Pidnarulex and Talazoparib in Patients With Metastatic Castration Resistant Prostate Cancer (REPAIR)
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|ClinicalTrials.gov Identifier: NCT05425862|
Recruitment Status : Recruiting
First Posted : June 21, 2022
Last Update Posted : October 28, 2022
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Castration Resistant Prostate Cancer (mCRPC)||Drug: Pidnarulex Drug: Talazoparib||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Intervention 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)|
|Official Title:||Phase 1 Trial of Pidnarulex and Talazoparib in Patients With Metastatic Castration Resistant Prostate Cancer|
|Actual Study Start Date :||October 21, 2022|
|Estimated Primary Completion Date :||July 12, 2024|
|Estimated Study Completion Date :||December 30, 2025|
Experimental: Treatment with both talazoparib and pidnarulex
At 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
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.
Other Name: CX-5461
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.
- 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. ]
- 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. [ Time Frame: From the time of signing consent until 28 days after the last dose of protocol treatment. ]
- 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. [ Time Frame: From Cycle 1 Day 1 of treatment until the date of first documented progression, assessed up to 36 months. ]
- Radiographic Progression Free Survival (rPFS) [ Time Frame: 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 ]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.
- Prostate Surface Antigen Progression Free Survival (PSA-PFS). [ Time Frame: 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. ]
- Overall response (OR) is only applicable for the subset of patients with measurable disease by RECIST1.1. [ Time Frame: From Cycle 1 Day 1 of treatment to the time of subsequent systemic anti-cancer treatment, assessed up to 36 months. ]
- Overall survival (OS) [ Time Frame: From Cycle 1 Day 1 of treatment to the date of death due to any cause, assessed up to 36 months. ]
- Duration of Response Prostate Cancer Working Group 3 (DOR-PCWG3) [ Time Frame: 12 weeks from Cycle 1 Day 1 of treatment to date of first documented radiographic progression. Assessed up to 36 months. ](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).
- Treatment discontinuation at any time due to treatment related toxicity for each patient. [ Time Frame: From study start to the end of study treatment. An average of 18 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05425862
|Contact: Shahneen Sandhu||+6138559 firstname.lastname@example.org|
|Peter MacCallum Cancer Centre||Recruiting|
|Melbourne, Victoria, Australia, 3000|
|Contact: Shahneen Sandhu|
|Principal Investigator:||Shahneen Sandhu||Peter MacCallum Cancer Research|