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

Sponsor
University of Sydney (Other)
Overall Status
Recruiting
CT.gov ID
NCT04136353
Collaborator
Australian and New Zealand Urogenital and Prostate Cancer Trials Group (Other), Bayer (Industry), Cancer Trials Ireland (Other), Canadian Cancer Trials Group (Other), Memorial Sloan Kettering Cancer Center (Other), Prostate Cancer Clinical Trials Consortium (Other)
1,100
Enrollment
54
Locations
2
Arms
100
Anticipated Duration (Months)
20.4
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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 DiseaseIntervention/TreatmentPhase
  • Drug: Darolutamide
  • Drug: Placebo oral tablet
  • Drug: Luteinizing Hormone-Releasing Hormone Analog
  • Radiation: External Beam Radiotherapy
Phase 3

Study Design

Study Type:
Interventional
Anticipated 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
Actual Study Start Date :
Mar 31, 2020
Anticipated Primary Completion Date :
Jan 31, 2028
Anticipated Study Completion Date :
Jul 31, 2028

Arms and Interventions

ArmIntervention/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.

Outcome Measures

Primary Outcome Measures

  1. Metastasis-free survival [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 [Through study completion, an average of 5 years]

  2. Prostate cancer-specific survival [Through study completion, an average of 5 years]

  3. PSA-progression free survival [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 [Through study completion, an average of 5 years]

  5. Time to castration-resistance [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, RTOG/EORTC acute/late radiation morbidity criteria) [Approximately 12-weekly for 2 years from randomisation until 30 days after the last dose of study treatment.]

  7. Health-related quality of life [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 [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 [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
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 aorta into 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 PSA* ≥ 0.1 ng/mL that has risen or remained stable (within ≤ 0.05 ng/mL) since a previous level at least 1 week earlier, 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 aorta into 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) * This PSA level must be measured within 60 days prior to randomisation. However, if a participant has already commenced endocrine therapy (ET) for prostate cancer, this PSA level must be measured within 180 days prior to commencing ET.

  1. Adequate bone marrow function: Haemoglobin ≥ 100g/L, white cell count (WCC) ≥ 4.0x109/L, absolute neutrophil count (ANC) ≥ 1.5x109/L and platelets > 100 x 109/L

  2. 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)

  3. Adequate renal function: calculated creatinine clearance > 30 mL/min (Cockroft-Gault)

  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1

  5. Study treatment both planned and able to start within 7 days after randomisation

  6. Willing to complete health-related quality of life (HRQL) questionnaires UNLESS is unable to complete because of literacy or limited vision

  7. Willing and able to comply with all study requirements, including standard of care treatment such as EBRT, timing and/or nature of required assessments

  8. Signed, written informed consent

Exclusion Criteria:
  1. Prostate cancer with predominant non-adenocarcinoma features (sarcomatoid or spindle cell or neuroendocrine small cell or squamous cell components or other non-adenocarcinoma)

  2. 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).

  3. Evidence of metastatic disease. Minimum imaging requirements to exclude metastatic disease are diagnostic quality imaging of both the pelvis and the abdomen (CT or MRI), chest (CXR or CT), and a whole body radioisotope bone scan (WBBS).

  • If endocrine therapy (ET) had not started, imaging must be within 60 days prior to randomisation.

  • If ET has been started, imaging must have been performed no more than 60 days prior to starting ET and no more than 30 days after starting ET and prior to randomisation.

  1. PSA > 100 ng/mL at any time

  2. Any prior use of new generation potent AR inhibition (abiraterone, enzalutamide, apalutamide, darolutamide or similar agents).

  3. Prior endocrine therapy for prostate cancer except for the following which are allowed:

  • (i) LHRHA and/or (ii) a first-generation nonsteroidal antiandrogen (NSAA) are allowed if commenced no more than 90 days before randomisation. If an NSAA has been used, it must be stopped before starting study treatment with darolutamide/placebo; and

  • Prior use of 5-alpha reductase inhibitor is allowed and if used it must be stopped before starting study treatment with darolutamide/placebo

  1. Bilateral orchidectomy

  2. Prior pelvic brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields that would preclude the required RT

  3. History of

  • Loss of consciousness or transient ischemic attack or stroke within 6 months prior to randomisation, or

  • Significant cardiovascular disease within 6 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), coronary artery bypass graft. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.

  1. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of darolutamide, including difficulty swallowing tablets

  2. 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 with a history of malignancy within the last 5 years are to be discussed with study team before randomisation. Melanoma in-situ and other adequately treated in-situ neoplasms are not considered malignancies for the purposes of eligibility assessment.

  3. 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)

  4. 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

  5. Patients who are sexually active with women of child-bearing potential and not willing/able to use medically acceptable and highly effective forms of contraception during study treatment and for at least 4 weeks after completion of study treatment.

Contraception must include:
  • Condom use (also required if sexual partner is pregnant), and

  • Additional birth control with low failure rate (less than 1% per year) when used consistently and correctly. E.g. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, true sexual abstinence.

True sexual abstinence will only be an acceptable form of contraception when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study treatment, and withdrawal are not acceptable methods of contraception.

  1. Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases

  2. Major surgery within 21 days prior to randomisation

  3. Patients with history of hypersensitivity to the study treatment

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Memorial Sloan Kettering Basking RidgeBasking RidgeNew JerseyUnited States07920
2Memorial Sloan Kettering MonmouthMiddletownNew JerseyUnited States07748
3Memorial Sloan Kettering BergenMontvaleNew JerseyUnited States07645
4New Mexico Oncology & Hematology ConsultantsAlbuquerqueNew MexicoUnited States87109
5Memorial Sloan Kettering CommackCommackNew YorkUnited States11725
6Memorial Sloan Kettering WestchesterHarrisonNew YorkUnited States10604
7Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10065
8Memorial Sloan Kettering NassauUniondaleNew YorkUnited States11553
9Dayton Physicians NetworkKetteringOhioUnited States45409
10Border Medical Oncology Research UnitAlburyNew South WalesAustralia2640
11Gosford HospitalGosfordNew South WalesAustralia2250
12GenesisCare NewcastleNewcastleNew South WalesAustralia2290
13Calvary Mater NewcastleNewcastleNew South WalesAustralia2298
14St Vincent's Public HospitalSydneyNew South WalesAustralia2010
15Prince of Wales HospitalSydneyNew South WalesAustralia2031
16Chris O'Brien LifehouseSydneyNew South WalesAustralia2050
17Northern Cancer InstituteSydneyNew South WalesAustralia2065
18Sydney Adventist HospitalSydneyNew South WalesAustralia2076
19Liverpool HospitalSydneyNew South WalesAustralia2170
20St George HospitalSydneyNew South WalesAustralia2217
21Campbelltown hospitalSydneyNew South WalesAustralia2560
22Wollongong HospitalWollongongNew South WalesAustralia2500
23ROPARTBrisbaneQueenslandAustralia4101
24Royal Brisbane and Women's HospitalHerstonQueenslandAustralia4029
25Icon Cancer CentreSouthportQueenslandAustralia4215
26Townsville HospitalTownsvilleQueenslandAustralia4814
27Princess Alexandra HospitalWoolloongabbaQueenslandAustralia4102
28Ashford Cancer Centre ResearchKurralta ParkSouth AustraliaAustralia5037
29Royal Hobart HospitalHobartTasmaniaAustralia7000
30Peter MacCallum Cancer Centre - Bendigo CampusBendigoVictoriaAustralia3550
31Peter MacCallum Cancer Centre (Moorabbin Campus)Bentleigh EastVictoriaAustralia3165
32Box Hill HospitalBox HillVictoriaAustralia3128
33GenesisCare Cabrini (Gandel Wing), Cabrini Hospital MalvernMalvernVictoriaAustralia3144
34Peter MacCallum Cancer CentreMelbourneVictoriaAustralia3000
35The Alfred HospitalMelbourneVictoriaAustralia3004
36Sunshine HospitalSt AlbansVictoriaAustralia3021
37Fiona Stanley HospitalMurdochWestern AustraliaAustralia6143
38Sir Charles Gairdner HospitalNedlandsWestern AustraliaAustralia6006
39Western Manitoba Cancer Centre - Prairie Mountain HealthBrandonManitobaCanadaR7A 2B3
40Kingston Health Sciences CentreKingstonOntarioCanadaK7L 2V7
41Queen Elizabeth II Health Sciences CentreLondonOntarioCanadaB3H 1V7
42Sault Area Hospital - Algoma District Cancer ProgramSault Ste MarieOntarioCanadaP6B 0A8
43Ottawa Hospital Research InstituteTorontoOntarioCanadaK1H 8L6
44Odette Cancer Centre - Sunnybrook HospitalTorontoOntarioCanadaM4N 3M5
45Princess Margaret Cancer CentreTorontoOntarioCanadaM5G 2M9
46Jewish General HospitalMontréalQuebecCanadaH3T 1E2
47Centre Hospitalier Universitaire de SherbrookeSherbrookeQuebecCanadaJ1H 5N4
48Cork University HospitalCorkIrelandT12 EC8P
49Bon Secours Hospital Cork in association with UPMC Hillman CentreCorkIrelandT23
50Mater Misericordiae University HospitalDublinIrelandD07 A8NN
51Mater Private DublinDublinIrelandD07 WKW8
52Auckland City HospitalAucklandNew Zealand1023
53Christchurch HospitalChristchurchNew Zealand8011
54Palmerston North HospitalPalmerston NorthNew Zealand4442

Sponsors and Collaborators

  • University of Sydney
  • Australian and New Zealand Urogenital and Prostate Cancer Trials Group
  • Bayer
  • Cancer Trials Ireland
  • Canadian Cancer Trials Group
  • Memorial Sloan Kettering Cancer Center
  • Prostate Cancer Clinical Trials Consortium

Investigators

  • Study Chair: Christopher Sweeney, Dana-Farber Cancer Institute and Harvard Medical School
  • Study Chair: Tamim Niazi, Jewish General Hospital and McGill University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
University of Sydney
ClinicalTrials.gov Identifier:
NCT04136353
Other Study ID Numbers:
  • ANZUP1801
  • U1111-1239-0771
First Posted:
Oct 23, 2019
Last Update Posted:
Oct 8, 2021
Last Verified:
Oct 1, 2021
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by University of Sydney
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 8, 2021