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

NCT05938270 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: D9721C000022023-503691-25-00
• Study Type: interventional
• Target: 120
• Locations: 7 countries
• Sites: 19

Brief Summary

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).

Conditions

Prostate Cancer

Keywords

Prostate cancer, radical prostatectomy, Darolutamide, Saruparib (AZD5305)

Outcome Measures

Primary Outcomes (1)

• Fold change in % γH2AX positive cells from baseline value in tumour samples

  To assess the effects of study treatment on γH2AX change in participants with localised prostate cancer

  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 Outcomes (10)

• Severity of Treatment-Emergent AEs/SAEs per CTCAE v5.0

  Day 1 to 28 days post-surgery

• Incidence of Treatment-Emergent AEs/SAEs per CTCAE v5.0

  Day 1 to 28 days post-surgery

• Number of patients with abnormal laboratory values

  Day 1 to 28 days post-surgery

• Change from baseline in blood pressure reported as clinically significant

  Day 1 to 28 days post-surgery

• Change from baseline in heart rate reported as clinically significant

  Day 1 to 28 days post-surgery

Study Arms (4)

Saruparib (AZD5305) only

OTHER

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)

Drug: Saruparib (AZD5305)

Saruparib (AZD5305) + Darolutamide

OTHER

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).

Drug: Saruparib (AZD5305); Drug: Darolutamide

No Treatment

OTHER

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

Other: No Treatment

Darolutamide Only

OTHER

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).

Drug: Darolutamide

Interventions

Saruparib (AZD5305) DRUG

Saruparib (AZD5305) given orally once daily

Also known as: Darolutamide is also known as Nubeqa

Saruparib (AZD5305) + Darolutamide; Saruparib (AZD5305) only

Darolutamide DRUG

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

Also known as: Darolutamide is also known as Nubeqa

Darolutamide Only; Saruparib (AZD5305) + Darolutamide

No Treatment OTHER

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

No Treatment

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male participants \>/=18 years of age
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.
• 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:
• Mean resting corrected QT interval (QTcF) \> 450 milliseconds or QTcF \< 340 milliseconds obtained from triplicate ECGs and averaged, recorded within 5 minutes.
• 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.
• 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:
• Symptomatic heart failure (as defined by NYHA class ≥ 2).
• uncontrolled hypertension.
• hypertensive heart disease with significant left ventricular hypertrophy.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (19)

Research Site

Detroit, Michigan, 48202, United States

RECRUITING

Research Site

Providence, Rhode Island, 02903, United States

RECRUITING

Research Site

Melbourne, VIC 3000, Australia

RECRUITING

Research Site

South Brisbane, 4101, Australia

RECRUITING

Research Site

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

Research Site

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Research Site

Québec, Quebec, G1J 1Z4, Canada

RECRUITING

Research Site

Amsterdam, 1066CX, Netherlands

RECRUITING

Research Site

Nijmegen, 6525 GA, Netherlands

RECRUITING

Research Site

Barcelona, 08036, Spain

RECRUITING

Research Site

Barcelona, 8035, Spain

RECRUITING

Research Site

Madrid, 28041, Spain

RECRUITING

Research Site

Valencia, 46009, Spain

RECRUITING

Research Site

Ankara, 06100, Turkey (Türkiye)

WITHDRAWN

Research Site

Ankara, 6200, Turkey (Türkiye)

WITHDRAWN

Research Site

Istanbul, 34010, Turkey (Türkiye)

WITHDRAWN

Research Site

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Research Site

Manchester, M20 4BX, United Kingdom

RECRUITING

Research Site

Newcastle upon Tyne, NE7 7AF, United Kingdom

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

AZD5305; darolutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomised, phase 1 multicentre study

Study Record Dates

• First Submitted: May 16, 2023
• First Posted: July 10, 2023
• Study Start: September 21, 2023
• Primary Completion (Estimated): August 17, 2026
• Study Completion (Estimated): August 17, 2026
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: 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.
• Access Criteria: 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.

Locations

CA (3); TU (3); NL (2); GB (3); US (2); AU (2); ES (4)