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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04136353




Registration number
NCT04136353
Ethics application status
Date submitted
17/10/2019
Date registered
23/10/2019
Date last updated
18/10/2021

Titles & IDs
Public title
Darolutamide Augments Standard Therapy for Localised Very High-Risk Cancer of the Prostate
Scientific 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
Secondary ID [1] 0 0
U1111-1239-0771
Secondary ID [2] 0 0
ANZUP1801
Universal Trial Number (UTN)
Trial acronym
DASL-HiCaP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Darolutamide
Treatment: Drugs - Placebo oral tablet
Treatment: Drugs - Luteinizing Hormone-Releasing Hormone Analog
Treatment: Other - External Beam Radiotherapy

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.

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.


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

Treatment: Drugs: Placebo oral tablet
2 oral tablets twice daily for 96 weeks

Treatment: Drugs: 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.

Treatment: Other: 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.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Metastasis-free survival - 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.
Timepoint [1] 0 0
Through study completion, an average of 5 years
Secondary outcome [1] 0 0
Overall survival
Timepoint [1] 0 0
Through study completion, an average of 5 years
Secondary outcome [2] 0 0
Prostate cancer-specific survival
Timepoint [2] 0 0
Through study completion, an average of 5 years
Secondary outcome [3] 0 0
PSA-progression free survival - 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).
Timepoint [3] 0 0
Through study completion, an average of 5 years
Secondary outcome [4] 0 0
Time to subsequent hormonal therapy
Timepoint [4] 0 0
Through study completion, an average of 5 years
Secondary outcome [5] 0 0
Time to castration-resistance - Defined according to the PCWG3 criteria. If a participant has radiographic progression without serological progression, this will also be deemed castration resistant prostate cancer
Timepoint [5] 0 0
Through study completion, an average of 5 years
Secondary outcome [6] 0 0
Frequency and severity of adverse events (CTCAE v5.0, RTOG/EORTC acute/late radiation morbidity criteria)
Timepoint [6] 0 0
Approximately 12-weekly for 2 years from randomisation until 30 days after the last dose of study treatment.
Secondary outcome [7] 0 0
Health-related quality of life - 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)
Timepoint [7] 0 0
Through study completion, an average of 5 years
Secondary outcome [8] 0 0
Health-related quality of life - 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)
Timepoint [8] 0 0
Through study completion, an average of 5 years
Secondary outcome [9] 0 0
Health-related quality of life - 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.
Timepoint [9] 0 0
Through study completion, an average of 5 years
Secondary outcome [10] 0 0
Fear of cancer recurrence - 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.
Timepoint [10] 0 0
Through study completion, an average of 5 years

Eligibility
Key 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.

3. 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

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
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key 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. 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.

14. PSA > 100 ng/mL at any time

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

16. 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

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 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.

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 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.

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 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.

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

27. Patients with history of hypersensitivity to the study treatment

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Border Medical Oncology Research Unit - Albury
Recruitment hospital [2] 0 0
Gosford Hospital - Gosford
Recruitment hospital [3] 0 0
GenesisCare Newcastle - Newcastle
Recruitment hospital [4] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [5] 0 0
St Vincent's Public Hospital - Sydney
Recruitment hospital [6] 0 0
Prince of Wales Hospital - Sydney
Recruitment hospital [7] 0 0
Chris O'Brien Lifehouse - Sydney
Recruitment hospital [8] 0 0
Northern Cancer Institute - Sydney
Recruitment hospital [9] 0 0
Sydney Adventist Hospital - Sydney
Recruitment hospital [10] 0 0
Liverpool Hospital - Sydney
Recruitment hospital [11] 0 0
St George Hospital - Sydney
Recruitment hospital [12] 0 0
Campbelltown hospital - Sydney
Recruitment hospital [13] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [14] 0 0
ROPART - Brisbane
Recruitment hospital [15] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [16] 0 0
Icon Cancer Centre - Southport
Recruitment hospital [17] 0 0
Townsville Hospital - Townsville
Recruitment hospital [18] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [19] 0 0
Ashford Cancer Centre Research - Kurralta Park
Recruitment hospital [20] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [21] 0 0
Peter MacCallum Cancer Centre - Bendigo Campus - Bendigo
Recruitment hospital [22] 0 0
Peter MacCallum Cancer Centre (Moorabbin Campus) - Bentleigh East
Recruitment hospital [23] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [24] 0 0
GenesisCare Cabrini (Gandel Wing), Cabrini Hospital Malvern - Malvern
Recruitment hospital [25] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [26] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [27] 0 0
Sunshine Hospital - St Albans
Recruitment hospital [28] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [29] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2250 - Gosford
Recruitment postcode(s) [3] 0 0
2290 - Newcastle
Recruitment postcode(s) [4] 0 0
2298 - Newcastle
Recruitment postcode(s) [5] 0 0
2010 - Sydney
Recruitment postcode(s) [6] 0 0
2031 - Sydney
Recruitment postcode(s) [7] 0 0
2050 - Sydney
Recruitment postcode(s) [8] 0 0
2065 - Sydney
Recruitment postcode(s) [9] 0 0
2076 - Sydney
Recruitment postcode(s) [10] 0 0
2170 - Sydney
Recruitment postcode(s) [11] 0 0
2217 - Sydney
Recruitment postcode(s) [12] 0 0
2560 - Sydney
Recruitment postcode(s) [13] 0 0
2500 - Wollongong
Recruitment postcode(s) [14] 0 0
4101 - Brisbane
Recruitment postcode(s) [15] 0 0
4029 - Herston
Recruitment postcode(s) [16] 0 0
4215 - Southport
Recruitment postcode(s) [17] 0 0
4814 - Townsville
Recruitment postcode(s) [18] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [19] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [20] 0 0
7000 - Hobart
Recruitment postcode(s) [21] 0 0
3550 - Bendigo
Recruitment postcode(s) [22] 0 0
3165 - Bentleigh East
Recruitment postcode(s) [23] 0 0
3128 - Box Hill
Recruitment postcode(s) [24] 0 0
3144 - Malvern
Recruitment postcode(s) [25] 0 0
3000 - Melbourne
Recruitment postcode(s) [26] 0 0
3004 - Melbourne
Recruitment postcode(s) [27] 0 0
3021 - St Albans
Recruitment postcode(s) [28] 0 0
6143 - Murdoch
Recruitment postcode(s) [29] 0 0
6006 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
United States of America
State/province [2] 0 0
New Mexico
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
Canada
State/province [5] 0 0
Manitoba
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
Canada
State/province [8] 0 0
Québec
Country [9] 0 0
Ireland
State/province [9] 0 0
Cork
Country [10] 0 0
Ireland
State/province [10] 0 0
Dublin
Country [11] 0 0
New Zealand
State/province [11] 0 0
Auckland
Country [12] 0 0
New Zealand
State/province [12] 0 0
Christchurch
Country [13] 0 0
New Zealand
State/province [13] 0 0
Palmerston North

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australian and New Zealand Urogenital and Prostate Cancer Trials Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Bayer
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Cancer Trials Ireland
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Canadian Cancer Trials Group
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Memorial Sloan Kettering Cancer Center
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Prostate Cancer Clinical Trials Consortium
Address [6] 0 0
Country [6] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04136353
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Christopher Sweeney
Address 0 0
Dana-Farber Cancer Institute and Harvard Medical School
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
DASL Trial Coordinator
Address 0 0
Country 0 0
Phone 0 0
+61 295 625 000
Fax 0 0
Email 0 0
dasl.study@sydney.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04136353