The standard treatment for unresectable head and neck cancer typically involves radiotherapy (RT) alone or chemoradiotherapy (chemo-RT). Non-squamous cell carcinomas exhibit relatively low radiosensitivity, limiting the efficacy of conventional photon RT. Carbon-ion (C-ion) RT, characterised by high linear energy transfer (LET) and high relative biological effectiveness (RBE), has shown promising outcomes in treating radioresistant head and neck cancers. However, local recurrences still occur, and further improvements in treatment outcomes are needed. To enhance the local control rate, an increase in dose-averaged LET (LETd) to the tumour was considered.

Following a simulation study, a clinical trial was conducted to optimise LETd using only C-ion therapy, and its safety was confirmed. However, in this clinical trial, LETd could only be increased to approximately 70 keV/μm. To further escalate LETd, multi-ion therapy using ions heavier than carbon was developed. Simulation studies demonstrated that multi-ion therapy incorporating carbon, oxygen and neon ions could increase LETd up to 90 keV/μm, regardless of tumour size, while maintaining high-dose uniformity within the tumour. Based on these results, a clinical study was planned to evaluate the safety of escalating LETd from 70 keV/μm to 90 keV/μm using multi-ion therapy. The primary objective of this study is to evaluate the safety of escalating LETd to the tumour using multi-ion therapy for head and neck cancer, with the secondary goal of identifying the maximum tolerated LETd.

This is a non-randomised, open-label, phase 1 study focused on LETd escalation. A maximum of 18 patients with histologically confirmed inoperable head and neck malignancies will be enrolled. All patients will receive multi-ion therapy using helium, carbon, oxygen or neon ions, either alone or in combination, at an RBE-weighted dose ranging from 57.6 to 70.4 Gy, delivered in 16 fractions (4 fractions per week) over 4 weeks. The specific dose will be determined according to histology. LETd escalation will begin at 70 keV/μm and will increase by 10 keV/μm increments, reaching a maximum of 90 keV/μm. The safety of multi-ion therapy will be assessed based on the frequency and severity of dose-limiting toxicities, monitored up to 90 days after the initial irradiation. Patients will be followed up according to the protocol for 180 days after the initial multi-ion therapy irradiation.

The study protocol has been approved by the National Institutes for Quantum Science and Technology Certified Review Board (#L24-002). The results will be published in a peer-reviewed journal and presented at a scientific conference.

jRCTs032240451.

Hepatitis C virus (HCV) remains a leading cause of infectious disease-related morbidity in the USA, disproportionately affecting people who inject drugs and people who are incarcerated. Despite the availability of highly effective, highly tolerated direct-acting antivirals, treatment uptake in jails remains limited due to short stays, unpredictable release dates and system-level barriers. The original MINMON trial demonstrated that a low barrier ‘minimal monitoring"’ model can achieve high cure rates in community settings. This study, MINMON-J, aims to adapt and evaluate a modified version of the MINMON model for use in a jail setting, addressing the urgent need for scalable, low-barrier treatment approaches among justice-involved individuals.

MINMON-J is a single-arm, hybrid effectiveness-implementation pilot study protocol planned to recruit at the Rhode Island Department of Corrections. 40 people who are incarcerated with positive HCV RNA, who are treatment-naïve, without cirrhosis and awaiting trial, will receive 12 weeks of sofosbuvir/velpatasvir with no required lab monitoring during treatment. If released before treatment completion, participants will receive their remaining medication at discharge. Community health workers will provide post-release support. Mixed-methods evaluation will be guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance/Practical, Robust Implementation and Sustainability Model framework. Primary outcomes include feasibility, acceptability and adherence. Data will be collected through administrative records, surveys (Acceptability of Intervention Measure, Feasibility of Intervention Measure, Brief Adherence Rating Scale) and qualitative interviews with participants and other relevant parties. This study was reviewed and approved by the Brown University Health Institutional Review Board (2240400) and the Rhode Island Department of Corrections Medical Research Advisory Group.

This study was reviewed and approved by the Brown University Health Institutional Review Board (2240400) and the Rhode Island Department of Corrections (RIDOC) Medical Research Advisory Group. All participants will provide written informed consent prior to enrolment. People who are incarcerated will be assured that participation is voluntary, will not impact their clinical care and that they may withdraw at any time without penalty. Study procedures follow ethical principles outlined in the Declaration of Helsinki and comply with federal regulations regarding research involving vulnerable populations.

Dissemination of findings will include peer-reviewed publications and presentations at national conferences focused on infectious diseases, implementation science and/or correctional health. Lay summaries will be shared with RIDOC leadership and community partners. De-identified data and associated metadata may be archived in a publicly accessible repository in accordance with National Institutes of Health data sharing policies, contingent on final institutional review board approval and participant protections.

NCT06953479.