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Repurposing anti-retroviral drugs to treat NF2-related tumours: a protocol for a phase 0 trial (RETREAT)
Sarah Campbell1, Katherine Beaney2, Joanne Hosking1
1University of Plymouth, Plymouth, UK.
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.
Insights
This study investigates repurposing HIV drugs ritonavir and lopinavir for neurofibromatosis type 2 (NF2)-related schwannomatosis. The trial aims to assess if these drugs reduce tumor biomarker activity in patients with NF2.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Neurofibromatosis type 2 (NF2)-related schwannomatosis lacks approved systemic treatments.
- Existing licensed medications for HIV, ritonavir and lopinavir, show potential in reducing schwannoma and meningioma cell proliferation.
- Repurposing these known drugs offers a potentially safer and more accessible treatment avenue for NF2.
Purpose of the Study:
- To evaluate the efficacy of repurposed HIV medications (ritonavir and lopinavir) in NF2-related schwannomatosis.
- To assess the pharmacodynamic response and safety of these drugs in a phase 0 trial.
- To determine if these drugs can reach and impact tumor cells in patients with NF2.
Main Methods:
- An open-label, phase 0 clinical trial involving up to 16 participants with NF2-related schwannomatosis.
- A 30-day treatment period with ritonavir and lopinavir, followed by a 30-day follow-up.
- Collection of biopsies and blood samples to measure drug penetration and tumor-cell response, focusing on biomarker activity.
Main Results:
- The primary outcome is a statistically significant decrease in biomarker activity in cutaneous schwannoma (CS) biopsy samples at day 30.
- Pharmacodynamic response will be assessed based on tissue biomarker changes.
- Safety and tolerability data will be collected throughout the trial.
Conclusions:
- This trial will provide crucial data on the potential of repurposed HIV drugs for NF2 treatment.
- Findings may support the development of novel therapeutic strategies for this rare genetic disorder.
- Successful outcomes could lead to improved treatment options for patients with NF2-related schwannomatosis.
