Trial Information

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

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 3 weeks followed by an open-label treatment period of a
maximum of 39 treatment cycles (156 weeks or approximately 3 years). 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 must be completed within 21 days before
patients start taking the study drug. 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 Treatment visit. 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.