December 11 2020
Phase I Trial with Expansion Cohort of DNA-PK Inhibition and IMRT in Cisplatin-Ineligible Patients with Stage 3-4 Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)
NRG Oncology activated the clinical trial NRG-HN008 in December 2020. This phase I trial will evaluate the safety of adding the DNA-Protein Kinase inhibitor, peposertib, to radiotherapy for patients with advanced head and neck cancer who cannot tolerate cisplatin. Researchers will be determining the maximum tolerated dose and recommended phase II dose of peposertib when combined with definitive intensity-modulated radiotherapy (IMRT). Typically, patients with this type of cancer are treated with standard of care chemoradiotherapy.
“Although, cisplatin-based chemoradiotherapy has proven effective in improving survival outcomes for advanced head and neck cancer patients when compared to radiotherapy, cisplatin is commonly associated with nausea, renal dysfunction and ototoxicity. The latter two toxicities may be permanent for some patients.NRG-HN008 was developed as a means to find a safer yet similarly effective treatment for this patient population,” stated Maura Gillison, MD, PhD, of the University of Texas MD Anderson Cancer Center and Co-Principal Investigator for the NRG-HN008 trial.
“Cisplatin is believed to be effective for patients with advanced head and neck cancer primarily through its action as a radiosensitizer. Peposertib is a rationally-designed radiosensitizer that targets the most important mechanism of sublethal damage repair and can enhance the effect of radiation, especially on tumor cells, without the toxicities typically seen with cisplatin.NRG-HN008 is an important step in a broader effort to determine if peposertib could eventually replace cisplatin in combination with radiation therapy,” added Michael Samuels, MD, of the University of Miami Sylvester Comprehensive Cancer Center and Co-Principal Investigator for the NRG-HN008 trial.
Additionally, study researchers will be evaluating the safety and tolerability of the peposertib and IMRT combination, rates of grade 3 or higher acute toxicities, late toxicities, 6-and 12-month progression-free survival, and 6- and 12-month overall survivals in this phase I trial.
The data from this safety evaluation will inform the design of future trials comparing peposertib-IMRT to cisplatin-IMRT to evaluate the efficacy of the treatment.
Learn more about this trial on ClinicalTrials.gov
The protocol, consent form, and patient brochure are located on the CTSU website. All other protocol related documents are available on the NRG Oncology website.