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

Janssen Pharmaceutica N.V., Belgium164 enrolled

Overview

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.

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 250 mg tablets of abiraterone acetate taken together once daily and one 2.5 mg tablet of prednisone taken twice daily; (b) Four 250 mg 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 250 mg 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 approximately 4.5 years after the start of study treatment of the first subject participating in the study. 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 approximately 4.5 years after the start of study treatment of the first subject participating in the study. 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 approximately 4.5 years after the start of study treatment of the first subject 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 approximately 4.5 years of 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.

Outcomes

Primary Outcomes

Percentage of Participants Experiencing Neither of the 2 Mineralocorticoid Excess Toxicity During the First 24 Weeks of Treatment

No mineralocorticoid excess is defined as experiencing neither of the 2 mineralocorticoid excess toxicities, that is, neither hypokalemia nor hypertension.

Time frame: Week 24

Secondary Outcomes

Percentage of Participants With Confirmed Prostate Specific Antigen (PSA) Response Rate [Greater Than or Equal to (>=) 50 Percent (%) Decline From Baseline] at 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.

Time frame: Week 12

Change From Baseline to Endpoint in Brief Pain Inventory- Short Form (BPI-SF) Score: Worst Pain

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.

Time frame: Baseline up to the Endpoint (last post-baseline assessment value during 156 weeks of main study treatment period [MSTP])

Change From Baseline to Endpoint in Brief Pain Inventory- Short Form (BPI-SF) Score: Pain Intensity Subscale

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.