Enzalutamide in Androgen Deprivation Therapy With Radiation Therapy for High Risk, Clinically Localised, Prostate Cancer (ENZARAD)
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| ClinicalTrials.gov Identifier: NCT02446444 |
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Recruitment Status :
Active, not recruiting
First Posted : May 18, 2015
Last Update Posted : December 19, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Prostatic Neoplasms | Drug: Enzalutamide Drug: Conventional NSAA Drug: LHRHA Radiation: External Beam Radiotherapy (78 Gy in 39 fractions or 46 Gy in 23 fractions plus brachytherapy boost) | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 802 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Stratification Factors:
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| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Randomised Phase 3 Trial of Enzalutamide in Androgen Deprivation Therapy With Radiation Therapy for High Risk, Clinically Localised, Prostate Cancer: ENZARAD |
| Study Start Date : | March 2014 |
| Estimated Primary Completion Date : | December 2024 |
| Estimated Study Completion Date : | December 2025 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Enzalutamide
Enzalutamide 160 mg daily, by mouth, for 24 months from randomisation. All participants are treated with a LHRHA for 24 months from randomisation and external beam radiation therapy started approximately 16 weeks after randomisation (+/- brachytherapy boost)
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Drug: Enzalutamide Drug: LHRHA Radiation: External Beam Radiotherapy (78 Gy in 39 fractions or 46 Gy in 23 fractions plus brachytherapy boost) |
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Active Comparator: Conventional Non-steroidal Anti-androgen (NSAA)
Conventional Non-steroidal Anti-androgen (NSAA), by mouth, for 6 months from randomisation. All participants are treated with a LHRHA for 24 months from randomisation and external beam radiation therapy started approximately 16 weeks after randomisation (+/- brachytherapy boost) |
Drug: Conventional NSAA Drug: LHRHA Radiation: External Beam Radiotherapy (78 Gy in 39 fractions or 46 Gy in 23 fractions plus brachytherapy boost) |
- Metastasis-free survival [ Time Frame: 5 years ]
Metastasis free survival (MFS) is defined as the interval from the date of randomisation to the date of first evidence of metastasis or death from any cause, whichever occurs first, or the date of last known follow-up alive and without metastases.
Evidence of metastasis includes findings on whole body bone scan (WBBS) or CT or MRI that are either characteristic of metastatic prostate cancer, and/or confirmed by other test results, e.g. cytology or histopathology, and lesion qualifies as new metastatic disease per RECIST 1.1. Detection of metastasis by other modalities, eg Ga-68 PSMA (Prostate Specific Membrane Antigen) PET, does not constitute an event unless confirmed by WBBS or CT or MR
- Overall survival [ Time Frame: 5 years ]Overall survival (OS) is defined as the interval from the date of randomisation to date of death from any cause, or the date of last known follow-up alive.
- Prostate cancer-specific survival [ Time Frame: 5 years ]Prostate cancer-specific survival is defined as the interval from the date of randomisation to the date of death from prostate cancer, or the date of last known follow-up alive.
- PSA (Prostate-Specific Antigen) progression-free survival [ Time Frame: 5 years ]
PSA progression-free survival is defined as the interval from the date of randomisation to the date of first evidence of PSA progression, clinical progression, or death from any cause, whichever occurs first, or the date of last known follow-up without PSA progression and without clinical progression.
PSA progression as defined by the Phoenix criteria: an increase in PSA of more than 2ng/mL above the nadir (lowest) PSA level.
- Clinical progression-free survival [ Time Frame: 5 years ]
Clinical progression-free survival is defined as the interval from the date of randomisation to the date of first clinical evidence of disease progression or death from any cause, whichever occurs first, or the date of last known follow-up alive without clinical progression.
Clinical evidence of disease progression includes evidence of progression or recurrence on imaging, clinical examination, development of symptoms attributable to cancer progression, or initiation of other anticancer treatment for prostate cancer.
- Time to subsequent hormonal therapy [ Time Frame: 5 years ]Time to subsequent hormone therapy is the interval from randomisation to the first date that androgen deprivation therapy is recommenced for the treatment of recurrent (or progressive) prostate cancer, or the date of last known follow-up without recommencement of androgen deprivation therapy.
- Time to castration-resistant disease (PCWG2 criteria) [ Time Frame: 5 years ]Castration resistant prostate cancer (CRPC) is defined, per PCWG2, by a rising PSA that is greater than 2ng/mL higher than the most recent nadir with a testosterone < 50 ng/dL (<1.7 nmol/L); the rise has to be at least 25% over the most recent nadir; and, the rise has to be confirmed by a second PSA at least three weeks later. The time to castration-resistant prostate cancer is defined as the interval from randomisation to the date that the PSA first met the criteria defined above (i.e. the date of the first PSA to meet these criteria, not the date of the subsequent confirmatory test), or the date of last known follow-up without CRPC.
- Safety (adverse events - CTCAE v4.03) [ Time Frame: 5 years ]The NCI Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) will be used to classify and grade the intensity of adverse events occurring until 30 days after the last dose of study treatment.
- Health related quality of life (HRQL) [ Time Frame: 5 years ]HRQL will be reported by participants using the EORTC core quality of life questionnaire (QLQ C-30) and prostate cancer specific module (PR-25). The EQ-5D-5L will be used to derive utility scores suitable for quality adjusted survival analyses
- Health outcomes relative to costs (incremental cost effectiveness ratio) [ Time Frame: 5 years ]Information on the following areas of health-care resource usage will be collected: hospitalisations, visits to health professionals, and medications. Quality-adjusted survival (QAS) time will be used to quantify the incremental effectiveness of adding enzalutamide to standard treatment.
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.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
Men with localised prostate cancer at high risk for recurrence deemed suitable for external beam radiation therapy.
Inclusion Criteria:
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Pathological diagnosis of adenocarcinoma of the prostate, judged to be at high risk for recurrence based on any of the following (in accordance with the International Society of Urological Pathology (ISUP) Consensus 2005:
Gleason score 8-10 OR Gleason score of 4+3 AND clinical T2b-4 AND PSA >20ng/mL OR N1 disease (involvement of lymph nodes at or below the bifurcation of the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or biopsy proven
- Age ≥18 years
- Adequate bone marrow function Haemoglobin (Hb) ≥100g/L and White Cell Count (WCC) ≥ 4.0 x 109/L and platelets ≥100 x 109/L
- Adequate liver function: Alanine transaminase (ALT) < 2 x ULN and bilirubin < 1.5 x Upper Limit of Normal (ULN), (or if bilirubin is between 1.5 - 2 x ULN, they must have a normal conjugated bilirubin).
- Adequate renal function: calculated creatinine clearance > 30 ml/min (Cockcroft-Gault)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Study treatment both planned and able to start within 7 days of randomisation.
- Willing and able to comply with all study requirements, including treatment, and attending required assessments
- Has completed the baseline HRQOL questionnaires UNLESS is unable to complete because of literacy or limited vision
- Signed, written, informed consent
Exclusion Criteria:
- Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
- Involvement of lymph nodes superior to the common iliac bifurcation, and/or outside the pelvis (distant lymph nodes). Lymph node involvement is defined by histopathological confirmation, or by a short axis measurement >10mm on standard imaging (CT or MRI, but not PET).
- Any contraindication to external beam radiotherapy
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History of
- seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma).
- loss of consciousness or transient ischemic attack within 12 months of randomization
- significant cardiovascular disease within the last 3 months: including myocardial infarction, unstable angina, congestive heart failure (NYHA grade II or greater), ongoing arrhythmias of Grade > 2 , thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
- Evidence of metastatic disease: minimum imaging required Computed tomography scan (CT) / Magnetic Resonance Imaging (MRI) of the abdomen and pelvis, and Whole Body Bone Scan (WBBS). If equivocal bone scan, follow-up plain films are required to show NO evidence of cancer if not covered by CT/MRI
- PSA > 100 ng/mL
- History of another malignancy within 5 years prior to randomisation except for non-melanomatous carcinoma of the skin; or, adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (i.e. Tis, Ta and low grade T1 tumours).
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Concurrent illness, including severe infection that might jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
- Human Immunodeficiency Virus (HIV)-infection is not an exclusion criterion if it is controlled with anti-retroviral drugs that are unaffected by concomitant enzalutamide.
- 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;
- Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception.
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Use of hormonal therapy or androgen deprivation therapy, including enzalutamide, except in the following setting:
- Use of LHRHA (with or without anti-androgens) for less than 30 days prior to randomisation in the trial.
- Bilateral orchidectomy or radical prostatectomy
- Prior brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields
- Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases.
- Major surgery within 21 days prior to randomisation
- Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of enzalutamide, including difficulty swallowing tablets
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): NCT02446444
Show 69 study locations
| Study Chair: | Scott Williams | ANZUP and Peter MacCallum Cancer Centre | |
| Study Chair: | Paul Nguyen | Dana Farber Cancer Institute and ANZUP |
| Responsible Party: | University of Sydney |
| ClinicalTrials.gov Identifier: | NCT02446444 |
| Other Study ID Numbers: |
ANZUP1303 ACTRN12614000126617 ( Other Identifier: Australian New Zealand Clinical Trials Registry (ANZCTR) ) |
| First Posted: | May 18, 2015 Key Record Dates |
| Last Update Posted: | December 19, 2022 |
| Last Verified: | December 2022 |
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High risk clinically localised prostate cancer |
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Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms |
Genital Diseases, Male Genital Diseases Urogenital Diseases Prostatic Diseases Male Urogenital Diseases |