to Endpoint in Brief Pain Inventory- Short Form (BPI-SF) Score: Pain Intensity Subscale [ Time Frame: Baseline up to the Endpoint (last post-baseline assessment value during 156 weeks of MSTP) ]
    BPI-SF is 11-item self-reported questionnaire designed to assess severity and impact of pain on daily functions (pain interference). It includes 4 questions that assess pain intensity/severity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). BPI-SF scores range from 0=No pain to 10=Pain as bad as you can imagine; Higher scores indicate greater pain. Pain Severity Index is the mean of the 4 pain scores (worst, least, average, and right now) on the BPI-SF; range is 0=No pain to 10=Pain as bad as you can imagine; A higher score indicates greater pain severity. LOCF approach used for endpoint analysis. Last observation is defined as last visit with non-missing data for parameter analyzed.

  4. Change From Baseline to Endpoint in Brief Pain Inventory- Short Form (BPI-SF) Score: Pain Interference Subscale [ Time Frame: Baseline up to the Endpoint (last post-baseline assessment value during 156 weeks of MSTP) ]
    BPI-SF is 11-item self-reported questionnaire designed to assess severity and impact of pain on daily functions (pain interference). It includes 4 questions that assess pain intensity/severity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). BPI-SF scores range from 0=No pain to 10=Pain as bad as you can imagine; Higher scores indicate greater pain. Pain Interference Index is the mean of the scores for the 7 items of the BPI-SF; range is 0=Does not interfere to 10=Completely interferes. LOCF approach used for endpoint analysis. Last observation is defined as last visit with non-missing data for parameter analyzed.

  5. Change From Baseline to Endpoint in EuroQol-5 Dimension-5 Level (EQ-5D-5L): Index Score [ Time Frame: Baseline up to the Endpoint (last post-baseline assessment value during 156 weeks of MSTP) ]
    EQ-5D-5L measures health outcome self-completed by respondents. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). The descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each has 5 levels (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a Health Status Index (HSI). HSI ranges from -0.148 to 0.949 and is anchored at 0 (health state value equal to dead) and 1 (full health). LOCF approach used for endpoint analysis. Last observation is defined as last visit with non-missing data for parameter analyzed.

  6. Change From Baseline to Endpoint in EuroQol-5 Dimension-5 Level (EQ-5D-5L): EQ-VAS [ Time Frame: Baseline up to the Endpoint (last post-baseline assessment value during 156 weeks of MSTP) ]
    EQ-5D-5L measures health outcome self-completed by respondents. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). EQ-VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine). LOCF approach used for endpoint analysis. Last observation is defined as last visit with non-missing data for parameter analyzed.

  7. Change From Baseline to Endpoint in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire Score [ Time Frame: Baseline up to the Endpoint (last post-baseline assessment value during 156 weeks of MSTP) ]
    FACT-P is a 39-item participant rated questionnaire which consists of 5 subscales assessing physical well-being (7 items; score range 0-28), social/family well-being (7 items; score range 0-28), emotional well-being (6 items; score range 0-24), functional well-being (7 items; score range 0-28), prostate-specific concerns (12 items; score range 0-48). Each item rated on 0 to 4 Likert type scale, then combined to produce subscale scores for each domain, as well as global quality of life (QoL) score that ranges from 0 to 156. Higher scores represent better QoL. Additional Concerns subscale has 12 items, each with a score 0-6 making a total subscale range 0-72 (higher scores are better). Missing data imputed as per FACT-P Ver4 scoring system (sum of item scores*number of items in subscale/number of items answered).

  8. Progression-Free Survival (PFS) [ Time Frame: Up to 4.9 years ]
    PFS: Time from randomization to one of following: radiographic progression (RP), clinical progression (CP) or death. RP- per PCWG2 criteria and modified RECIST as time from randomization to one of following: 1) considered to have progressed by bone scan if: a) first scan with >=2 new lesions compared to baseline at <12 weeks from randomization and confirmed by second scan >=6 weeks later with >=2 additional new lesions, b) first scan with >=2 new lesions compared to baseline at >=12 weeks from randomization and new lesions on next bone scan >=6 weeks later; 2) Progression of soft tissue lesions per modified RECIST; CP: cancer pain requiring initiation of chronic use of opiate analgesia (oral use for >=3 weeks; parenteral use for >=7 days), Or immediate need to initiate cytotoxic chemotherapy or either radiation therapy or surgical intervention for complications due to tumor progression, even in absence of RP, Or deterioration in ECOG performance status to grade 3 or above.

  9. Time to Prostate-Specific Antigen (PSA) Progression [ Time Frame: Up to 156 weeks ]
    Time to PSA progression was defined as time interval from the date of randomization to the date of the first prostate-specific antigen (PSA) progression as defined in the protocol-specific Prostate Specific Antigen Working Group 2 (PSAWG2) criteria during the main study treatment period. PCWG2 defines PSA progression as the date that a 25 percent (%) or greater increase and an absolute increase of 2 nanogram per milliliter (ng/mL) or more from the nadir is documented, which is confirmed by a second value obtained 3 or more weeks later.

  10. Objective Response Rate (ORR) [ Time Frame: Up to 4.9 years ]
    ORR was defined as the percentage of participants with measurable disease at baseline achieving a complete response (CR) or partial response (PR) according to modified response evaluation criteria in solid tumors (RECIST) criteria. RECIST criteria for CR: disappearance of all target lesions and non-target lesions , any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 millimetre [mm] short axis). PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

  11. Time to Opiate Use for Cancer-related Pain [ Time Frame: Up to 156 weeks ]
    Time to opiate use for cancer-related pain is defined the time interval from the date of randomization to the first date of opiate use for cancer pain.

  12. Time to Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Score by 1 Point [ Time Frame: Up to 156 weeks ]
    Time to deterioration in ECOG Performance Status, the time interval from the date of randomization to the first date in which at least one point change (worsening) in the ECOG is observed during the main study treatment period. The ECOG performance status is a grade scale to measure quality of life (QoL). Scores run from 0 to 5, with 0 denoting perfect health and 5 denoting death.

  13. Overall Survival [ Time Frame: Up to 156 weeks ]
    Overall survival was defined as the time interval from the date of randomization to the date of death from any cause.

  14. Time to Next Prostate Cancer Therapy [ Time Frame: Up to 4.9 years ]
    Time to next prostate cancer therapy is defined as the time interval from the date of randomization to the date of initiation of first next therapy for prostate cancer.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Have a histologically or cytologically confirmed adenocarcinoma of the prostate Have metastatic disease documented by positive bone scan or by computed tomography or magnetic resonance imaging Have prostate cancer progression documented by prostate specific antigen according to Prostate Cancer Working Group 2 or radiographic progression according to modified RECIST (response evaluation criteria in solid tumors, v1.1) criteria Be asymptomatic from prostate cancer. A score of 0-1 on BPI-SF Question #3 (worst pain in last 24 hours) will be considered asymptomatic Be surgically or medically castrated, with testosterone levels of <50 ng/dL (<2.0 nmol/L). If the subject is being treated with luteinizing hormone releasing hormone (LHRH) agonists or antagonists (subjects who have not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to Day 1, Cycle 1 and must be continued throughout the study.

Exclusion Criteria:

Has a history of pituitary or adrenal dysfunction Has an active infection or other medical condition that would contraindicate corticosteroid use Has any chronic medical condition requiring corticosteroid treatment or has received prior corticosteroid treatment for prostate cancer Has a pathological finding consistent with small cell carcinoma of the prostate Has a known brain metastasis


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): NCT01867710


Locations
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Belgium
Aalst, Belgium
Brussels, Belgium
Gent, Belgium
Hasselt, Belgium
Kortrijk, Belgium
Leuven, Belgium
Germany
Hannover, Germany
Mülheim, Germany
Nürtingen, Germany
Tübingen, Germany
Hungary
Budapest, Hungary
Miskolc, Hungary
United Kingdom
Birmingham, United Kingdom
Glasgow, United Kingdom
London, United Kingdom
Sutton, United Kingdom
Whitchurch, United Kingdom
Sponsors and Collaborators
Janssen Pharmaceutica N.V., Belgium

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Janssen Pharmaceutica N.V., Belgium
ClinicalTrials.gov Identifier: NCT01867710    
Other Study ID Numbers: CR100916
2012-004331-23 ( EudraCT Number )
212082PCR2023 ( Other Identifier: Janssen CTMS ID )
First Posted: June 4, 2013    Key Record Dates
Results First Posted: May 11, 2016
Last Update Posted: July 5, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Janssen Pharmaceutica N.V., Belgium:
Mineralocorticoid Excess ; Chemotherapy-Naïve; Metastatic Castration-Resistant Prostate Cancer; Abiraterone Acetate; Zytiga; Prednisone; dexamethasone
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Dexamethasone
Dexamethasone acetate
Prednisone
Abiraterone Acetate
BB 1101
Mineralocorticoids
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Cytochrome P-450 Enzyme Inhibitors