Randomised phase III trial of the hypoxia modifier nimorazole added to radiotherapy with benefit assessed in hypoxic head and neck cancers determined using a gene signature (NIMRAD)
Name:
Randomized Phase 3....pdf
Size:
975.7Kb
Format:
PDF
Description:
Found with Open Access Button
Authors
Thomson, David JSlevin, Nick
Baines, H
Betts, G
Bolton, Steve
Evans, M
Garcez, Kate
Irlam, J
Lee, Lip
Melillo, N
Mistry, H
More, E
Nutting, PC
Price, James
Schipani, S
Sen, M
Yang, H
West, PCNTG
Affiliation
The Christie NHS Foundation Trust, Manchester, United KingdomIssue Date
2023
Metadata
Show full item recordAbstract
BACKGROUND: Tumour hypoxia is an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). We assessed whether patients with hypoxic HNSCC benefited from the addition of nimorazole to definitive intensity-modulated radiotherapy (IMRT). METHODS: NIMRAD was a phase III, multi-centre, placebo controlled, double-anonymized trial in patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive IMRT (NCT01950689). Patients were randomized 1:1 to receive IMRT (65 Gy in 30 fractions over 6 weeks) plus nimorazole (1.2 g/m2 daily, prior to IMRT) or placebo. The primary endpoint was freedom from loco-regional progression (FFLRP) in patients with hypoxic tumours, defined as greater than or equal to the median tumour hypoxia score of the first 50 patients analysed (≥0.079), using a validated 26-gene signature. The planned sample size was 340 patients allowing for signature generation in 85%, assumed HR 0.50 for nimorazole effectiveness in the hypoxic group, and requiring 66 loco-regional failures to have 80% power in a two-tail log-rank test at the 5% significance level. RESULTS: 338 patients were randomised by 19 UK centres from May 2014 to May 2019, with a median follow-up of 3.1 years (95%CI 2.9-3.4). Hypoxia scores were available for 286 (85%). The median patient age was 73 years (range: 44-88, IQR: 70-76). There were 36 (25.9%) loco-regional failures in the hypoxic group, where nimorazole + IMRT did not improve FFLRP (adjusted HR 0.72; 95% CI 0.36-1.44; p=0.35), or overall survival (adjusted HR 0.96; 0.53-1.72; p=0.88) compared with placebo + IMRT. Similarly, nimorazole + IMRT did not improve FFLRP or OS in the whole population. In total (n=338), 73% of patients allocated nimorazole adhered to the drug for ≥50% of IMRT fractions. Nimorazole + IMRT caused more acute nausea compared with placebo + IMRT (CTCAE v4.0 G1+2: 56.6% vs 42.4%, G3: 10.1% vs 5.3%, respectively; p<0.05). CONCLUSIONS: Addition of the hypoxia modifier nimorazole to IMRT for locally advanced HNSCC in older and less fit patients did not improve loco-regional control or survival.Citation
Thomson PD, Slevin PN, Baines H, Betts G, Bolton S, Evans PM, et al. Randomised phase III trial of the hypoxia modifier nimorazole added to radiotherapy with benefit assessed in hypoxic head and neck cancers determined using a gene signature (NIMRAD). International journal of radiation oncology, biology, physics. 2023 Dec 8. PubMed PMID: 38072326. Epub 2023/12/11. eng.Journal
International Journal of Radiation Oncology Biology PhysicsDOI
10.1016/j.ijrobp.2023.11.055PubMed ID
38072326Additional Links
https://dx.doi.org/10.1016/j.ijrobp.2023.11.055Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1016/j.ijrobp.2023.11.055
Scopus Count
Collections
Related articles
- IAEA-HypoX. A randomized multicenter study of the hypoxic radiosensitizer nimorazole concomitant with accelerated radiotherapy in head and neck squamous cell carcinoma.
- Authors: Hassan Metwally MA, Ali R, Kuddu M, Shouman T, Strojan P, Iqbal K, Prasad R, Grau C, Overgaard J
- Issue date: 2015 Jul
- Intensity-Modulated Reirradiation Therapy With Nivolumab in Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma: A Nonrandomized Controlled Trial.
- Authors: Saba NF, Wong SJ, Nasti T, McCook-Veal AA, McDonald MW, Stokes WA, Anderson AM, Ekpenyong A, Rupji M, Abousaud M, Rudra S, Bates JE, Remick JS, Joshi NP, Woody NM, Awan M, Geiger JL, Shreenivas A, Samsa J, Ward MC, Schmitt NC, Patel MR, Higgins KA, Teng Y, Steuer CE, Shin DM, Liu Y, Ahmed R, Koyfman SA
- Issue date: 2024 Jul 1
- Locally advanced head and neck cancer treated with accelerated radiotherapy, the hypoxic modifier nimorazole and weekly cisplatin. Results from the DAHANCA 18 phase II study.
- Authors: Bentzen J, Toustrup K, Eriksen JG, Primdahl H, Andersen LJ, Overgaard J
- Issue date: 2015 Jul
- Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial.
- Authors: Machiels JP, Tao Y, Licitra L, Burtness B, Tahara M, Rischin D, Alves G, Lima IPF, Hughes BGM, Pointreau Y, Aksoy S, Laban S, Greil R, Burian M, Hetnał M, Delord JP, Mesía R, Taberna M, Waldron JN, Simon C, Grégoire V, Harrington KJ, Swaby RF, Zhang Y, Gumuscu B, Bidadi B, Siu LL, KEYNOTE-412 Investigators
- Issue date: 2024 May
- Prognostic biomarkers for the response to the radiosensitizer nimorazole combined with RCTx: a pre-clinical trial in HNSCC xenografts.
- Authors: Koi L, Bitto V, Weise C, Möbius L, Linge A, Löck S, Yaromina A, Besso MJ, Valentini C, Pfeifer M, Overgaard J, Zips D, Kurth I, Krause M, Baumann M
- Issue date: 2023 Aug 26