eprintid: 10160783 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/16/07/83 datestamp: 2022-11-29 15:28:41 lastmod: 2022-11-29 15:28:41 status_changed: 2022-11-29 15:28:41 type: article metadata_visibility: show sword_depositor: 699 creators_name: Merrick, Sophie creators_name: Nankivell, Matthew creators_name: Quartagno, Matteo creators_name: Clarke, Caroline S creators_name: Joharatnam-Hogan, Nalinie creators_name: Waddell, Tom creators_name: O'Carrigan, Brent creators_name: Seckl, Michael creators_name: Ghorani, Ehsan creators_name: Banks, Emma creators_name: Edmonds, Kim creators_name: Bray, George creators_name: Woodward, Rose creators_name: Bennett, Rachel creators_name: Badrock, Jonathan creators_name: Hudson, Will creators_name: Langley, Ruth E creators_name: Vasudev, Naveen creators_name: Pickering, Lisa creators_name: Gilbert, Duncan C title: REFINE (reduced frequency ImmuNE checkpoint inhibition in cancers): A multi-arm phase II basket trial testing reduced intensity immunotherapy across different cancers ispublished: inpress divisions: UCL divisions: B02 divisions: D12 divisions: G20 keywords: REFINE, Renal cancer, Immune checkpoint inhibitor, MAMS, Platform trial note: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ abstract: 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. date: 2022-11 date_type: published publisher: Elsevier BV official_url: https://doi.org/10.1016/j.cct.2022.107030 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1992309 doi: 10.1016/j.cct.2022.107030 lyricists_name: Clarke, Caroline lyricists_id: CSCLA53 actors_name: Clarke, Caroline actors_id: CSCLA53 actors_role: owner full_text_status: public publication: Contemporary Clinical Trials article_number: 107030 citation: Merrick, Sophie; Nankivell, Matthew; Quartagno, Matteo; Clarke, Caroline S; Joharatnam-Hogan, Nalinie; Waddell, Tom; O'Carrigan, Brent; ... Gilbert, Duncan C; + view all <#> Merrick, Sophie; Nankivell, Matthew; Quartagno, Matteo; Clarke, Caroline S; Joharatnam-Hogan, Nalinie; Waddell, Tom; O'Carrigan, Brent; Seckl, Michael; Ghorani, Ehsan; Banks, Emma; Edmonds, Kim; Bray, George; Woodward, Rose; Bennett, Rachel; Badrock, Jonathan; Hudson, Will; Langley, Ruth E; Vasudev, Naveen; Pickering, Lisa; Gilbert, Duncan C; - view fewer <#> (2022) 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 , Article 107030. 10.1016/j.cct.2022.107030 <https://doi.org/10.1016/j.cct.2022.107030>. (In press). Green open access document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10160783/1/2022%20Merrick%20ContempCT%20refine%20protocol%20paper%20preproof.pdf