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Darolutamide Augments Standard Therapy for Localised Very High-Risk Cancer of the Prostate (DASL-HiCaP)

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ClinicalTrials.gov Identifier: NCT04136353
Recruitment Status : Not yet recruiting
First Posted : October 23, 2019
Last Update Posted : October 23, 2019
Sponsor:
Collaborators:
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Bayer
Cancer Trials Ireland
Canadian Cancer Trials Group
Information provided by (Responsible Party):
University of Sydney

Brief Summary:
The purpose of this study is to determine the effectiveness of darolutamide as part of adjuvant androgen deprivation therapy (ADT) with a luteinising hormone releasing hormone analogue (LHRHA) in men having radiation therapy for localised prostate cancer at very high risk of recurrence.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Darolutamide Drug: Placebo oral tablet Drug: Luteinizing Hormone-Releasing Hormone Analog Radiation: External Beam Radiotherapy Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: DASL-HiCaP: Darolutamide Augments Standard Therapy for Localised Very High-Risk Cancer of the Prostate (ANZUP1801): A Randomised Phase 3 Double-blind, Placebo-controlled Trial of Adding Darolutamide to Androgen Deprivation Therapy and Definitive or Salvage Radiation in Very High Risk, Clinically Localised Prostate Cancer
Estimated Study Start Date : January 31, 2020
Estimated Primary Completion Date : January 31, 2028
Estimated Study Completion Date : July 31, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Darolutamide

Darolutamide 600mg (2 x 300mg tablets) twice daily by mouth for 96 weeks, adherence monitored by participant report.

All participants are treated with an LHRHA for 96 weeks from randomisation and external beam radiation therapy started within 8-24 weeks after randomisation.

Drug: Darolutamide
2 x 300mg oral tablets twice daily for 96 weeks

Drug: Luteinizing Hormone-Releasing Hormone Analog
All participants are to receive standard background therapy with an LHRHA, as per standard of care. The choice of LHRHA is at the discretion of the treating clinician.

Radiation: External Beam Radiotherapy
All participants are to receive standard background therapy with curative-intent RT to the prostate or prostate bed as well as the pelvic lymph nodes using EBRT.

Placebo Comparator: Placebo

Placebo (2 tablets) twice daily by mouth for 96 weeks, adherence monitored by participant report.

All participants are treated with an LHRHA for 96 weeks from randomisation and external beam radiation therapy started within 8-24 weeks after randomisation.

Drug: Placebo oral tablet
2 oral tablets twice daily for 96 weeks

Drug: Luteinizing Hormone-Releasing Hormone Analog
All participants are to receive standard background therapy with an LHRHA, as per standard of care. The choice of LHRHA is at the discretion of the treating clinician.

Radiation: External Beam Radiotherapy
All participants are to receive standard background therapy with curative-intent RT to the prostate or prostate bed as well as the pelvic lymph nodes using EBRT.




Primary Outcome Measures :
  1. Metastasis-free survival [ Time Frame: Through study completion, an average of 5 years ]
    Evidence of metastases includes findings on WBBS or CT or MRI (as reported by the site investigator) that are either characteristic of metastatic prostate cancer, and/or confirmed by other test results e.g. cytology or histopathology.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Through study completion, an average of 5 years ]
  2. Prostate cancer-specific survival [ Time Frame: Through study completion, an average of 5 years ]
  3. PSA-progression free survival [ Time Frame: Through study completion, an average of 5 years ]
    For participants who receive definitive radiotherapy (i.e. without radical prostatectomy), PSA progression is defined by the Phoenix criteria (requires confirmation by a repeat PSA performed at least 3 weeks later). For participants who have undergone a radical prostatectomy, an increase in PSA of >0.2 ng/mL above the nadir would be considered PSA progression (requires confirmation by a repeat PSA performed at least 3 weeks later).

  4. Time to subsequent hormonal therapy [ Time Frame: Through study completion, an average of 5 years ]
  5. Time to castration-resistance [ Time Frame: Through study completion, an average of 5 years ]
    Defined according to the PCWG3 criteria. If a participant has radiographic progression without serological progression, this will also be deemed castration resistant prostate cancer

  6. Frequency and severity of adverse events (CTCAE V5.0) [ Time Frame: Approximately 12-weekly for 2 years from randomisation until 30 days after the last dose of study treatment. ]
  7. Health-related quality of life [ Time Frame: Through study completion, an average of 5 years ]
    EORTC Core Quality of Life Questionnaire (QLQC-30). Importance of quality of life issues are assessed using a four-point scale (1 = not at all, 4 = very much)

  8. Health-related quality of life [ Time Frame: Through study completion, an average of 5 years ]
    EORTC Quality of Life Questionnaire for Prostate Cancer (PR-25). Importance of quality of life issues are assessed using a four-point scale (1 = not at all, 4 = very much)

  9. Health-related quality of life [ Time Frame: Through study completion, an average of 5 years ]
    Euroqol 5 item preference-based measure of health (EQ-5D-5L), comprising 5 questions with a score from 1 to 5 each and a visual analogue scale from 0 to 100.

  10. Fear of cancer recurrence [ Time Frame: Through study completion, an average of 5 years ]
    Using the Fear of Cancer Recurrence Inventory (FCRI), a 42-item questionnaire with scores of 0 (never/not at all) - 4 (all the time/a great deal) for each.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men aged 18 years and older, with pathological diagnosis of adenocarcinoma of the prostate
  2. EITHER planned for primary RT and judged to be at very high risk for recurrence based on any of the following:

    • Grade Group 5, OR
    • Grade Group 4 AND one or more of the following: clinical T2b-4 OR MRI with seminal vesicle invasion OR extracapsular extension OR PSA > 20ng/mL, OR
    • Pelvic nodal involvement (involvement of lymph nodes (LNs) 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 pathologically confirmed (PSMA PET alone is not considered enough if < 10mm)

    OR Post-radical prostatectomy ≤ 365 days prior to randomisation and planned for RT with persistent PSA (≥ 0.1 ng/mL which has not fallen on two occasions at least one week apart) or rising PSA (PSA > 0.1 ng/mL and rising on two occasions at least one week apart) judged to be at very high risk for recurrence based on any of the following:

    • Grade Group 5, OR
    • Grade Group 4 AND pT3a or higher, OR
    • Pelvic nodal involvement (involvement of LNs 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 pathologically confirmed (PSMA PET alone is not considered enough if ≤ 10mm)
  3. Adequate bone marrow function: Haemoglobin ≥ 100g/L, white cell count (WCC) ≥ 4.0x10^9/L, absolute neutrophil count (ANC) ≥ 1.5x10^9/L and platelets > 100 x 10^9/L
  4. Adequate liver function: alanine aminotransferase (ALT) < 2 x upper limit of normal (ULN) and total bilirubin < 1.5 x ULN, (or if total bilirubin is between 1.5 - 2 x ULN, they must have a normal conjugated bilirubin)
  5. Adequate renal function: calculated creatinine clearance > 30 mL/min (Cockroft-Gault)
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
  7. Study treatment both planned and able to start within 7 days after randomisation
  8. Willing to complete health-related quality of life (HRQL) questionnaires UNLESS is unable to complete because of literacy or limited vision
  9. Willing and able to comply with all study requirements, including standard of care treatment such as EBRT, timing and/or nature of required assessments
  10. Signed, written informed consent

    Exclusion Criteria:

  11. Prostate cancer with predominant non-adenocarcinoma features (sarcomatoid or spindle cell or neuroendocrine small cell or squamous cell components or other non-adenocarcinoma)
  12. Involvement of LNs by conventional CT imaging superior to the common iliac artery bifurcation, and/or outside the pelvis (distant LNs). LN involvement is defined by histopathological confirmation, or by a short axis measurement >10mm on standard imaging (CT or MRI, but not PET).
  13. Evidence of metastatic disease per RECIST criteria: the minimum imaging required is a CT and/or MRI of the abdomen and pelvis, and a whole body radioisotope 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. If PSMA PET shows disease beyond the pelvic LN not seen on conventional imaging per RECIST, the patient is still eligible.
  14. PSA > 100 ng/mL
  15. Any prior use of new generation potent androgen receptor inhibition (abiraterone, enzalutamide, apalutamide, darolutamide or similar agents).
  16. Prior ADT except the following, which are allowed:

    • Prior androgen deprivation commenced within 90 days prior to randomisation as long as it is limited to: (i) LHRHA, or (ii) low potency nonsteroidal antiandrogen (NSAA) (e.g bicalutamide, flutamide, nilutamide);
    • Any prior use of 5-alpha reductase inhibitor
  17. Bilateral orchidectomy
  18. Prior pelvic brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields that would preclude the required RT
  19. History of

    • Loss of consciousness or transient ischemic attack within 3 months prior to randomisation, or
    • Significant cardiovascular disease within 3 months prior to randomisation: including myocardial infarction, unstable angina, congestive heart failure (NYHA grade II or greater), ongoing arrhythmias of Grade > 2 (CTCAE v5.0), thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
  20. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of darolutamide, including difficulty swallowing tablets
  21. History of another malignancy within 5 years prior to randomisation except for those malignancies treated with curative intent with a predicted risk of relapse of less than 10% including but not limited to non-melanoma carcinoma of the skin; or adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (i.e. Tis, Ta and low grade T1 tumours). All such cases are to be discussed with study chairs and rationale for decision documented.
  22. Concurrent illness, including severe infection that might jeopardise the ability of the participant to undergo the procedures outlined in this protocol with reasonable safety (HIV infection is not an exclusion criterion if it is controlled with anti-retroviral drugs that are unaffected by concomitant darolutamide)
  23. 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
  24. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception
  25. Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases
  26. Major surgery within 21 days prior to randomisation

Information from the National Library of Medicine

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): NCT04136353


Contacts
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Contact: DASL Trial Coordinator 61295625000 dasl@ctc.usyd.edu.au

Sponsors and Collaborators
University of Sydney
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Bayer
Cancer Trials Ireland
Canadian Cancer Trials Group
Investigators
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Study Chair: Christopher Sweeney Dana-Farber Cancer Institute and Harvard Medical School
Study Chair: Tamim Niazi Jewish General Hospital and McGill University

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Responsible Party: University of Sydney
ClinicalTrials.gov Identifier: NCT04136353     History of Changes
Other Study ID Numbers: ANZUP1801
U1111-1239-0771 ( Other Identifier: WHO Universal Trial Number )
First Posted: October 23, 2019    Key Record Dates
Last Update Posted: October 23, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Sydney:
clinically localised prostate cancer
very high risk
darolutamide
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Hormones
Prolactin Release-Inhibiting Factors
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs