{
  "abstract": "Introduction To date, there is no proven licensed systemic treatment for neurofibromatosis type 2 (NF2)-related schwannomatosis patients. There is a need for more effective, less toxic treatments and, as a rare disease, NF2 is often overlooked in targeted drug development. Subcutaneous schwannomas of the skin (CS) are common in the NF2 population.This trial involves the repurposing of medications already licensed for HIV—ritonavir and lopinavir (Kaletra and Norvir)—that have been shown to reduce tumour growth by reducing cell proliferation in human schwannoma and meningioma tumour cell cultures. The safety and tolerability of these drugs are already known, so they are safe candidates to trial in NF2 patients.Methods and analysis This trial is an open-label, phase 0 design. A maximum of 16 participants diagnosed with NF2-related schwannomatosis will be enrolled in this study. Treatment duration is 30 days, with a 30-day follow-up. Biopsies and blood samples will be collected to assess whether the drugs reach the tumours and to analyse the tumour-cell response. The primary outcome is pharmacodynamic response, defined as a statistically significant decrease in biomarker activity in CS biopsy samples at day 30. The sample size calculation is based on the tissue biomarker response.Ethics and dissemination The study was approved by an Ethics Committee (West of Scotland Research Ethics Service (23/WS/0178)), the Health Research Authority (HRA), the Medicines and Healthcare products Regulatory Authority (MHRA) and each of the participating NHS Trust’s Research and Development departments. Following analysis of trial data, the trial results will be written up for publication in a peer-reviewed scientific journal and will be disseminated at conferences.Trial registration number ISRCTN10422213.",
  "authors": [
    {
      "affiliations": [
        "University of Plymouth, Plymouth, UK"
      ],
      "name": "Sarah Campbell"
    },
    {
      "affiliations": [
        "University of Plymouth, Plymouth, UK"
      ],
      "name": "Katherine Beaney"
    },
    {
      "affiliations": [
        "University of Plymouth, Plymouth, UK"
      ],
      "name": "Joanne Hosking"
    },
    {
      "affiliations": [
        "University of Plymouth, Plymouth, UK"
      ],
      "name": "Lexy Sorrell"
    },
    {
      "affiliations": [
        "University of Plymouth, Plymouth, UK"
      ],
      "name": "Victoria Allgar"
    },
    {
      "affiliations": [
        "University of Plymouth, Plymouth, UK"
      ],
      "name": "Paigan J Aspinall"
    },
    {
      "affiliations": [
        "University of Plymouth, Plymouth, UK"
      ],
      "name": "Sylwia Ammoun"
    },
    {
      "affiliations": [
        "Manchester University NHS Foundation Trust, Manchester, UK"
      ],
      "name": "D Gareth Evans"
    },
    {
      "affiliations": [
        "University of Plymouth, Plymouth, UK"
      ],
      "name": "C O Hanemann"
    },
    {
      "affiliations": [
        "University of Plymouth, Plymouth, UK",
        "University Hospitals Plymouth NHS Trust, Plymouth, UK"
      ],
      "name": "Sarah Kingdon"
    }
  ],
  "title": "Repurposing anti-retroviral drugs to treat NF2-related tumours: a protocol for a phase 0 trial (RETREAT)",
  "uid": "e9334749-0d87-56b1-b887-9ff2874d99d3"
}