BRAINSTORM: A Multi-Institutional Phase 1/2 Study of RRx-001 in Combination With Whole Brain Radiation Therapy for Patients With Brain Metastases.
International journal of radiation oncology, biology, physics
PURPOSE: To determine the recommended phase 2 dose of RRx-001, a radiosensitizer with vascular normalizing properties, when used with whole-brain radiation therapy (WBRT) for brain metastases and to assess whether quantitative changes in perfusion magnetic resonance imaging (MRI) after RRx-001 correlate with response.
METHODS AND MATERIALS: Five centers participated in this phase 1/2 trial of RRx-001 given once pre-WBRT and then twice weekly during WBRT. Four dose levels were planned (5 mg/m
RESULTS: Between 2015 and 2017, 31 patients were enrolled. Two patients dropped out before any therapy. Median age was 60 years (range, 30-76), and 12 were male. The most common tumor types were melanoma (59%) and non-small cell lung cancer (18%). No dose limiting toxicities were observed. The most common severe adverse event was grade 3 asthenia (6.9%, 2 of 29). The median intracranial response rate was 46% (95% confidence interval, 24-68) and median overall survival was 5.2 months (95% confidence interval, 4.5-9.4). No neurologic deaths occurred. Among 10 patients undergoing dynamic contrast-enhanced MRI, a reduction in Vp 24 hours after RRx-001 was associated with reduced tumor volume at 1 and 4 months (P ≤ .01).
CONCLUSIONS: The addition of RRx-001 to WBRT is well tolerated with favorable intracranial response rates. Because activity was observed across all dose levels, the recommended phase 2 dose is 10 mg twice weekly. A reduction in fractional plasma volume on dynamic contrast-enhanced MRI 24 hours after RRx-001 suggests antiangiogenic activity associated with longer-term tumor response.
Kim, Michelle M; Parmar, Hemant A; Schipper, Matthew; Devasia, Theresa; Aryal, Madhava P; Kesari, Santosh; O'Day, Steven J; Morikawa, Aki; Spratt, Daniel E; Junck, Larry; Mammoser, Aaron; Hayman, James A; Lawrence, Theodore S; Tsien, Christina I; Aiken, Robert; Goyal, Sharad; Abrouk, Nacer; Trimble, Malcolm; Cao, Yue; and Lao, Christopher D, "BRAINSTORM: A Multi-Institutional Phase 1/2 Study of RRx-001 in Combination With Whole Brain Radiation Therapy for Patients With Brain Metastases." (2020). Articles, Abstracts, and Reports. 3008.