REFINE (REduced Frequency ImmuNE checkpoint inhibition in cancers): A multi-arm phase II basket trial testing reduced intensity immunotherapy across different cancers
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Authors
Merrick, S.Nankivell, M.
Quartagno, M.
Clarke, C. S.
Joharatnam-Hogan, N.
Waddell, Thomas
O'Carrigan, B.
Seckl, M.
Ghorani, E.
Banks, E.
Edmonds, K.
Bray, G.
Woodward, R.
Bennett, R.
Badrock, J.
Hudson, W.
Langley, R. E.
Vasudev, N.
Pickering, L.
Gilbert, D. C.
Affiliation
MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, 2nd Floor 90 High Holborn, London WC1V 6LJ, UIssue Date
2022
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Background: Immune checkpoint inhibitors (ICI) have revolutionised treating advanced cancers. ICI are administered intravenously every 2-6 weeks for up to 2 years, until cancer progression/unacceptable toxicity. Physiological efficacy is observed at lower doses than those used as standard of care (SOC). Pharmacodynamic studies indicate sustained target occupancy, despite a pharmacological half-life of 2-3 weeks. Reducing frequency of administration may be possible without compromising outcomes. The REFINE trial aims to limit individual patient exposure to ICI whilst maintaining efficacy, with potential benefits in quality of life and reduced drug treatment/attendance costs. Methods/design: REFINE is a randomised phase II, multi-arm, multi-stage (MAMS) adaptive basket trial investigating extended interval administration of ICIs. Eligible patients are those responding to conventionally dosed ICI at 12 weeks. In stage I, patients (n = 160 per tumour-specific cohort) will be randomly allocated (1:1) to receive maintenance ICI at SOC vs extended dose interval. REFINE is currently recruiting UK patients with locally advanced or metastatic renal cell carcinoma (RCC) who have tolerated and responded to initial nivolumab/ipilimumab, randomised to receive maintenance nivolumab SOC (480 mg 4 weekly) vs extended interval (480 mg 8 weekly). Additional tumour cohorts are planned. Subject to satisfactory outcomes (progression-free survival) stage II will investigate up to 5 different treatment intervals. Secondary outcome measures include overall survival, quality-of-life, treatment-related toxicity, mean incremental pathway costs and quality-adjusted life-years per patient. REFINE is funded by the Jon Moulton Charity Trust and Medical Research Council, sponsored by University College London (UCL), and coordinated by the MRC CTU at UCL.Citation
Merrick S, Nankivell M, Quartagno M, Clarke CS, Joharatnam-Hogan N, Waddell T, et al. REFINE (REduced Frequency ImmuNE checkpoint inhibition in cancers): A multi-arm phase II basket trial testing reduced intensity immunotherapy across different cancers. Contemporary clinical trials. 2022 Nov 26;124:107030. PubMed PMID: 36519749. Epub 2022/12/16. eng.Journal
Contemporary Clinical TrialsDOI
10.1016/j.cct.2022.107030PubMed ID
36519749Additional Links
https://dx.doi.org/10.1016/j.cct.2022.107030Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1016/j.cct.2022.107030
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