Abiraterone With Different Steroid Regimens for Side Effect Related to Mineralcorticoid Excess Prevention in Prostate Cancer Prior to Chemotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Janssen Pharmaceutica N.V., Belgium
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutica N.V., Belgium
ClinicalTrials.gov Identifier:
NCT01867710
First received: May 30, 2013
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

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 (up to a maximum of 5 years after the study starts). 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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Janssen Pharmaceutica N.V., Belgium:

Primary Outcome Measures:
  • Number of participants experiencing neither hypokalemia nor hypertension treatment-emergent adverse events up to Week 24 [ Time Frame: up to 24 Weeks after Day 1 of Cycle 1 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: up to 5 years after the start of study treatment of the first patient in the study ] [ Designated as safety issue: No ]
    time from randomization to the occurrence of one of the following: radiographic progression, clinical progression or death

  • Prostate specific antigen response rate [ Time Frame: up to 5 years after the start of study treatment of the first patient in the study ] [ Designated as safety issue: No ]
    A PSA response is defined as a ≥50% decline from baseline according to the adapted 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.

  • Time to prostate specific antigen progression [ Time Frame: up to 5 years after the start of study treatment of the first patient in the study ] [ Designated as safety issue: No ]
  • Objective response rate [ Time Frame: up to 5 years after the start of study treatment of the first patient in the study ] [ Designated as safety issue: No ]
  • Time to opiate use for cancer pain [ Time Frame: up to end of main study visit at the end of Cycle 39 (156 weeks) ] [ Designated as safety issue: No ]
  • Time to deterioration in Eastern Cooperative Oncology Group (ECOG) performance score by 1 point [ Time Frame: up to end of main study visit at the end of Cycle 39 (156 weeks) ] [ Designated as safety issue: No ]
  • Number of participants with change in EQ-5D-5L score [ Time Frame: Day 1 of Cycles 1, 6, 18, 39 or at end of main study treatment assessment for participants discontinuing study treatment Cycle 39 ] [ Designated as safety issue: No ]
  • Number of participants with change in Brief Pain Inventory - short form (BPI-SF) score [ Time Frame: Screening; Day 1 of Cycles 1, 6, 18, 39 or at end of main study treatment assessment for participants discontinuing study treatment Cycle 39 ] [ Designated as safety issue: No ]
  • Number of participants with change in Functional Assessment of Cancer Therapy - Prostate Cancer (FACT-P) score [ Time Frame: Day 1 of Cycles 1, 6, 18, 39 or at end of main study treatment assessment for participants discontinuing study treatment Cycle 39 ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: up to 5 years after the start of study treatment of the first patient in the study ] [ Designated as safety issue: No ]
  • Time to next therapy for prostate cancer [ Time Frame: up to 5 years after the start of study treatment of the first patient in the study ] [ Designated as safety issue: No ]
  • Time to initiation of subsequent chemotherapy [ Time Frame: up to 5 years after the start of study treatment of the first patient in the study ] [ Designated as safety issue: No ]
  • Treatment duration of subsequent chemotherapy [ Time Frame: up to 5 years after the start of study treatment of the first patient in the study ] [ Designated as safety issue: No ]

Estimated Enrollment: 144
Study Start Date: July 2013
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Hide Detailed Description

Detailed Description:

This is a randomized (study drug is assigned by chance), open-label (all people know the identity of the intervention), parallel-arm, multicenter, phase 2 study of treatment with abiraterone acetate (AA) and 4 alternative steroid treatment strategies in asymptomatic, chemotherapy-naïve, mCRPC patients. A target of 144 patients will be enrolled in this study with 36 patients planned per treatment arm. All patients participating in this study will receive abiraterone acetate. All patients will also take either prednisone or dexamethasone. Patients will receive abiraterone acetate along with either prednisone at one of three different dose schedules or with dexamethasone at one dose schedule. Patients may also be asked to take a medication to protect from osteoporosis as this can be increased by long term use of corticosteroids. There are 4 treatment groups in this study: (a) Four 250mg tablets of abiraterone acetate taken together once daily and one 2.5 mg tablet of prednisone taken twice daily; (b) Four 250mg tablets of abiraterone acetate taken together once daily and one 5 mg tablet of prednisone taken once daily; (c) Four 250mg tablets of abiraterone acetate taken together once daily and one 5 mg tablet of prednisone taken twice daily; (d) Four 250mg tablets of abiraterone acetate taken together once daily and one 0.5 mg tablet of dexamethasone taken once daily. The chance that patients will get prednisone is 3 out of 4 patients. The chance that they will get dexamethasone is 1 out of 4 patients. Abiraterone acetate, prednisone and dexamethasone will be considered as study drugs. The main study will consist of a screening phase of 4 weeks followed by an open-label treatment period of a maximum of 39 treatment cycles (156 weeks or approximately 3 years). The main study treatment period cut-off date will be 156 weeks after the start of study treatment for the first patient participating in the study. Patients will participate in the main study treatment period until the cut-off date, and will receive study treatment until radiographic disease progression and/or unequivocal clinical progression and/or other specific reasons for discontinuation of treatment. Patients will be asked if they would be willing to participate in a follow-up or extension phase of the study for a maximum of 5 years after the study starts. The amount of time patients will be in the study will vary depending when they join the study and time remaining to the study end date and on their response to the treatment. Patients may come off the study drug if their cancer worsens, if they are unable to tolerate the study treatment, if their doctor determines that they should begin another cancer treatment, or if they decide to withdraw consent. A treatment "cycle" in this study is the amount of time a patient will be asked to take the study medication, and have regularly pre-scheduled checkups and laboratory assessments. Each treatment-cycle will last 28 days. There are a maximum of 39 treatment cycles in this study (over a period of 156 weeks). If patients enter the extension phase, they will be asked to attend hospital every 12 weeks for the remaining time that they stay on the study. Other anticancer therapy or immunotherapy must be ended before and while participating in this clinical study with abiraterone acetate. Also some medications are not allowed during the study. For example, if patients are receiving a steroid other than prednisone, it will be necessary to switch it to prednisone or dexamethasone, depending on to which treatment group patients have been assigned, for the duration of the study. If needed, their study doctor may slowly decrease and stop some or all of their current medicines before the study treatment starts. This is called washout. Do not stop taking any of their current medicine unless their study doctor tells patients to do so. At screening the study doctor will first check that patients are qualified. Screening procedures will be conducted within 4 weeks before randomization. During the main study treatment phase patients will come to the study clinic for Study Visits about 21 times in total (including for screening) if they stay on treatment for 39 cycles. During Cycle 1 of this study, patients will be asked to come to the clinic three times for assessments: on Day 1 which also will usually be their first day of treatment, Day 15 and two weeks later. After that patients will need to return to the clinic once every four weeks for the first 6 months. After that, the visits are once every 3 months for assessments. In addition, patients will need to visit either the clinic or the Outpatients every 2 weeks for the first 3 months and every 4 weeks after that to the end of their treatment to provide a small quantity of blood for testing. If patients either continue study treatment to 39 cycles, or if patients discontinue from the study before 39 treatment cycles, their last visit with drug dispensed will be called an End-of-main-study-treatment (EOMT) visit. EOMT assessments will be performed for all patients who started study treatment, either at the cut-off date or when they discontinue before the cut-off date. Additionally, for patients discontinuing study treatment before the cut-off date, an end-of-main-study (EOMS) visit will be performed 4 weeks after study medication is stopped. Patients will also be required to return to the study site 4 weeks after their last treatment for the "End of Main Study" visit as below. This visit is for some routine study assessments. During the extension phase, patients will be provided with study drug outside of the main study for up to a maximum of 5 years after the study starts. During this phase, patients will receive study drug during their 12 weekly visits and their doctor will check on their health status at the same time. Patients will not be required to provide blood or urine samples during this phase. Patients are likely to be eligible to join this extension phase if patients have responded well to the study drug and have not been discontinued from the main study. Also even if they have discontinued from the main study, if they have had no disease progression their doctor may advise them that they are eligible to join this phase. Their last visit will be called an End of Extension visit. For this visit, patients will be required to return to the study site 4 weeks after their last treatment for some final assessments. Follow-Up: Following discontinuation of study treatment at any time during the study, for any reason other than withdrawal of consent, survival and subsequent prostate cancer therapies will be monitored until 5 years after the start of study treatment of the first patient participating in the study. This information will be obtained by 6-monthly telephone contact and/or chart review, with a source data verification visit scheduled after the death of the patient or at the end of the study. Their doctor may phone them or their family to ask about their health status during this 5 year period if he/she feels that their chart records may need to be updated. A Scientific Advisory Committee will be commissioned to ensure scientific validity of this study, to identify any scientifically relevant trends, and to provide recommendations to the sponsor.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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

  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: NCT01867710

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

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

Additional Information:
No publications provided

Responsible Party: Janssen Pharmaceutica N.V., Belgium
ClinicalTrials.gov Identifier: NCT01867710     History of Changes
Other Study ID Numbers: CR100916, 2012-004331-23, 212082PCR2023
Study First Received: May 30, 2013
Last Updated: July 24, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Ethics Commission
Great Britain: Medicines and Healthcare Products Regulatory Agency
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines

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:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Dexamethasone acetate
Dexamethasone
Prednisone
Dexamethasone 21-phosphate
BB 1101
Mineralocorticoids
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 01, 2014