A Study to Investigate the Biological Effects of Saruparib (AZD5305), Darolutamide, and in Combination in Men With Newly Diagnosed Prostate Cancer.

NCT ID: NCT05938270

Last Updated: 2026-01-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-21

Study Completion Date

2026-08-17

Brief Summary

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A 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).

Detailed Description

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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).

Conditions

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Prostate Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomised, phase 1 multicentre study
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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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)

Group Type OTHER

Saruparib (AZD5305)

Intervention Type DRUG

Saruparib (AZD5305) given orally once daily

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).

Group Type OTHER

Saruparib (AZD5305)

Intervention Type DRUG

Saruparib (AZD5305) given orally once daily

Darolutamide

Intervention Type DRUG

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

No Treatment

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

Group Type OTHER

No Treatment

Intervention Type OTHER

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

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).

Group Type OTHER

Darolutamide

Intervention Type DRUG

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

Interventions

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Saruparib (AZD5305)

Saruparib (AZD5305) given orally once daily

Intervention Type DRUG

Darolutamide

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

Intervention Type DRUG

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 Type OTHER

Other Intervention Names

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Darolutamide is also known as Nubeqa Darolutamide is also known as Nubeqa

Eligibility Criteria

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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
* For participants participating in the Optional Genetic Research Only: 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

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). In case there is no Clinical MDS/AML suspicion, no specific screening for MDS/AML (by bone marrow/bone biopsy) is 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.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Detroit, Michigan, United States

Site Status RECRUITING

Research Site

Providence, Rhode Island, United States

Site Status RECRUITING

Research Site

Melbourne, , Australia

Site Status RECRUITING

Research Site

South Brisbane, , Australia

Site Status RECRUITING

Research Site

Vancouver, British Columbia, Canada

Site Status RECRUITING

Research Site

Toronto, Ontario, Canada

Site Status RECRUITING

Research Site

Québec, Quebec, Canada

Site Status RECRUITING

Research Site

Amsterdam, , Netherlands

Site Status RECRUITING

Research Site

Nijmegen, , Netherlands

Site Status RECRUITING

Research Site

Barcelona, , Spain

Site Status RECRUITING

Research Site

Barcelona, , Spain

Site Status RECRUITING

Research Site

Madrid, , Spain

Site Status RECRUITING

Research Site

Valencia, , Spain

Site Status RECRUITING

Research Site

Ankara, , Turkey (Türkiye)

Site Status WITHDRAWN

Research Site

Ankara, , Turkey (Türkiye)

Site Status WITHDRAWN

Research Site

Istanbul, , Turkey (Türkiye)

Site Status WITHDRAWN

Research Site

Cambridge, , United Kingdom

Site Status RECRUITING

Research Site

Manchester, , United Kingdom

Site Status RECRUITING

Research Site

Newcastle upon Tyne, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Canada Netherlands Spain Turkey (Türkiye) United Kingdom

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

1-877-240-9479

Other Identifiers

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2023-503691-25-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

D9721C00002

Identifier Type: -

Identifier Source: org_study_id

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