PREVLAR: Phase 2a randomized trial to assess the safety and efficacy of RRx-001 in the attenuation of oral mucositis in patients receiving head and neck chemoradiotherapy
International journal of radiation oncology, biology, physics
RRx-001; head and neck cancer; oral mucositis; priming; radiation therapy
INTRODUCTION: No FDA-approved intervention exists for oral mucositis (OM) from chemoradiotherapy (CRT) used to treat head and neck cancers. RRx-001 is a hypoxia-activated, cysteine-directed molecule which impacts key pathways involved in OM pathogenesis. This Phase 2a, multi-institutional trial was designed to assess the safety and feasibility of three schedules of a fixed concentration of RRx-001; a standard-of-care arm was included to identify potential signals of efficacy for further study. METHODS: This study enrolled patients with oral cavity and oropharynx squamous cell carcinoma receiving definitive or postoperative cisplatin-based CRT. Patients were randomized into four cohorts. In arms 1-3, RRx-001 was co-infused with patients' blood at differing intervals. Arm 4 was a control cohort of patients treated with CRT alone. Trained evaluators assessed OM using a standardized data collection instrument twice weekly during treatment and then until resolution. OM severity was scored centrally using WHO criteria. Safety outcomes were assessed using NCI-CTCv4 benchmarks. Long-term tumor response was defined by RECIST v1.1 criteria. RESULTS: Fifty-three patients were enrolled, with 46 and 45 individuals contributing safety and efficacy data, respectively. There were no severe adverse events attributed to the study drug. Across all three active arms, the study drug was infused fully per protocol in 86% of patients. All three RRx-001 treatment cohorts appeared to demonstrate a similar or lower OM duration relative to control; Arm 1 had the lowest median duration of severe oral mucositis (SOM), 8.5 days versus 24 days in controls among patients who developed at least one day of SOM . There were no locoregional failures in any patient. CONCLUSIONS: Our results support the safety and feasibility of RRx-001 as an intervention to mitigate SOM. Additional studies are planned to confirm its efficacy.
Bonomi, RuMarcelo; Blakaj, Dukagjin M.; Kabarriti, Rafi; Colvett, Kyle; Takiar, Vinita; Biagioli, Matthew; Bar-Ad, Voichita; Goyal, Sharad; Muzyka, Brian; Niermann, Kenneth; Abrouk, Nacer; Oronsky, Bryan; Reid, Tony; Caroen, Scott; Sonis, Stephen; and Sher, David J., "PREVLAR: Phase 2a randomized trial to assess the safety and efficacy of RRx-001 in the attenuation of oral mucositis in patients receiving head and neck chemoradiotherapy" (2023). GW Authored Works. Paper 2270.