Tolerability of concurrent external beam radiotherapy and [177Lu]Lu-PSMA-617 for node-positive prostate cancer in treatment naïve patients, phase I study (PROQURE-I trial)

• Published in: BMC cancer Vol. 23; no. 1; pp. 268 - 13
• Main Authors: van der Sar, Esmée C. A., Braat, Arthur J. A. T., van der Voort- van Zyp, Jochem R. N., van der Veen, Betty S., van Leeuwen, Pim J., de Vries-Huizing, Daphne M. V., Hendrikx, Jeroen M. A., Lam, Marnix G. E. H., Vogel, Wouter V.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 23.03.2023; BioMed Central; BMC
• Subjects: Acute toxicity; Analysis; Androgen Antagonists - therapeutic use; Bayes Theorem; Bayesian analysis; Bladder; Cancer; Cancer patients; Cancer therapies; Care and treatment; Castration; Clinical trials; Complications and side effects; Dipeptides - adverse effects; Drug therapy; Exocrine glands; Heterocyclic Compounds, 1-Ring - adverse effects; Humans; Hypotheses; Lu-PSMA; Lymph nodes; Lymphatic diseases; Lymphatic system; Male; Medical prognosis; Metastases; Metastasis; Nausea; Node-positive; Oncology, Experimental; Patient outcomes; Patients; Pharmacokinetics; Prognosis; Prospective Studies; Prostate cancer; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - radiotherapy; Quality of Life; Radiation therapy; Radiotherapy; Study Protocol; Systemic diseases; Terminology; Thrombocytopenia; Treatment Outcome; Tumors; Netherlands; Node-positive; Prostate cancer; Lu-PSMA
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-023-10725-5

Prostate cancer patients with locoregional lymph node disease at diagnosis (N1M0) still have a limited prognosis despite the improvements provided by aggressive curative intent multimodal locoregional external beam radiation therapy (EBRT) with systemic androgen deprivation therapy (ADT). Although some patients can be cured and the majority of patients have a long survival, the 5-year biochemical failure rate is currently 29-47%. [ Lu]Lu-PSMA-617 has shown impressive clinical and biochemical responses with low toxicity in salvage setting in metastatic castration-resistant prostate cancer. This study aims to explore the combination of standard EBRT and ADT complemented with a single administration of [ Lu]Lu-PSMA-617 in curative intent treatment for N1M0 prostate cancer. Hypothetically, this combined approach will enhance EBRT to better control macroscopic tumour localizations, and treat undetected microscopic disease locations inside and outside EBRT fields. The PROQURE-I study is a multicenter prospective phase I study investigating standard of care treatment (7 weeks EBRT and 3 years ADT) complemented with one concurrent cycle (three, six, or nine GBq) of systemic [ Lu]Lu-PSMA-617 administered in week two of EBRT. A maximum of 18 patients with PSMA-positive N1M0 prostate cancer will be included. The tolerability of adding [ Lu]Lu-PSMA-617 will be evaluated using a Bayesian Optimal Interval (BOIN) dose-escalation design. The primary objective is to determine the maximum tolerated dose (MTD) of a single cycle [ Lu]Lu-PSMA-617 when given concurrent with EBRT + ADT, defined as the occurrence of Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grade three or higher acute toxicity. Secondary objectives include: late toxicity at 6 months, dosimetric assessment, preliminary biochemical efficacy at 6 months, quality of life questionnaires, and pharmacokinetic modelling of [ Lu]Lu-PSMA-617. This is the first prospective study to combine EBRT and ADT with [ Lu]Lu-PSMA-617 in treatment naïve men with N1M0 prostate cancer, and thereby explores the novel application of [ Lu]Lu-PSMA-617 in curative intent treatment. It is considered likely that this study will confirm tolerability as the combined toxicity of these treatments is expected to be limited. Increased efficacy is considered likely since both individual treatments have proven high anti-tumour effect as mono-treatments. ClinicalTrials, NCT05162573 . Registered 7 October 2021.