Cancer-related cognitive impairment is frequently reported by patients with breast cancer after chemotherapy. These difficulties can hinder return to work. It is therefore particularly important to assess and manage these impairments, especially to facilitate employment. We propose the Cog-VR pilot study to assess patient adherence to a virtual reality (VR)-based cognitive rehabilitation programme to support employment.

This prospective interventional pilot study aims to assess adherence to a VR-based cognitive rehabilitation programme in patients with breast cancer (n=23) treated by chemotherapy reporting cognitive complaints following cancer and its treatments. The programme consists of six weekly individual sessions (1 hour/week), including cognitive training, psychoeducation and VR immersion (10–15 min). VR tasks train executive functions, attention, memory and processing speed. The primary endpoint is the programme adherence, defined as completing at least five out of six VR sessions, each lasting a minimum of 5 min. The main secondary endpoints are objective cognitive tests and patient-reported outcomes (subjective cognitive functioning (Functional Assessment of Cancer Therapy—Cognitive Scale), anxiety/depression (Hospital Anxiety and Depression Scale) and fatigue (Functional Assessment of Chronic Illness Therapy—Fatigue)) assessed before and after the programme. Furthermore, cyber sickness (Simulator Sickness Questionnaire) at each session, VR usability (System Usability Scale—third session) and patient satisfaction to the programme will also be assessed.

The study was approved by the local ethics committee (French Ouest II personal protection committee no. ID RCB: 2023-A02163-42) on January 2024. It was validated by the review board of the participating center. An individual participant data-sharing statement is not planned. Written informed consent will be obtained from all patients before any study procedure. The results of this pilot study will be disseminated through peer-reviewed journals and conference presentations.

NCT06267014.

Salvage prostatic bed radiotherapy (PBRT) is a standard in case of biochemical recurrence following radical prostatectomy (RP) for prostate cancer (PC). The management of isolated prostatic bed recurrence following RP and PBRT is debated. Reirradiation within stereotactic body radiotherapy (SBRT) guided by metabolic imaging could be a relevant option in this case. In parallel, metformin, an economically viable and well-tolerated oral antidiabetic agent, has demonstrated its radiosensitising properties. This phase I/II clinical trial aims to (i) determine the optimal dose for SBRT reirradiation, (ii) conduct safety assessments and (iii) evaluate the efficacy of the metformin and SBRT combination.

We conducted a prospective, non-randomised, open-label, multicentre, dose escalation, phase I/II study involving a minimum of 44 patients. Eligible patients must have biochemical recurrence (Prostate Specific Antigen (PSA)>0.2 ng/mL and confirmed ascending trend in at least two successive assays), occurring at least 2 years after PBRT and prior RP for PC (including low, intermediate and high risk with a single risk factor) and no Common Terminology Criteria for Adverse Events (CTCAE) grade>=2 toxicity following PBRT. The recurrence should be visible on MRI and/or Positron Emission Tomography (PET) Choline and/or PET PSMA, without evidence of pelvic lymph node recurrence or metastatic disease. The primary objective of phase I is to determine the optimal SBRT dose (5x6, 6x6, or 5x5 Gy) based on dose-limiting toxicity (DLT). The dose will be chosen using a time-to-event continual reassessment method based on DLT, defined as CTCAE grade ≥3 gastrointestinal or genitourinary toxicity, or any other grade 4 adverse event. The primary outcome of the phase II is to estimate the efficacy of SBRT in combination with metformin in terms of biological relapse-free survival (bRFS) rate at 3 years. Secondary outcomes include 5-year bRFS rate, early/late genitourinary and gastrointestinal toxicities, quality of life, biochemical response rate, clinical progression-free survival and overall survival (OS).

Ethical approval has been obtained from the Ethics committee "SUD EST III Bron" Ref.CPP 2020-042B (20.05.07.72735) and the National Agency for the Safety of Medicines (ANSM) Ref. ANSM MEDAECNAT-2020-05-00009. The ethics approval obtained covers all the sites that will take part in this study. The study’s findings will be disseminated through publications and conference presentations.

NCT04536805, Registration Date: 2020-08-17

Pain accounts for approximately 80% of emergency department admissions. While intravenous morphine titration is commonly used for severe pain, non-invasive alternatives that bypass intravenous access are needed. Nebulised fentanyl, combined with pupillometry for objective monitoring of opioid impregnation, may offer a rapid and safe alternative for pain management.

This phase I, open-label, randomised, exploratory, crossover, single-centre prospective controlled trial will employ pharmacokinetic–pharmacodynamic (PK–PD) modelling to assess the variability in bioavailability of nebulised fentanyl administered via intranasal route versus facial aerosol. 20 healthy volunteers will receive three repeated administrations of fentanyl over two visits. At each visit, blood samples (n=11) will be collected for fentanyl quantification by liquid chromatography–tandem mass spectrometry, and pupillary unrest in ambient light (PUAL) measurements (n=9) will be recorded. The resulting data will be analysed using Monolix 2024R1 to model PK–PD relationships, perform Monte Carlo simulations and determine the optimal dosing and timing required to achieve a reduction of more than 30% in PUAL, while also evaluating safety, comfort and tolerance.

The study has been approved by the Ethic Committee Île-de-France VII (approval reference number: 000216, February 2024) and will be conducted in accordance with the Declaration of Helsinki. Informed consent will be obtained from all participants. Study findings will be disseminated through peer-reviewed publications, conference presentations and appropriate data-sharing platforms to support further research and clinical application.

This trial is registered at ClinicalTrials.gov (Identifier: NCT06281951).