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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05938270




Registration number
NCT05938270
Ethics application status
Date submitted
16/05/2023
Date registered
10/07/2023

Titles & IDs
Public title
A Study to Investigate the Biological Effects of Saruparib (AZD5305), Darolutamide, and in Combination in Men With Newly Diagnosed Prostate Cancer.
Scientific title
An Open-label, Randomised, Phase-I, Multi-Centre Study to Investigate the Biological Effects of Saruparib (AZD5305) Alone, Darolutamide Alone, and in Combination Given Prior to Radical Prostatectomy in Men With Newly Diagnosed Prostate Cancer (ASCERTAIN)
Secondary ID [1] 0 0
D9721C00002
Universal Trial Number (UTN)
Trial acronym
ASCERTAIN
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 - Saruparib (AZD5305)
Treatment: Drugs - Darolutamide
Other interventions - No Treatment

Other: Saruparib (AZD5305) only - Participant will receive Saruparib (AZD5305) once daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days)

Other: Saruparib (AZD5305) + Darolutamide - Participant will receive Saruparib (AZD5305) once daily + darolutamide twice daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days).

Other: No Treatment - No study treatment is to be taken by the participants in this arm. Radical prostatectomy should be performed as per local practice

Other: Darolutamide Only - Participant will receive darolutamide twice daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days).


Treatment: Drugs: Saruparib (AZD5305)
Saruparib (AZD5305) given orally once daily

Treatment: Drugs: Darolutamide
Darolutamide tablet is 300mg, given BD orally, twice daily- total dose 1200mg

Other interventions: No Treatment
No study treatment is to be taken by the participants in this arm. Radical prostatectomy should be performed as per local practice
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Fold change in % ?H2AX positive cells from baseline value in tumour samples
Timepoint [1] 0 0
Tumour biopsy taken at diagnosis within approx 2 months of Day 1 planned start of study treatment; post treatment tumour biopsy taken following 21 days (+ up to 7 days) of study treatment
Secondary outcome [1] 0 0
Severity of Treatment-Emergent AEs/SAEs per CTCAE v5.0
Timepoint [1] 0 0
Day 1 to 28 days post-surgery
Secondary outcome [2] 0 0
Incidence of Treatment-Emergent AEs/SAEs per CTCAE v5.0
Timepoint [2] 0 0
Day 1 to 28 days post-surgery
Secondary outcome [3] 0 0
Number of patients with abnormal laboratory values
Timepoint [3] 0 0
Day 1 to 28 days post-surgery
Secondary outcome [4] 0 0
Change from baseline in blood pressure reported as clinically significant
Timepoint [4] 0 0
Day 1 to 28 days post-surgery
Secondary outcome [5] 0 0
Change from baseline in heart rate reported as clinically significant
Timepoint [5] 0 0
Day 1 to 28 days post-surgery
Secondary outcome [6] 0 0
Change from baseline in QTc value
Timepoint [6] 0 0
Day 1 to 28 days post-surgery
Secondary outcome [7] 0 0
Number of participants undergoing planned surgery
Timepoint [7] 0 0
Measured based on Day 1 to Day 21 of treatment
Secondary outcome [8] 0 0
Reasons of participants requiring treatment-related and non-treatment related delays of surgery and delays > 7 days from scheduled day
Timepoint [8] 0 0
Measured based on Day 1 to Day 21 of treatment
Secondary outcome [9] 0 0
Number of participants requiring treatment-related and non-treatment related delays of surgery and delays > 7 days from scheduled day
Timepoint [9] 0 0
Measured based on Day 1 to Day 21 of treatment
Secondary outcome [10] 0 0
Change in Ki-67 % positive cells from baseline in tumour samples
Timepoint [10] 0 0
Measured based on Day 1 to Day 21 of treatment

Eligibility
Key inclusion criteria
* male participants >/= 18 years old
* participants deemed suitable for radical prostatectomy
* participants with localised prostate cancer with unfavourable intermediate/high/very high risk eligible for prostatectomy
* adequate organ and marrow function as per protocol
* capable of giving signed informed consent
* provision of signed and dated written Optional Genetic Research Information
* Available FFPE diagnostic tumour biopsy samples
* Participants must use a condom (with spermicide) from screening to 6 months after screening and refrain from fathering a child or donating sperm
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including, active bleeding diatheses, or active infection including HepB, hepatitis C and HIV. Screening for chronic conditions is not required.

1. Active HBV is defined by a known positive HBsAg result. Participants with a past or resolved HBV infection (defined as the presence of HepB antibody and absence of HBsAg) are eligible.
2. Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
* Participants with any known predisposition to bleeding (eg, active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy).
* Participants with history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). Specific screening for MDS/AML not required.
* Prior malignancy within 3 years of screening whose natural history, in the Investigator's opinion, has the potential to interfere with safety and efficacy assessments of the investigational regimen.
* Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of TdP.
* Any of the following cardiac criteria:

1. Mean resting corrected QT interval (QTcF) > 450 milliseconds or QTcF < 340 milliseconds obtained from triplicate ECGs and averaged, recorded within 5 minutes.
2. Any factors that increase the risk of QT prolongation, shortening or risk of arrhythmic events such as hypokalaemia, congenital long or short QT syndrome, family history of long QT syndrome, familial short QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong or shorten the QT interval.
3. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, second or third degree atrioventricular block and clinically significant sinus node dysfunction not treated with pacemaker.
* Other CVS diseases as defined by any of the following:

1. Symptomatic heart failure (as defined by NYHA class = 2).
2. uncontrolled hypertension.
3. hypertensive heart disease with significant left ventricular hypertrophy.
4. History of acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention or coronary artery bypass grafting within 6 months prior to screening.
5. cardiomyopathy of any aetiology.
6. presence of clinically significant valvular heart disease.
7. history of atrial or ventricular arrhythmia requiring acute treatment; participants with atrial fibrillation and optimally controlled ventricular rate (heart rate < 100 bpm) are permitted.
8. transient ischaemic attack, or stroke within 6 months prior to screening.
9. participants with symptomatic hypotension at screening.
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of Saruparib (AZD5305).
* History of prior malignancy, treated with chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, or other anticancer agent within 3 years of screening. Previously localised surgically treated malignancy is acceptable, if no evidence of recurrence.
* Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
* Prior treatment with any systemic or localised anti-cancer treatment for the localised prostate cancer.
* During the 4 weeks prior to the first dose, receiving immune modulatory agents including but not limited to, continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent.
* Concomitant use of medications or herbal supplements known to be:

1. Strong CYP3A4 inducers/inhibitors (applies for Saruparib (AZD5305) and Saruparib (AZD5305) + darolutamide arms)
2. Strong or moderate CYP3A4 and P-glycoprotein inducers (applies to darolutamide arm and Saruparib (AZD5305) + darolutamide arm) This is including, but not limited to, the prohibited medications listed in CSP Appendix G, or inability to stop the use thereof, at least 21 days or at least 5 half-lives (whichever is longer) before the first dose of study treatment until 30 days after the last dose of study treatment.
* Treatment with any investigational agents or study interventions from a previous clinical study within 5 half-lives or 3 weeks (whichever is longer) of the first dose of study treatment.
* Participants with contraindication to darolutamide for treatment arms
* Unable to comply with the visits and assessments.
* In the opinion of the Investigators should not be included in this study.

No treatment arm only: if any participant meets exclusion 4, 9 or 11, they are not to be included in the study.

Study design
Purpose of the study
Other
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 1
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
21/09/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
25/02/2025
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Melbourne
Recruitment hospital [2] 0 0
Research Site - South Brisbane
Recruitment postcode(s) [1] 0 0
VIC 3000 - Melbourne
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Michigan
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
United States of America
State/province [3] 0 0
Rhode Island
Country [4] 0 0
Canada
State/province [4] 0 0
British Columbia
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
Netherlands
State/province [7] 0 0
Amsterdam
Country [8] 0 0
Netherlands
State/province [8] 0 0
Nijmegen
Country [9] 0 0
Spain
State/province [9] 0 0
Barcelona
Country [10] 0 0
Spain
State/province [10] 0 0
Madrid
Country [11] 0 0
Spain
State/province [11] 0 0
Valencia
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Cambridge
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Manchester
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal

Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05938270