ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901)

Autor: Arun Azad, Shalini Subramaniam, Andrew J. Martin, Sonia Yip, Ian D. Davis, Alison Yan Zhang, Ailsa Langford, Louise Emmett, Anthony M. Joshua, Jenna Mitchell, Martin R. Stockler, Craig Gedye, Roslyn J. Francis, Margaret McJannett, Megan Crumbaker, Nisha Rana, Michael S Hofman, Shahneen Sandhu
Rok vydání: 2021
Předmět:
Oncology
Glutamate Carboxypeptidase II
Male
medicine.medical_specialty
Urology
medicine.medical_treatment
Cost-Benefit Analysis
Gallium Radioisotopes
Lutetium
Prostate cancer
chemistry.chemical_compound
Heterocyclic Compounds
1-Ring
Clinical Trials
Phase II as Topic
Fluorodeoxyglucose F18
Internal medicine
Positron Emission Tomography Computed Tomography
Antineoplastic Combined Chemotherapy Protocols
Nitriles
Phenylthiohydantoin
medicine
Clinical endpoint
Enzalutamide
Humans
Multicenter Studies as Topic
Molecular Targeted Therapy
Adverse effect
Gallium Isotopes
Response Evaluation Criteria in Solid Tumors
Randomized Controlled Trials as Topic
Radioisotopes
Chemotherapy
medicine.diagnostic_test
business.industry
Hazard ratio
Dipeptides
Prostate-Specific Antigen
medicine.disease
Prognosis
Progression-Free Survival
Clinical trial
Survival Rate
Prostatic Neoplasms
Castration-Resistant
chemistry
Positron emission tomography
Antigens
Surface
Benzamides
Quality of Life
Radiopharmaceuticals
business
Zdroj: BJU internationalReferences. 128(5)
ISSN: 1464-410X
Popis: Objectives To determine the activity and safety of lutetium-177 (177 Lu)-prostate-specific membrane antigen (PSMA)-617 in men with metastatic castration-resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression, and to identify potential prognostic and predictive biomarkers from imaging, blood and tissue. Participants and methods ENZA-p (ANZUP 1901) is an open-label, randomized, two-arm, multicentre, phase 2 trial. Participants are randomly assigned (1:1) to treatment with enzalutamide 160 mg daily alone or enzalutamide plus 177 Lu-PSMA-617 7.5 GBq on Days 15 and 57. Two additional 177 Lu-PSMA-617 doses are allowed, informed by Day-92 Gallium-68 (68 Ga)-PSMA positron emission tomography (PET; up to four doses in total). The primary endpoint is prostate-specific antigen (PSA) progression-free survival (PFS). Other major endpoints include radiological PFS, PSA response rate, overall survival, health-related quality of life, adverse events and cost-effectiveness. Key eligibility criteria include: biochemical and/or clinical progression; 68 Ga-PSMA PET-avid disease; no prior androgen signalling inhibitor, excepting abiraterone; no prior chemotherapy for mCRPC; and ≥2 high-risk features for early enzalutamide failure. Assessments are 4 weekly during study treatment, then 6 weekly until radiographic progression. Response Evaluation Criteria in Solid Tumours (RECIST) are used to assess imaging conducted every 12 weeks, 68 Ga-PSMA PET at baseline, Days 15 and 92, and at progression, and 18 F-fluorine deoxyglucose (18 F-FDG) PET at baseline and progression. Translational samples include blood (and optional biopsies) at baseline, Day 92, and first progression. Correlative studies include identification of prognostic and predictive biomarkers from 68 Ga-PSMA and 18 F-FDG PET/CT, circulating tumour cells and circulating tumour DNA. The trial will enrol 160 participants, providing 80% power with a two-sided type-1 error rate of 5% to detect a hazard ratio of 0.625 assuming a median PSA-PFS of 5 months with enzalutamide alone. Results and conclusion The combination of 177 Lu-PSMA-617 and enzalutamide may be synergistic. ENZA-p will determine the safety and efficacy of the combination in addition to developing predictive and prognostic biomarkers to better guide treatment decisions.
Databáze: OpenAIRE
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