Comparing High- and Low-Dose Cisplatin for Patients with Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck (NRG-HN009)

November 11 2021

NRG-HN009: Randomized Phase II/III Trial of Radiation with High-dose Cisplatin (100 mg/m2) Every Three Weeks Versus Radiation with Low-dose Weekly Cisplatin (40 mg/m2) for Patients with Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Radiation combined with concurrent cisplatin is the standard of care non-surgical treatment for patients with advanced squamous cell carcinoma of the head and neck (SCCHN). However, the optimal dose/administration schedule for cisplatin remains controversial in this patient population. The two most common cisplatin schedules include 100 mg/m2 of cisplatin every three weeks during radiation therapy or 30-40 mg/m2 of cisplatin weekly during radiation therapy. Although both treatment regimens are commonly used worldwide, the preferred regimen with respect to overall survival outcome and toxicity profile remains ill-defined.

“NRG-HN009 was designed to clarify the optimal treatment dose and schedule for cisplatin use in SCCHN patients,” stated Paul M. Harari, MD, FASTRO, of the University of Wisconsin School of Medicine and Public Health and the Principal Investigator of the NRG-HN009 trial. “We know that many p16-positive oropharyngeal cancer (OPC) patients are younger with fewer medical co-morbidities and a significant opportunity to achieve long-term survival outcome, whereas p16-negative SCCHN patients are typically older, with more frequent co-morbidities and greater risk of experiencing toxicities associated with cisplatin chemotherapy. NRG-HN009 will examine whether low-dose weekly cisplatin is equal to or better than high-dose cisplatin given every three weeks for each of these subgroups of SCCHN patients in terms of toxicity burden and outcomes.”

NRG-HN009 is currently enrolling patients with advanced SCCHN of the oropharynx (OPC), larynx or hypopharynx to receive curative intent radiation to 70 Gy with concurrent cisplatin. Trial participants will be assigned to either the p16-positive OPC or HN unknown primary cohort or the non-OPC/p16-negative OPC cohort. Then patients will be stratified by Zubrod (ECOG) performance status, smoking status, t-stage, and age within cohort. Following stratification, patients will be randomly assigned within cohort to receive either intensity-modulated radiotherapy (IMRT) or intensity-modulated proton therapy (IMPT) with high-dose cisplatin (100 mg/m2) every 3 weeks or to receive IMRT/IMPT with low-dose (40 mg/m2) cisplatin weekly.

The Phase II portion of this trial will determine whether radiation therapy combined with weekly low-dose cisplatin is superior to high-dose cisplatin every 3 weeks in terms of acute toxicity. The Phase III portion of this trial will assess whether radiation therapy with low-dose cisplatin is not inferior to radiation therapy with high-dose cisplatin regarding overall survival, as well as whether the low-dose cisplatin treatment shows less acute toxicity. Secondary objectives of the trial include assessing progression-free survival, locoregional failure, distant metastasis, acute and late toxicity, patient-reported outcomes and quality of life, and hearing loss between treatment arms. Blood and tissue specimens will also be collected for future translational science studies.

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Protocol documents and materials are located on the CTSU website.

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