None listed
Conditions
Brief summary
Participants are invited to take part in this research study to test a new treatment combination for prostate cancer. This is because they have cancer that started in the prostate and has spread to other parts of their body. This is known as metastatic prostate cancer. Current treatment for newly diagnosed metastatic prostate cancer involves androgen deprivation therapy(ADT). Androgen deprivation therapy has two components: 1. The main component is by stopping the release of androgen from the testicles. This is mainly done by using drugs that prevent the testicles from making androgens, and therefore reducing the levels of androgens in the body to low levels. These drugs are called luteinising hormone releasing hormone analogues (LHRHA). These drugs are given as injections. This is usually part of the standard initial treatment for men in your situation. The other way of reducing androgen production by the testicles is with a surgical operation to remove both testicles. This is not part of the trial. If participants have already had this surgical procedure or it is planned to be done, they will not need to be on LHRHA, but can still take part in this study. 2. The second component of ADT is to block the effects of androgens produced in other parts of the body with antiandrogen drugs. Antiandrogen drugs block testosterone and related androgens from attaching to molecules in the cancer cell called 'androgen receptors'. Blocking this attachment prevents androgens from having their effect. This might provide additional benefit in treating the cancer although this has not yet been proven. Several different types of antiandrogen drugs are available for use already. Enzalutamide is a new antiandrogen that is not yet approved for use in Australia. This study will compare the effectiveness of enzalutamide versus the currently available antiandrogen drugs when used on a background of treatment with a LHRHA (or surgical removal of the testicles). The main aim of the study is to see which of these combinations is best at improving the survival of men in this situation. Recent studies show promising results with the use of enzalutamide in participants who had been treated with androgen deprivation therapy and were no longer responding to the standard antiandrogens, this is known as castrate resistant prostate cancer (CRPC), which is a more advanced stage than the type of metastatic prostate cancer being studied here. With this stage of metastatic prostate cancer there is no evidence yet on which treatment is best to treat it. To do this, a total of 1100 participants will participate where half the participants on the study will receive enzalutamide with a LHRHA or surgical operation to remove both testicles and the other half (550 participants) will receive already available antiandrogens (but not enzalutamide) with a LHRHA or surgical operation to remove testicles. All participants on this study will receive active therapy and no placebo treatment will be used. The study is open label, meaning that both the participants and the investigators will know the treatment the participant will receive.
Interventions
Arm 1 - Enzalutamide 160mg daily by mouth, until disease progression or prohibitive toxicity, adherence monitored by drug tablet return.
Sponsors
NHMRC Clinical Trials Centre (CTC), University of Sydney
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male aged 18 or older with metastatic adenocarcinoma of the prostate defined by a) Documented histopathology or cytopathology of prostate adenocarcinoma from a biopsy of a metastatic site OR b) Documented histopathology of prostate adenocarcinoma from a TRUS biopsy, radical prostatectomy, or TURP and metastatic disease consistent with prostate cancer. OR c) Metastatic disease typical of prostate cancer (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes) AND a serum concentration of PSA that is rising and >20ng/mL 2. Target or non-target lesions according to RECIST 1.1 3. Adequate bone marrow function: Hb =100g/L and WCC = 4.0 x 109/L and platelets =100 x 109/L. 4. Adequate liver function: ALT < 2 x ULN and bilirubin < 1.5 x ULN, (or if bilirubin is between 1.5-2x ULN, they must have a normal conjugated bilirubin). If liver metastases are present ALT must be < 5xULN 5. Adequate renal function: calculated creatinine clearance > 30 ml/min (Cockroft-Gault,) 6. ECOG performance status of 0-2. Patients with performance status 2 are only eligible if the decline in performance status is due to metastatic prostate cancer. 7. Study treatment both planned and able to start within 7 days after randomisation. 8. Willing and able to comply with all study requirements, including treatment and required assessments 9. Has completed baseline HRQL questionnaires UNLESS is unable to complete because of limited literacy or vision 10. Signed, written, informed consent
Exclusion criteria
1. Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components 2. History of: a. seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma). b. loss of consciousness or transient ischemic attack within 12 months of randomization c. significant cardiovascular disease within the last 3 months including: myocardial infarction, unstable angina, congestive heart failure (NYHA functional capacity class II or greater), ongoing arrhythmias of Grade >2 [CTCAE, version 4.03], thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed. 3. Life expectancy of less than 12 months. 4. History of another malignancy within 5 years prior to randomisation, except for either non- melanomatous carcinoma of the skin or, adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (Tis, Ta and low grade T1 tumours). 5. Concurrent illness, including severe infection that might jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety a. HIV-infection is not an exclusion criterion if it is controlled with anti-retroviral drugs that are unaffected by concomitant enzalutamide. 6. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse; 7. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception. 8. Prior ADT for prostate cancer (including bilateral orchidectomy), except in the following settings: a. Started less than 12 weeks prior to randomisation AND PSA is stable or falling. The 12 weeks starts from whichever of the following occurs earliest: first dose of oral anti- androgen, LHRHA, or surgical castration. b. In the adjuvant setting, where the completion of adjuvant hormonal therapy was more than 12 months prior to randomisation AND the total duration of hormonal treatment did not exceed 24 months. For depot preparations, hormonal therapy is deemed to have started with the first dose and to have been completed when the next dose would otherwise have been due, e.g. 12 weeks after the last dose of depot goserelin 10.8mg. 9. Prior cytotoxic chemotherapy for prostate cancer, but up to 2 cycles of docetaxel chemotherapy for metastatic disease is permitted.as per section 5.3.2.4 is allowed. 10. Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases.
Outcome results
None listed