Trial Title:
A Study to Investigate the Biological Effects of Saruparib (AZD5305), Darolutamide, and in Combination in Men With Newly Diagnosed Prostate Cancer.
NCT ID:
NCT05938270
Condition:
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Conditions: Keywords:
Prostate cancer, radical prostatectomy, Darolutamide, Saruparib (AZD5305)
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Randomised, phase 1 multicentre study
Primary purpose:
Basic Science
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Saruparib (AZD5305)
Description:
Saruparib (AZD5305) given orally once daily
Arm group label:
Saruparib (AZD5305) + Darolutamide
Arm group label:
Saruparib (AZD5305) only
Other name:
Darolutamide is also known as Nubeqa
Intervention type:
Drug
Intervention name:
Darolutamide
Description:
Darolutamide tablet is 300mg, given BD orally, twice daily- total dose 1200mg
Arm group label:
Darolutamide Only
Arm group label:
Saruparib (AZD5305) + Darolutamide
Other name:
Darolutamide is also known as Nubeqa
Intervention type:
Other
Intervention name:
No Treatment
Description:
No study treatment is to be taken by the participants in this arm. Radical prostatectomy
should be performed as per local practice
Arm group label:
No Treatment
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).
Detailed description:
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).
Criteria for eligibility:
Criteria:
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.
Gender:
Male
Gender based:
Yes
Gender description:
Male participants >/=18 years of age
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Research Site
Address:
City:
Detroit
Zip:
48202
Country:
United States
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Withdrawn
Facility:
Name:
Research Site
Address:
City:
Providence
Zip:
02903
Country:
United States
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Melbourne
Zip:
VIC 3000
Country:
Australia
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
South Brisbane
Zip:
4101
Country:
Australia
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Vancouver
Zip:
V5Z 1M9
Country:
Canada
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Québec
Zip:
G1J 4Z1
Country:
Canada
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Amsterdam
Zip:
1066CX
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Nijmegen
Zip:
6525 GA
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Barcelona
Zip:
8035
Country:
Spain
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Valencia
Zip:
46009
Country:
Spain
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Cambridge
Zip:
CB2 0QQ
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Newcastle upon Tyne
Zip:
NE7 7AF
Country:
United Kingdom
Status:
Recruiting
Start date:
September 21, 2023
Completion date:
November 14, 2025
Lead sponsor:
Agency:
AstraZeneca
Agency class:
Industry
Source:
AstraZeneca
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05938270
