Nimoral (nimorazole) / Norgine, Hikma - LARVOL DELTA

A prospective randomized multicenter trial of Nimorazole as hypoxic modifier of accelerated chemo-radiotherapy for locally advanced HPV-neg HNSCC. (ESTRO 2025) - "Total Cisplatin dose was 200 mg/m2 either weekly (40 mg/m2 on week 1 to 5) or 3-weekly (100 mg/m2 on weeks 1 & 4). Despite the reduced patient number, NIM was found to improve locoregional control in advanced HPV-neg HNSCC, but without significant improvement in DSS or OS. This underlines that hypoxic modification is still active in concomitant chemo-radiotherapy of squamous cell carcinoma. The incompleteness of the study precludes analysis of the predictive value of the hypoxic-gene signature."

Clinical • Metastases • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

DAHANCA19: A randomized phase III study of primary curative (chemo)-radiotherapy and the EGFR-inhibitor zalutumumab for squamous cell carcinoma of the head and neck. (PubMed, Radiother Oncol) - "Addition of concomitant zalutumumab to primary (chemo-)radiotherapy and concomitant nimorazole for HNSCC did not increase locoregional control nor disease-specific or overall survival."

Journal • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

QoLATI: Quality of Life After Primary TORS vs IMRT for Patients With Early-stage Oropharyngeal Squamous Cell Carcinoma (clinicaltrials.gov) - P=N/A | N=138 | Active, not recruiting | Sponsor: Christian von Buchwald | Recruiting ➔ Active, not recruiting

Enrollment closed • HEOR • Head and Neck Cancer • Infectious Disease • Oncology • Oropharyngeal Cancer • Otorhinolaryngology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Repurposing radiosensitising medicines for radiotherapy: an overview. (PubMed, BMJ Oncol) - "Two compounds, nicotinamide and nimorazole, have entered routine but limited clinical use in combination with radiotherapy...Upon reviewing the trials, we identified some common themes behind the unsuccessful efforts, including poor trial reporting, absence of biomarkers and patient selection, sub-optimal pharmacological properties, inappropriate trial design, lack or inadequate consideration of pre-clinical and clinical data, and limited funding support. We point out future directions to mitigate these issues and increase the likelihood of success in repurposing drug treatments for radiotherapy."

Journal • Review • Oncology

Evaluating deposited radiation energy amount and collision quantities of small-molecule radiosensitizers through Monte Carlo simulations. (PubMed, Heliyon) - "This study investigates the photon interaction mechanism of various small molecule radiosensitizers, including Hydrogen Peroxide, Nimorazole, 5-Fluorouracil, NVX-108, and others, using the MCNP 6.3 Monte Carlo simulation code. The study also examined the individual attenuation properties of these radiosensitizers against energetic photons, with NVX-108 showing the highest attenuation coefficient and a shorter mean free path, further supporting its superior potential in effective radiosensitization. It can be concluded that NVX-108 has higher interaction tendency with the energetic photons comparing other small-molecules under investigation."

Journal • Oncology

Transcriptomic and epigenetic landscape of nimorazole-enhanced radiochemotherapy in head and neck cancer. (PubMed, Radiother Oncol) - "In the present study, we found that nimorazole non-responder models were characterized by upregulation of genes involved in Retinol metabolism and xenobiotic metabolic process pathways, which might contribute to identify mechanisms of resistance to nitroimidazole compounds and potentially expand the repertoire of therapeutic options to treat HNSCC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

The effect of primary radiotherapy in oropharynx cancer: A phase IV population-based DAHANCA study (ESTRO 2024) - "These observations indicate that deintensification of treatment entails the risk of compromising patient outcome, as was also observed in three randomized trials substituting cisplatin with EGFR-inhibition in the treatment of p16-pos OPSCC (1-3)...In addition, all radiobiological modifications were found to be independently associated with better outcomes: hypoxic modification with nimorazole (LRF: 0.74 [0.59-0.92], DFS: 0.69 [0.58-0.81]), accelerated fractionated RT (LRF: 0.58 [0.40-0.83], DFS: HR: 0.67 [0.50-0.89]) and concurrent chemotherapy (LRF: 0.62 [0.51-0.76], DFS: HR: 0.54 [0.47-0.63]), Figure 2... Our findings represent real-life data obtained through application of a uniform, nationwide treatment strategy consisting of primary RT with radiobiological intensifications, in a national cohort of more than 3400 OPSCC patients. We observe acceptable outcomes in the overall cohort and confirm the favorable prognosis for patients with p16-positive disease...."

Clinical • P4 data • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

High-dose loco-regional pattern of failure after primary radiotherapy in p16 positive and negative head and neck squamous cell carcinoma - A DAHANCA 19 study. (PubMed, Clin Transl Radiat Oncol) - "Patients with HNSCC of the oral cavity, oropharynx (OPSCC), hypopharynx or larynx were treated with primary curative IMRT (+/-cisplatin) and concomitant nimorazole between 2007 and 12. Radioresistance is the primary cause of failure after RT for HNSCC irrespective of HPV/p16 status. Thus, focus on predictors for the response to RT is warranted to identify patients with higher risk of high-dose failure that might benefit from intensified treatment regimens."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Optimizing Head and Neck Cancer Radiotherapy using '5+5 mm' DAHANCA Radiotherapy Guidelines (ICHNO 2024) - "Cox regression analysis indicated that factors such as sex (female), tumour site (HPV p16+ oropharyngeal), T stage (T1-2), treatment schedule (6 or 10 fractions per week), and the administration of nimorazole and chemotherapy were associated with superior three-year LC...Most recurrences occurred within CTV1 and were encompassed by the prescribed dose. A relevant next step could involve randomised trials comparing standard radiotherapy protocols with reduced margins and escalated doses to CTV1, further exploring the potential benefits of geometrically-based treatment strategies."

Head and Neck Cancer • Hypopharyngeal Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Tumor volume and cancer stem cell expression as prognostic markers for high-dose loco-regional failure in head and neck squamous cell carcinoma - a DAHANCA 19 study. (PubMed, Radiother Oncol) - "Tumor volume, p16, and CSC markers are potential biomarkers for HDF for patients with HNSCC treated with (C-)RT. Lower expression of CSC in p16+ OPSCC may contribute to better tumor control."

Biomarker • Cancer stem • Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD44 • SLC3A2

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). (PubMed, Int J Radiat Oncol Biol Phys) - P3 | "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."

Gene Signature • Journal • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Accelerated loss of lean body mass in head and neck cancer patients during cisplatin-based chemoradiation. (PubMed, Acta Oncol) - P=N/A | "48 patients (all tumor sites) received either 6 weeks of radiation alone (n = 16) with 66-68 Gy in 33-34 Fx, 5-6 Fx/week or CCRT, adding weekly cisplatin or carboplatin (n = 32)...Analyses adjusting for nimorazole, tumor stage, baseline BMI, mean radiation dose to constrictor muscles and oral cavity confirmed this...Patients receiving CCRT experienced significantly larger LBM loss than patients receiving radiation alone. Registered on clinincaltrials.gov (Identifier: NCT05890859)."

Journal • Head and Neck Cancer • Mucositis • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Prognostic biomarkers for the response to the radiosensitizer nimorazole combined with RCTx: a pre-clinical trial in HNSCC xenografts. (PubMed, J Transl Med) - "Nimorazole combined with RCTx improved local tumor control in some but not in all HNSCC xenografts. We identified prognostic biomarkers with the potential for translation to patients with HNSCC."

Journal • Preclinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Circinate Balanitis In Sexually Adquired Reactive Arthritis With Trichomonas Vaginalis Urethritis In Men (WCD 2023) - "In literature only two reports imply Trichomonas vaginalis association with RA, in both anti-inflammatory treatments failed to relieve symptoms but patients were cured with Antiparasitic treatment (nimorazole and metronidazole)...Urethral swab with Gram coloration is performed, evidencing in both cases the presence of Trichomonas vaginalis and in one case an association with Non-Gonococcal Infection. KEY MESSAGES: Circinate balanitis, Reiter’s syndrome, Sexually Acquired Reactive Arthritis, Trichomonas vaginalis"

Conjunctivitis • Dermatology • Immunology • Infectious Disease • Inflammatory Arthritis • Novel Coronavirus Disease • Ocular Infections • Ocular Inflammation • Ophthalmology • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • HLA-B

Radiation Therapies in Cancer. (PubMed, Cancer Treat Res) - "Specific chemotherapies are combined with radiation in the treatment of cancer after proper preclinical assessment of their effectiveness. Some classes of compounds include platinum-based drugs, antimicrotubules, antimetabolites (5-Fluorouracil, Capecitabine, Gemcitabine, Pemetrexed), topoisomerase I inhibitors, alkylating agents (Temozolomide), and other agents (Mitomycin-C, Hypoxic Sensitizers, Nimorazole)."

Journal • Oncology

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). (ASCO 2023) - P3 | " NIMRAD was a phase III, multi-centre, placebo-controlled, double-blind trial in patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive RT (NCT01950689). Addition of the hypoxia modifier nimorazole to RT for locally advanced HNSCC in older and less fit patients did not improve loco-regional control or survival. Clinical trial information: NCT01950689. >"

Clinical • Gene Signature • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Design, Synthesis and Anticancer Evaluation of Nitroimidazole Radiosensitisers. (PubMed, Molecules) - "Only nimorazole is used clinically as a radiosensitiser, and there is a dearth of new radiosensitisers in development. In this report, we augment previous work to present new nitroimidazole alkylsulfonamides and we document their cytotoxicity and ability to radiosensitise anoxic tumour cells in vitro. We compare radiosensitisation with etanidazole and earlier nitroimidazole sulfonamide analogues and we identify 2-nitroimidazole and 5-nitroimidazole analogues with marked tumour radiosensitisation in ex vivo assays of surviving clonogens and with in vivo tumour growth inhibition."

Journal • Oncology

Nimorazole Provides No Benefit in Head and Neck Cancers With Tumor Hypoxia (Cancer Therapy Advisor) - P3 | N=338 | NIMRAD (NCT01950689) | "Adding nimorazole to definitive radiotherapy does not improve outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who have tumor hypoxia, results from the phase 3 NIMRAD trial suggest....There was no significant difference in disease-free survival between the treatment arms in patients with more hypoxic tumors (HR, 0.99; 95% CI, 0.60-1.64; P =.98) or in the overall cohort (HR, 1.00; 95% CI, 0.73-1.37; P =.98). There was no significant difference in cancer-specific survival between the treatment arms in patients with more hypoxic tumors (HR, 0.89; 95% CI, 0.44-1.80; P =.75) or in the overall cohort (HR, 0.92; 95% CI, 0.60-1.42; P =.72)."

P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Tumor volume and cancer stem cells as prognostic markers for loco-regional control in HNSCC (ESTRO 2023) - "Treatment was primary curative IMRT-based (C-)RT (66-68Gy/33-34fx 6 fx/wk (+/- cisplatin 40mg/m2 weekly)) and nimorazole. Conclusion Tumor volume was prognostic for the non-HPV-driven tumors only. In contrast to volume, the level of CSC was prognostic in OPSCCp16+, which may benefit in selection of pts for individualized treatment."

Biomarker • Cancer stem • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • SLC3A2

Target and failure pattern in SCC-HNCUP: a prospective phase-4 study from DAHANCA (ESTRO 2023) - "Concomitant chemotherapy was cisplatin (40 mg/m2 weekly). Seventy percent of patients treated with primary (C)RT received concurrent nimorazole...Loco-regional failures are described in relation to planned CTVs. The loco-regional control was acceptable and comparable to primary head and neck SCC in other sites."

Clinical • P4 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Early and substantial decline in lean body mass during (chemo)radiation in HNC patients (ECHNO-ICHNO 2023) - "This difference was confirmed in analyses adjusted for tumour site, stage, nimorazole and baseline BMI. Conclusion Lean body mass declined significantly and substantially in HNC patients before the onset of radiation-induced side effects, such as mucositis, suggesting that LBM depends on multiple factors including concurrent cisplatin. Loss of LBM was correlated significantly with loss of muscle strength. The present findings emphasize the importance of early and prophylactic interventions to combat LBM loss, e.g., nutritional support and onset of resistance training; particularly in patients treated with concomitant chemoradiation."

Clinical • Head and Neck Cancer • Mucositis • Oncology • Solid Tumor

Activity of Drug Combinations against Mycobacterium abscessus Grown in Aerobic and Hypoxic Conditions. (PubMed, Microorganisms) - "Out of 18 drugs tested, 14-day treatments with bedaquiline-amikacin (BDQ-AMK)-containing three-drug combinations were very active against A1 + H5 cells. Instead, 56-day treatments with the nitrocompounds containing combinations BDQ-AMK-rifabutin-clarithromycin-nimorazole and BDQ-AMK-rifabutin-clarithromycin-metronidazole-colistin killed all A1 + H5 Mab cells in 42 and 56 days, respectively, as shown by lack of regrowth in agar and MGIT medium. Overall, these data indicated that Mab persisters may be killed by appropriate drug combinations."

Journal • Bronchiectasis • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Non‐Cystic Fibrosis Bronchiectasis • Nontuberculous Mycobacterial Disease • Pulmonary Disease • Respiratory Diseases

Bound Electron Enhanced Radiosensitisation of Nimorazole upon Charge Transfer. (PubMed, Molecules) - "Quantum chemical calculations on the electronic structure of NIMO in the presence of a potassium atom were performed to help assign the most significant lowest unoccupied molecular orbitals participating in the collision process. Electron transfer was shown to be a relevant process for nimorazole radiosensitisation through efficient and prevalent non-dissociated parent anion formation."

Journal

Feasibility of Patient Selection and Treatment of Head-neck Cancer With Proton Therapy in Denmark (clinicaltrials.gov) - P=N/A | N=63 | Active, not recruiting | Sponsor: Danish Head and Neck Cancer Group

New trial • Head and Neck Cancer • Oncology • Solid Tumor