Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer (ENZAMET)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02446405
Recruitment Status : Active, not recruiting
First Posted : May 18, 2015
Last Update Posted : May 3, 2018
Sponsor:
Collaborators:
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
National Health and Medical Research Council, Australia
Cancer Trials Ireland
NCIC Clinical Trials Group
Information provided by (Responsible Party):
University of Sydney

Tracking Information
First Submitted Date  ICMJE May 4, 2015
First Posted Date  ICMJE May 18, 2015
Last Update Posted Date May 3, 2018
Study Start Date  ICMJE March 2014
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 13, 2015)
Overall Survival Time [ Time Frame: 3 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02446405 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2015)
  • Prostate specific antigen progression free survival time [ Time Frame: 3 years ]
  • Clinical progression free survival time [ Time Frame: 3 years ]
  • Adverse events [ Time Frame: 3 years ]
  • Health-related quality of life (EORTC Core Quality of Life Questionnaire (QLQ C-30), Quality of Life Questionnaire for Prostate Cancer (PR-25), Euroqol 5 item preference-based measure of health (EQ-5 D-5L)) [ Time Frame: 3 years ]
  • Healthcare resource cost-effectiveness (incremental cost effectiveness ratio) [ Time Frame: 3 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2015)
  • Prostate specific antigen progression free survival time [ Time Frame: 3 years ]
  • Clinical progression free survival time [ Time Frame: 3 years ]
  • Adverse events [ Time Frame: 3 years ]
  • Health-related quality of life (EORTC Core Quality of Life Questionnaire (QLQ C-30), Quality of Life Questionnaire for Prostate Cancer (PR-25), Euroqol 5 item preference-based measure of health (EQ-5 D-5L)) [ Time Frame: 3 years ]
  • Healthcare resource cost-effectiveness [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer
Official Title  ICMJE Randomised Phase 3 Trial of Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer: ENZAMET
Brief Summary The purpose of this study is to determine the effectiveness of enzalutamide, versus a conventional non-steroidal anti androgen (NSAA), when combined with a luteinizing hormone releasing hormone analog (LHRHA) or surgical castration, as first line androgen deprivation therapy (ADT) for newly diagnosed metastatic prostate cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Stratification factors:

  1. High volume disease (yes versus no), characterised as:

    • 4 or more bone metastases, one of which is outside the vertebral column and pelvis AND/OR
    • Visceral metastases (e.g. lung, pleura, liver, adrenal and others) Lymph node involvement or bladder invasion do NOT qualify as visceral disease.
  2. Study site
  3. Concomitant "anti-resorptive" therapy to delay skeletal related events when commencing ADT
  4. Co-morbidities according to the Adult Co-morbidity Evaluation (ACE-27: 0-1 vs 2-3)
  5. Early use of docetaxel defined as use of docetaxel in conjunction with initiation of ADT.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostatic Neoplasms
Intervention  ICMJE
  • Drug: Enzalutamide
  • Drug: NSAA
  • Drug: LHRHA or Surgical Castration
Study Arms  ICMJE
  • Experimental: Enzalutamide

    Enzalutamide is 160 mg daily, by mouth, until clinical disease progression or prohibitive toxicity.

    All participants are to receive standard background therapy with a LHRHA or surgical castration, as per standard of care. The choice of the LHRHA or surgical castration is at the discretion of the treating clinician.

    Interventions:
    • Drug: Enzalutamide
    • Drug: LHRHA or Surgical Castration
  • Active Comparator: Conventional NSAA

    Conventional NSAA, by mouth until clinical disease progression or prohibitive toxicity.

    All participants are to receive standard background therapy with a LHRHA or surgical castration, as per standard of care. The choice of the LHRHA or surgical castration is at the discretion of the treating clinician.

    Interventions:
    • Drug: NSAA
    • Drug: LHRHA or Surgical Castration
Publications * Davis ID. Answering Questions and Questioning Answers: More Evidence To Guide Decision-making About Chemohormonal Therapy in Metastatic Prostate Cancer. Eur Urol. 2018 Jun;73(6):856-858. doi: 10.1016/j.eururo.2018.02.020. Epub 2018 Mar 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 26, 2017)
1125
Original Estimated Enrollment  ICMJE
 (submitted: May 13, 2015)
1100
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Men starting first line androgen deprivation therapy for metastatic prostate cancer.

Inclusion criteria:

  1. Male aged 18 or older with metastatic adenocarcinoma of the prostate
  2. Target or non-target lesions according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1
  3. Adequate bone marrow function: Haemoglobin (Hb) ≥100g/L and White Cell Count (WCC) ≥ 4.0 x 109/L and platelets ≥100 x 109/L.
  4. Adequate liver function: Alanine transaminase (ALT) < 2 x Upper Limit of Normal (ULN) and bilirubin < 1.5 x ULN, (or if bilirubin is between 1.5-2 x ULN, they must have a normal conjugated bilirubin). If liver metastases are present ALT must be < 5 x ULN
  5. Adequate renal function: calculated creatinine clearance > 30 ml/min (Cockcroft-Gault)
  6. Eastern Cooperative Oncology Group (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 Health-Related Quality of Life (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

    • 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, ongoing arrhythmias of Grade >2 [National Cancer Institute Common Terminology Criteria for Adverse Events (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. Human Immunodeficiency Virus (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:

    • Started less than 12 weeks prior to randomisation AND Prostate Specific Antigen (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.
    • 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.
  10. Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Ireland,   New Zealand,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02446405
Other Study ID Numbers  ICMJE ANZUP 1304
ACTRN12614000110684 ( Other Identifier: Australian New Zealand Clinical Trials Registry (ANZCTR) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Sydney
Study Sponsor  ICMJE University of Sydney
Collaborators  ICMJE
  • Australian and New Zealand Urogenital and Prostate Cancer Trials Group
  • National Health and Medical Research Council, Australia
  • Cancer Trials Ireland
  • NCIC Clinical Trials Group
Investigators  ICMJE
Study Chair: Christopher Sweeney Dana Farber Cancer Institute and ANZUP
Study Chair: Ian Davis ANZUP and Eastern Health Box Hill Hospital
PRS Account University of Sydney
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP