Enzalutamide Plus Talazoparib for the Treatment of Hormone Sensitive Prostate Cancer (ZZ-First)

NCT04332744 | Completed Phase 2 DMC

• 2 other identifiers: MedOPP2342019-003096-20
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 8

Brief Summary

This is a multicenter, open-label, randomized, two-arm, phase II clinical trial to evaluate the efficacy and safety of talazoparib (PF-06944076) in combination with enzalutamide in patients with metastatic hormone-naïve prostate cancer (mHNPC)

Conditions

Metastatic Prostate Cancer

Keywords

Prostate cancer; Metastatic prostate cancer; Hormone naïve; Unresectable prostate cancer; mHNPC; Prostate cancer stage IV; Prostatic neoplasm

Outcome Measures

Primary Outcomes (1)

• Prostate specific antigen complete response (PSA-CR)

  The primary efficacy endpoint for the study is the PSA-CR. The PSA-CR is defined as the percentage of patients with PSA \< 0.2 ng/mL divided by the number of patients in the analysis set.

  Baseline up to 12 months

Secondary Outcomes (9)

• Efficacy determined by Prostate specific antigen complete response (PSA-CR)

  Baseline up to 7 months

• Efficacy determined by PSA response

  Baseline up to 7 and 12 months

• Efficacy determined by Time to Clinical Progression (TCP)

  Baseline up to 12 months

• Efficacy determined by Prostate-Specific Antigen progression of disease (PSA-PD)

  Baseline up to 12 months

• Efficacy determined by Prostate-Specific Antigen progression-free survival (PSA-PFS)

  Baseline up to 12 months

Study Arms (2)

Control Arm (Arm A)

ACTIVE COMPARATOR

Patients will receive enzalutamide capsules orally once daily continuously (160 mg) in addition to standard ADT (unless surgical castration).

Drug: Enzalutamide

Interventional Arm (Arm B)

EXPERIMENTAL

Patients will receive enzalutamide capsules 160 mg in combination with talazoparib (PF-06944076) capsules 0.5 mg, both orally daily and continuously in 28-day cycle, in addition to standard ADT (unless surgical castration).

Drug: Enzalutamide; Drug: Talazoparib

Interventions

Enzalutamide DRUG

Enzalutamide capsules orally once daily and continuously (160 mg) in 28-day cycles (every four weeks)

Also known as: Xtandi

Control Arm (Arm A); Interventional Arm (Arm B)

Talazoparib DRUG

Talazoparib capsules orally once daily and continuously (0.5 mg) in 28-day cycles (every four weeks)

Also known as: (PF-06944076)

Interventional Arm (Arm B)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (\>18 y.o.) who signed informed consent form (ICF) prior to participation in any study-related activities.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• High-volume metastatic disease documented on bone scan or computed tomography (CT)/magnetic resonance imaging (MRI) scan, defined as the presence of either visceral disease and/or at least four bone metastases on bone scan, with at least one of them beyond spine/pelvis.
• Life expectancy of ≥ 12 months.
• Histologically confirmed adenocarcinoma of the prostate without predominance of small-cell or neuroendocrine features according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines based on local testing on the most recent analyzed biopsy.
• Note: Central confirmation of adenocarcinoma is not required for study entry. However, tissue blocks, or slides, must be submitted to confirm the diagnoses by a Sponsor-designated central laboratory retrospectively and/or exploratory biomarker analyses.
• Willingness and ability to provide tumor paired biopsies during the study participation in order to perform exploratory studies. At the study entry, the most recent tumor biopsy since last progression from either metastatic or primary tissues will be provided. If not feasible, patient eligibility should be evaluated by a Sponsor's qualified designee.
• Adequate hematologic and organ function within 28 days before the first study treatment on Cycle 1 Day 1, defined by the following:
• Hematological: White blood cell (WBC) count \> 3.0 x 109/L; Absolute neutrophil count (ANC) \> 1.5 x 109/L; Platelet count \> 100.0 x109/L; Hemoglobin (Hb) \> 9.0 g/dL.
• Note: Patients receiving growth factors or blood transfusions within 14 days before obtaining the hematology values at screening will be excluded.
• Hepatic: Total bilirubin ≤ 1.5 times the upper limit of normal (× ULN) (≤ 3 x ULN in the case of Gilbert's disease); Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (in the case of liver metastases ≤ 5 × ULN); Alkaline phosphatase (ALP) ≤ 2.5 × ULN (≤ 5 × ULN inthe case of liver and/or bone metastases).
• Renal: Serum creatinine \< 1.5 × ULN or creatinine clearance ≥ 30 mL/min based on Cockcroft-Gault glomerular filtration rate estimation.
• Coagulation: International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless on medication known to alter INR and/or aPTT.
• Nutritional status: Serum Albumin ≥ 2.8 g/dL.

You may not qualify if:

• Prior treatment with enzalutamide, apalutamide, darolutamide or abiraterone acetate.
• History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills.
• Known hypersensitivity to recombinant proteins, or any excipient contained in the drug formulation for talazoparib (PF-06944076) and enzalutamide.
• Prior systemic therapy for metastatic prostate cancer (mPCa). Note: Initiation of androgen deprivation therapy (ADT) within 4 weeks prior to 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 patient was started on first-generation antiandrogens, these would be discontinued on prior to 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 occured while on non-castrate testosterone levels or at least 12 months after discontinuation of ADT.
• Treatment with approved or investigational cancer therapy within 28 days (or 5 half-lives of the drug- whichever is longer) prior to initiation of study treatment.
• Known or suspected brain metastases or active leptomeningeal disease.
• Symptomatic or impending spinal cord compression or cauda equina syndrome.
• Subject has a history of seizure or any condition that may predispose to seizure (i.e. prior significant brain trauma, brain vascular malformations, ...), or subjects that have had unexplained loss of consciousness or transient ischemic attacks within 1 year prior to scheduled Day 1 of treatment.
• Therapeutic radiation therapy within 14 days (seven days for limited-field palliative radiotherapy) prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to grade ≤ 1 according to National Cancer Insitute ́s Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v.)5.0.
• Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 14 days of start of study drugs, or patients who have not recovered from the side effects of any major surgery.
• History of another malignancy within three years of study enrollment with the exception of carcinoma in situ, non-melanoma skin carcinoma, or American Joint Committee on Cancer stage 0 or stage 1 cancer that has a remote probability of recurrence in the opinion of the investigator and the Sponsor's Medical Monitor is required, or any concurrent malignancy for which the patient is receiving therapy.
• Active uncontrolled infection at the time of enrollment.
• Congenital long QT syndrome or Electrocardiogram (ECG) at screening with QT interval corrected using Fridericia's formula (QTcF) \> 500 milliseconds.
• Patients with clinically significant cardiovascular disease including but not limited to any of the following:

Sponsors & Collaborators

• MedSIR: lead
• Pfizer: collaborator

Study Sites (8)

Institut Català d'Oncologia Badalona

Badalona, Spain

Location

Hospital Clínic i Provicial de Barcelona

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Vall d'Hebrón

Barcelona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Instituto Valenciano de Oncología (IVO)

Valencia, Spain

Location

Hospital Universitario Miguel Sevet

Zaragoza, Spain

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; talazoparib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Joaquin Mateo

  VHIO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized 1:2

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 3, 2020
• Study Start: September 2, 2020
• Primary Completion: May 6, 2025
• Study Completion: May 6, 2025
• Last Updated: May 11, 2025

Record last verified: 2024-07

Locations

ES (8)