Talazoparib Plus Enzalutamide After Progression to Prior ARPi in Metastatic Prostate Cancer
ConditionMetastatic Prostate Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexMale
Age18+
SponsorFundacion Oncosur
About this trial
The purpose of this clinical trial is to determine the anti-tumor activity of talazoparib plus enzalutamide as first line treatment for metastatic castration resistant prostate cancer (mCRPC) in participants whose disease has progressed on Androgen Receptor Pathway Inhibitor (ARPI).
The main questions it aims to answer are:
* Does talazoparib plus enzalutamide improve efficacy in metastatic castration resistant prostate cancer (mCRPC) compared to enzalutamide alone? * What is the time to disease progression \[radiographic, Prostate Specific Antigen (PSA), clinical\] in participants treated with talazoparib plus enzalutamide after progression on abiraterone? * What medical problems do participants have when receiving talazoparib plus enzalutamide?
Researchers will compare the combination of talazoparib and enzalutamide as a first-line treatment for mCRPC to see if the combination improves the PSA response rate and delays progression compared to enzalutamide alone. The safety and tolerability of the combination (talazoparib and enzalutamide) will also be studied
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Male age 18 or older.
Histological diagnosis of prostate adenocarcinoma without neuroendocrine differentiation or small cell features.
Willing and able to provide written informed consent to participate in the study. Written consent must be given before registration, according to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) / Good clinical practice (GCP), and national/local regulations.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Disqualifiers
Prior ARPi treatment for less than 12 weeks or disease progression (either PSA or radiographic progression) within 6 months of starting abiraterone or ARi.
Known or suspected brain metastasis or active leptomeningeal disease.
Symptomatic or impending spinal cord compression or cauda equina syndrome.
Use of opiate analgesia for pain from prostate cancer with average Brief pain inventory (BPI) questionnaire score higher than or equal to 6 and/or uncontrolled prostate cancer-related pain requiring increasing doses of opiates within 4 weeks prior to randomization
Trial design
Design model
Parallel
Treatments tested in this trial
Enzalutamide capsule
DrugEnzalutamide capsules 160 mg orally daily
Enzalutamide capsule and Talazoparib capsule
DrugEnzalutamide capsules 160 mg plus talazoparib capsules 0.5 mg, both orally daily
Treatment groups
78 Participants
are divided into 2 treatment groupsGroup A: ControlActive comparator 1 intervention
Group B: Enzalutamide and Talazoparib. Post-AA/ARi according to prior treatment.Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
PSA response (PSA50)
Percentage of participants with a PSA decline greater than or equal to 50 percent from baseline confirmed by a consecutive PSA value (taken at least 3 weeks apart), prior to PSA progression
Time frame
within the first 16 weeks2
Objective response rate (ORR)
Defined as the best overall radiographic response (partial or complete) during the first 16 weeks on follow up as per investigator assessment of soft tissue/visceral disease per RECIST 1.1 in subjects who have a measurable tumour and/or Prostate Cancer Working Group 3 (PCWG3) criteria for bone metastases
Time frame
during the first 16 weeksSecondary outcomes
1
Radiographic Progression Free Survival (rPFS)
Time from randomization to first objective evidence of radiographic progression, based on RECIST 1.1 for soft tissue/visceral disease and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines for bone metastases, or death, whichever occurs first.
Time frame
Through study completion, an average of 2 years2
Time to PSA Progression (TTPP)
Time from randomization to PSA progression defined as PSA greater than or equal to 25 percent and greater than or equal to 2ng/mL from nadir (or baseline for participants with no PSA decline), confirmed by a second value obtained 3 or more weeks apart as per PCWG3 guidelines.
Time frame
Through study completion, an average of 2 years3
Time to unequivocal clinical progression (TTCP)
Time from randomization to clinical worsening of prostate cancer related symptoms, as new onset cancer pain requiring chronic administration of opiate analgesia, deterioration from prostate cancer of Eastern Cooperative Oncology Group (ECOG) performance status score to 3 or higher, time to first skeletal-related event (the time from randomization to first incidence of radiotherapy to the bone or bone surgery, pathological bone fracture, spinal cord compression, or change of antineoplastic therapy to treat bone pain); or initiation of subsequent lines of active treatment including cytotoxic chemotherapy or radiation therapy or surgical intervention due to complications or symptoms related to disease progression.
Time frame
Through study completion, an average of 2 years4
Progression Free Survival (PFS)
Time from randomization to PSA progression, unequivocal clinical progression or radiographic progression, whichever occurs first.
Time frame
Through study completion, an average of 2 yearsOther outcomes
1
Assessment of PSA response rate
In participants with and without germline and/or somatic DDR alterations.
Time frame
Through study completion, an average of 2 years2
Assessment of ORR
In participants with and without germline and/or somatic DDR alterations
Time frame
Through study completion, an average of 2 years3
Assessment of rPFS
In participants with and without germline and/or somatic DDR alterations
Time frame
Through study completion, an average of 2 years4
Assessment of TTPP
In participants with and without germline and/or somatic DDR alterations.
Time frame
Through study completion, an average of 2 yearsSponsors and contacts
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Source ClinicalTrials.gov