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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04319783




Registration number
NCT04319783
Ethics application status
Date submitted
9/03/2020
Date registered
24/03/2020
Date last updated
7/04/2020

Titles & IDs
Public title
Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA
Scientific title
Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA
Secondary ID [1] 0 0
U1111-1242-9233
Secondary ID [2] 0 0
TROG 19.06
Universal Trial Number (UTN)
Trial acronym
DECREASE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Prostate Carcinoma 0 0
Cancer of Prostate 0 0
PSA 0 0
Castrate Resistant 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: Other - Radiotherapy

Experimental: Darolutamide - Darolutimide 600mg BD

Experimental: Local consolidation Radiotherapy + Darolutamide - Darolutimide 600mg BD + local consolidative radiotherapy, with a biological equivalent dose of 30Gy/10fx or greater if delivered with SABR. SABR is the preferred treatment approach, however conventional radiotherapy is acceptable. To up to 5 sites of disease


Treatment: Drugs: Darolutamide
Darolutamide alone

Treatment: Other: Radiotherapy
Darolutamide + Consolidation Radiotherapy

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
Undetectable PSA at 12 months - Undetectable PSA at 12 months
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
Radiological progression free survival - Radiological progression free survival
Timepoint [1] 0 0
36 months
Secondary outcome [2] 0 0
Distribution of disease on baseline PSMA-PET/CT imaging - Distribution of bone, nodal, visceral and recurrent primary disease on PSMA-PET/CT
Timepoint [2] 0 0
36 months
Secondary outcome [3] 0 0
Biochemical progression free survival - Biochemical progression free survival
Timepoint [3] 0 0
36 months
Secondary outcome [4] 0 0
Treatment related adverse event - Treatment related adverse events (CTCAE v 5.0)
Timepoint [4] 0 0
36 months
Secondary outcome [5] 0 0
Overall survival - Overall survival
Timepoint [5] 0 0
36 months
Secondary outcome [6] 0 0
Patterns of disease on PSMA PET/CT after 12 weeks of commencing Darolutamide, and at time of disease progression - PSMA avid disease at irradiated site / unirradiated site / bone / local / nodal / visceral
Timepoint [6] 0 0
3 months

Eligibility
Key inclusion criteria
- Males aged 18 years or older.

- Has provided written Informed Consent for participation in this trial.

- Histological or cytologically confirmed adenocarcinoma of prostate without
neuroendocrine differentiation or small cell features.

- Castration-resistant prostate cancer (CRPC) defined as at least 2 consecutive PSA
rises obtained at least 1 week apart in the setting of castrate testosterone levels
(see below). If the patient has a history of anti-androgen use and recent withdrawal,
the most recent PSA value must be obtained at least 4 weeks after anti-androgen
withdrawal.

- Castrate level of serum testosterone (<1.7 nmol/l [50 ng/dl]) on gonadotrophin -
releasing hormone (GnRH) agonist or antagonist therapy or after bilateral orchiectomy.
Patients who have not undergone bilateral orchiectomy must continue GnRH therapy
during the study.

- A baseline PSA level of at least 2ng per millilitre and a PSA doubling time of 10
months or less.

- An ECOG performance status score of 0 or 1.

- Blood counts at screening: haemoglobin =9.0 g/dl, absolute neutrophil count =1500/µl
(1.5×109/l), platelet count =100,000/µl (100×109/l) (patient must not have received
any growth factor or blood transfusion within 7 days of the haematology laboratory
obtained at screening).

- Screening values of serum alanine transaminase (ALT) and aspartate transaminase (AST)
=2.5 x upper limit of normal (ULN), total bilirubin =1.5 x ULN (except patients with a
diagnosis of Gilbert's disease), creatinine =2.0 x ULN.

- At least 1 site of PSMA-avid disease on PSMA-PET imaging in any of the following
regions:

- Local recurrence within the prostate gland or prostate bed

- Regional lymph node disease (below the aortic bifurcation)

- Extra-pelvic lymph node, bone or soft tissue metastatic disease
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with detectable metastases or a history of metastatic disease on conventional
imaging (whole body bone scan and computed tomography (CT) of the pelvis, abdomen and
chest). NOTE: Presence of pelvic lymph nodes <2 cm in short axis below the aortic
bifurcation is allowed.

- Prior treatment with: (1) second-generation androgen receptor (AR) antagonists such as
enzalutamide and apalutamide, or darolutamide or other investigational AR antagonists;
(2) CYP17 enzyme inhibitors, such as abiraterone acetate and orteronel; or (3) oral
ketoconazole.

- Use of estrogens or 5-a reductase inhibitors (finasteride, dutasteride) or
anti-androgens (bicalutamide, flutamide, nilutamide, cyproterone acetate) within 28
days before randomisation.

- Use of systemic corticosteroid with a dose greater than the equivalent 10 mg of
prednisone/day within 28 days before randomisation.

- Radiation therapy (external beam radiation therapy [EBRT], brachytherapy, or
radiopharmaceuticals) within 12 weeks prior to randomisation.

- Initiation of treatment with an osteoclast-targeted therapy (bisphosphonate or
denosumab) to prevent skeletal-related events within 12 weeks before randomisation.
NOTE: Patients receiving osteoclast-targeted therapy to prevent bone loss at a dose
and schedule indicated for osteoporosis may continue treatment at the same dose and
schedule, providing it was commenced at least 28 days before randomisation.

- Any of the following within 6 months before randomisation: stroke, myocardial
infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft;
congestive heart failure New York Heart Association (NYHA) Class III or IV.

- Uncontrolled hypertension as indicated by a systolic blood pressure =160 mmHg or
diastolic blood pressure =100 mmHg at screening.

- Prior malignancy. NOTE: Adequately treated basal cell or squamous cell carcinoma of
skin or superficial bladder cancer that has not spread behind the connective tissue
layer (i.e., pTis, pTa, and pT1) is allowed, as well as any other cancer for which the
last anti-cancer therapeutic intervention has been completed - 5 years ago and from
which the patient has been disease-free.

- Gastrointestinal disorder or procedure that expects to interfere significantly with
the absorption of study treatment.

- Unable to swallow study medications and comply with study requirements.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet 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)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
3002 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Trans-Tasman Radiation Oncology Group (TROG)
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Bayer
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Peter MacCallum Cancer Centre, Australia
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Darolutamide is a drug that has a proven survival benefit in non-metastatic (M0) castrate
resistant prostate cancer when using conventional imaging. However, it is estimated that >90%
of patients have disease apparent when using PSMA PET. This study investigates the use of
local consolidation radiotherapy in this cohort of men.
Trial website
https://clinicaltrials.gov/show/NCT04319783
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Shankar Siva
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Rebecca Montgomery
Address 0 0
Country 0 0
Phone 0 0
+61 2 4014 3910
Fax 0 0
Email 0 0
decrease@trog.com.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04319783