MEDSIR has begun enrollment in ZZ-First: "A randomized phase II trial to evaluate the antitumor activity of Enzalutamide and Talazoparib (PF-06944076) for the treatment of metastatic hormone-naïve prostate cancer", with the first patient starting to receive treatment at Hospital Virgen de la Victoria de Málaga, Spain on 14-Oct-2020.
ZZ-First study is a multicenter, open-label, randomized, two-arm, phase II clinical trial is focused in to explore the possibility to expand the population benefiting from PARP inhibition beyond patients with DDR genomic defects, and prolong the clinical benefit from patients receiving enzalutamide, delaying emergence of clinical progression. For this purpose, several tissues and blood samples are requested throughout the study to perform translational studies to assess the correlation between molecular and transcriptomic signatures of deoxyribonucleic acid (DNA) repair function and antitumor activity in this population.
The primary objective is to evaluate the antitumor activity of talazoparib (PF-06944076) in combination with enzalutamide and ADT –as determined by the confirmed prostate-specific antigen-complete response (PSA-CR)– in patients with mHNPC.
Some inclusion/exclusion criteria are:
- Histologically confirmed adenocarcinoma of the prostate without predominance of small-cell or neuroendocrine features according to ASCO/CAP guidelines based on local testing on the most recently analyzed biopsy.
- High-volume metastatic disease documented on bone scan or computed tomography (CT) /magnetic resonance imaging (MRI) scan, defined as the presence or either visceral disease and /or at least four bone metastases on bone scan, with at least one of them beyond spine/pelvis.
- Patients must have evaluable or measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
- Willingness and ability to provide tumor paired biopsies during the study participation to perform exploratory studies.
- ECOG 0-1
- PSA ≥ 4 ng/mL at diagnosis or before starting ADT therapy
- Prior treatment with enzalutamide, apalutamide, darolutamide or abiraterone acetate.
- Prior systemic therapy for metastatic prostate cancer (mPCa).
Note: Initiation of androgen deprivation therapy (ADT) within 4 weeks before study entry would be allowed (with or without first-generation antiandrogens), providing a tumor biopsy sample was taken prior to initiation of ADT is made available for biomarker studies and upon approval by the sponsor. If a patient was started on first-generation antiandrogens, these would be discontinued before randomization.
Note: Patients relapsing after having received an ADT-based regimen in neoadjuvant or adjuvant setting will be suitable for the study if metastatic progression occurred while on non-castrate testosterone levels or at least 12 months after discontinuation of ADT
- Known or suspected brain metastases or active leptomeningeal disease
This trial will enroll a total of 54 patients in Spain during an estimated recruitment period of 17 months.
The participating sites of the study are:
· Hospital Universitari Vall D'Hebron
· Hospital Universitario Virgen de la Victoria
· Hospital Universitario Doce de Octubre
· Hospital Clínic i Provincial de Barcelona
· Hospital Universitario Miguel Servet
· Hospital Provincial de Castellón
· Instituto Valenciano de Oncología (IVO)
· Hospital del Mar
We truly appreciate all the work and effort the investigator team has put into setting-up the ZZ-First clinical trial.
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Author: Marta Martinez