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

Marcelo Bonomi, Dukagjin M. Blakaj, Rafi Kabarriti, Kyle Colvett, Vinita Takiar, Matthew Biagioli, Voichita Bar-Ad, Sharad Goyal, Brian Muzyka, Kenneth Niermann, Nacer Abrouk, Bryan Oronsky, Tony Reid, Scott Caroen, Stephen Sonis, David J. Sher

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Purpose: No Food and Drug Administration-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 that affects key pathways involved in OM pathogenesis. This phase 2a, multi-institutional trial was designed to assess the safety and feasibility of 3 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 and Materials: This study enrolled patients with oral cavity and oropharynx squamous cell carcinoma receiving definitive or postoperative cisplatin-based CRT. Patients were randomized into 4 cohorts. In arms 1 to 3, RRx-001 was coinfused 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 World Health Organization criteria. Safety outcomes were assessed using National Cancer Institute - Common Terminology Criteriav4 benchmarks. Long-term tumor response was defined by Response evaluation criteria in solid tumors 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 3 active arms, the study drug was infused fully per protocol in 86% of patients. All 3 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 1 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.

Original languageEnglish (US)
Pages (from-to)551-559
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number3
StatePublished - Jul 1 2023

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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