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Metastatic Castration Resistant Prostate Cancer (mCRPC)Phase 1REPAIRNCT05425862

Pidnarulex and Talazoparib in Patients With Metastatic Castration Resistant Prostate Cancer

A Phase 1 study testing Pidnarulex and Talazoparib in people with Metastatic Castration Resistant Prostate Cancer (mCRPC), run by Peter MacCallum Cancer Centre, Australia at 5 sites in Australia.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is phase I, open label, multicentre, dose-escalation study where both doses of talazoparib and pidnarulex will be escalated to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the combination. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Pidnarulex and Talazoparib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
5 sitesAustralia
Study dates
21 Oct 2022to 1 Oct 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient must be ≥18 years of age and must have provided written informed consent.
  • Histologically confirmed adenocarcinoma of the prostate without neuroendocrine or small cell differentiation.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
  • Patients must have had at least one prior treatment line of taxane (docetaxel) chemotherapy either in the hormone sensitive or castrate resistant setting unless the patient is deemed medically unsuitable for chemotherapy. If a patient has had docetaxel chemotherapy twice, this will be considered one line.
  • Patients must have progressed on a second-generation androgen receptor (AR) targeted agent (e.g. enzalutamide, abiraterone and/or apalutamide). Determination of disease progression on second-generation AR targeted agent will be made by the local Investigator.
  • Patients must have progressive disease (PD) for study entry. This is defined by Prostate Cancer Working Group 3 (PCWG3) as any one of the following:
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  • PSA progression: minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement.
  • Soft tissue or visceral disease progression as per Response Evaluation Criteria in Solid Tumours (RECIST1.1) criteria
  • Bone progression: ≥ 2 new lesions on bone scan
  • The PSA value at screening should be ≥ 5ng/ml for all patients registered on the study.
  • At least 3 weeks since the completion of surgery or radiotherapy prior to commencing study treatment. Any clinically relevant sequelae from the surgery or radiotherapy must have improved to Grade 1 prior to Cycle 1 Day 1.
  • Prior surgical orchiectomy or chemical castration maintained on luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist). Patients without prior surgical castration must be currently taking and willing to continue LHRH analogue (agonist or antagonist) therapy throughout the duration of study treatment.
  • Serum testosterone levels ≤ 50ng/dL (≤ 1.75nmol/L) within 28 days prior to Cycle 1 Day 1.
  • Imaging evidence of metastatic disease documented with either bone scan or computerised tomography (CT) scan.
  • At least 3 weeks since completion of prostate cancer vaccine therapy, radiation therapy or systemic therapy prior to Cycle 1 Day 1.
  • Patients must have a life expectancy ≥ 24 weeks.
  • Male patients must use barrier contraception during treatment and for 3 months after the last dose of study drug when having sexual intercourse with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception.
  • Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled assessments.
  • Patients must have adequate bone marrow, hepatic and renal function documented within 7 days prior to Cycle 1 Day 1, defined as:
  • Haemoglobin ≥100 g/L independent of transfusions (no red blood cell (RBC) transfusion in last 8 weeks)
  • Absolute neutrophil count (ANC) ≥1.2 x109/L
  • Platelets ≥120 x109/L
  • Total bilirubin ≤1.5 x upper limit of normal (ULN) except for patients with known Gilbert's syndrome where this applies to the conjugated bilirubin level.
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x ULN if there is no evidence of liver metastasis or ≤5 x ULN in the presence of liver metastases.
  • Albumin ≥ 30 g/L
  • Adequate renal function: patients must have creatinine clearance (CrCl) estimated of ≥ 50 mL/min using the Cockcroft-Gault equation

Who cannot join

  • Extensive marrow disease defined by a "Super Scan" on bone scintigraphy or diffuse marrow infiltration on prostate specific membrane antigen (PSMA) positron emission tomography (PET).
  • Previous history or presence of brain metastases or leptomeningeal metastases. A scan to confirm the absence of brain metastases is not required if there is no clinical suspicion on history.
  • Surgery or radiotherapy within < 3 weeks prior to Cycle 1 Day 1 (except for palliative reasons). Patients must have recovered from effects of any major surgery.
  • Patients with symptomatic or impending cord compression unless adequately treated and clinically stable for ≥ 4 weeks.
  • Any prior exposure to platinums, poly (ADP-ribose) polymerase (PARP) inhibitors, mitoxantrone or cyclophosphamide.
  • Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial lung disease on High Resolution CT scan or psychiatric illness/social situations that are likely to impede participation and/or compliance in the study.
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  • Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAE] Grade 2) caused by previous cancer therapy, excluding alopecia.
  • Other malignancies within the previous 2-years that have a high risk of recurrence other than basal cell, squamous cell carcinomas of skin, melanoma in situ or other cancers that are unlikely to recur within 24 months.
  • Previous history of interstitial lung disease or non-infectious pneumonitis.
  • Patients with a history or clinical features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML).
  • Patients unable to swallow orally administered medications or with gastrointestinal disorders likely to interfere with the absorption of the study medication.
  • Resting Electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the Investigator (e.g., unstable angina, uncontrolled or symptomatic arrhythmia, congestive heart failure, corrected QT interval by Frederica [QTcF] prolongation >500ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
  • Known hypersensitivity to talazoparib or pidnarulex or any of the excipients of talazoparib or pidnarulex.
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) 1/2. Serology only required if there is clinical suspicion on history. HIV-infected (HIV1/2 antibody-positive) patients may participate if they meet all the following eligibility requirements:
  • They must be on an anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks They must have a CD4 count ≥250 cells/μL over the past 6 months on the same anti-retroviral regimen and must not have had a CD4 count <200 cells/μl over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy-induced bone marrow suppression
  • For patients who have received chemotherapy in the past 6 months, a CD4 count <250 cells/μl during chemotherapy is permitted as long as viral loads were undetectable during this same treatment period
  • They must have an undetectable viral load and a CD4 count ≥250 cells/μL within 7 days prior to Cycle 1 Day 1
  • They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months
  • Patients with active or uncontrolled infection, including hepatitis A, B or C. NOTE: Patients with controlled infection on antibiotic or antifungal therapy are eligible i.e. the patient should be afebrile for at least 72 hours and be haemodynamically stable.
  • Participation in another clinical study with an investigational product or another systemic therapy administered within 3 weeks prior to Cycle 1 Day 1.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Australia5 sites
  • Box Hill Hospital

    Box Hill, Victoria, 3128

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

  • Royal Melbourne Hospital

    Melbourne, Victoria, 3000

  • Alfred Hospital

    Prahran, Victoria, 3000

  • St Vincent's Hospital Sydney

    Sydney, New South Wales, 2010

Other trials in Australia

About this study

Official title: Phase 1 Trial of Pidnarulex and Talazoparib in Patients With Metastatic Castration Resistant Prostate Cancer

This is phase I, open label, multicentre, dose-escalation study where both doses of talazoparib and pidnarulex will be escalated to define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for the combination. It is possible that either 1 or 2 RP2D of the combination will be defined at the end of the study. Patients with disease that is deemed to be amendable to repeated tumour biopsies will be invited to undergo optional paired biopsies: at baseline and Cycle 1 Day 9 + 3 days and at the time of progression. Pidnarulex will be given as an IV infusion on days 1 and 8 of a 28 day cycle and talazoparib will be taken once daily continuously. Disease status will be assessed at regular intervals by CT scans, radionuclide bone scans, and PSA. Throughout the study, safety and tolerability will be assessed and established procedures for management of toxicities will be applied

Being tested
Pidnarulex, Talazoparib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PidnarulexDrug

    Also called CX-5461

    Pidnarulex is a treatment that is designed to stop the action of a particular protein in the body called Polymerase I, that cancer cells rely on. Laboratory studies show that pidnarulex targets a process involving Polymerase I within cells, which can lead to a decrease in cancer growth. Pidnarulex has been shown to have some anticancer activity in ovarian cancer and haematological cancers.

  • TalazoparibDrug

    Talazoparib belongs to a class of drugs called PARP inhibitors, which is currently being used to treat various types of cancer. Talazoparib blocks the function of PARP, a protein that is involved in repairing DNA in cells. By stopping damaged DNA in cells from being repaired, this will lead to accumulation of DNA damage in the cancer cell and ultimately cancer cell death. Talazoparib has established anticancer activity in breast, ovarian and prostate cancers with underlying DNA repair defects. This class of drug have also been used in combination with other treatments such as radiation or chemotherapy to further increase cell death within the cancer.

Study groups in NCT05425862
Study groupRoleWhat they receive
Treatment with both talazoparib and pidnarulexExperimentalAt the time of registration, patients will be assigned to the specific dose-schedule of talazoparib and pidnarulex depending on where the study is at in terms of dose-escalation or dose-expansion
Receives: Drug: Pidnarulex; Drug: Talazoparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The MTD is defined as the highest tolerable dose of pidnarulex when talazoparib is given at the highest tolerable dose and the highest dose of pidnarulex when talazoparib is given at the lowest dose (two MTDs will be estimated).

    Measured: From study start to end of 2 years of recruitment period.

Secondary outcomes (8)
  1. Safety will be measured by serious adverse events (SAEs) and adverse events (AEs) assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.

    Measured: From the time of signing consent until 28 days after the last dose of protocol treatment.

  2. Prostate Surface Antigen (PSA) response will be defined as a 50% or greater decrease in PSA from baseline to the lowest post-baseline PSA result. A second consecutive value obtained 4 or more weeks later confirms the PSA response.

    Measured: From Cycle 1 Day 1 of treatment until the date of first documented progression, assessed up to 36 months.

  3. Radiographic Progression Free Survival (rPFS)

    The radiographic progression will be assessed by the Investigator per RECIST1.1 for soft tissue and PCWG3 for bone lesions. A patient who begins a new systemic anti-cancer treatment for clinical progression without documented radiographic progression will be censored at the time of initiation of new treatment. For patients alive who have no radiographic progression, the time will be censored at the date of last radiographic evaluation. The time will be censored at the date of treatment initiation for patients with no post-baseline radiographic evaluation.

    Measured: From Cycle 1 Day 1 of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

  4. Prostate Surface Antigen Progression Free Survival (PSA-PFS).

    Measured: From Cycle 1 Day 1 of treatment until the date of first documented PSA progression or date of death from any cause, whichever came first, assessed up to 36 months.

  5. Overall response (OR) is only applicable for the subset of patients with measurable disease by RECIST1.1.

    Measured: From Cycle 1 Day 1 of treatment to the time of subsequent systemic anti-cancer treatment, assessed up to 36 months.

  6. Overall survival (OS)

    Measured: From Cycle 1 Day 1 of treatment to the date of death due to any cause, assessed up to 36 months.

  7. Duration of Response Prostate Cancer Working Group 3 (DOR-PCWG3)

    (Patients who died of non-cancer causes without progression will be censored on the date of their last tumour assessment. A patient who begins a new systemic anticancer treatment for clinical progression without documented radiographic progression per RECIST1.1 for soft tissue and PCWG3 for bone lesions will be censored at the time of initiation of new treatment).

    Measured: 12 weeks from Cycle 1 Day 1 of treatment to date of first documented radiographic progression. Assessed up to 36 months.

  8. Treatment discontinuation at any time due to treatment related toxicity for each patient.

    Measured: From study start to the end of study treatment. An average of 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2022
  2. Study start21 Oct 2022
  3. Primary completion1 Oct 2025
  4. Study completion1 Oct 2025

Why it stopped: It was decided to stop the study due to changes in the treatment landscape.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is phase I, open label, multicentre, dose-escalation study where both doses of talazoparib and pidnarulex will be escalated to define the MTD and RP2D for the combination.
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05425862
Sponsor's protocol ID
20/019
Acronym
REPAIR
Status last verified
Oct 2026
First submitted
10 Jun 2022
Last updated
2 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pidnarulex and Talazoparib in people with Metastatic Castration Resistant Prostate Cancer (mCRPC), run by Peter MacCallum Cancer Centre, Australia at 5 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: It was decided to stop the study due to changes in the treatment landscape.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The MTD is defined as the highest tolerable dose of pidnarulex when talazoparib is given at the highest tolerable dose and the highest dose of pidnarulex when talazoparib is given at the lowest dose (two MTDs will be estimated). (time frame: From study start to end of 2 years of recruitment period.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.

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