Cmet-46. Initial Clinical and Advanced Imaging Outcomes From a Multi-institutional Phase I Dose-escalation Trial of Rrx-001 Plus Whole Brain Radiation for Patients With Brain Metastases
Year: 2018
Type: conference-abstract
Abstract: RRx-001, a novel redox modulator was evaluated as a potential radiosensitizer with WBRT in a multicenter phase I trial for adults with brain metastases. The primary endpoint was to determine MTD. Secondary endpoints included intracranial response rate (IRR), survival and correlation of DCE-MRI parameters with outcome. Dose-escalation was managed by a TITE-CRM design to establish MTD at a 20% estimated DLT rate with four planned dose levels (5, 8.4, 16.5, 27.5 mg/m2). RRx-001 was given pre-WBRT (30 Gy/10 fractions) then twice weekly during WBRT. Target accrual was 30 patients. Correlative DCE-MRI was performed in a subset of patients at baseline, 24 hours post-RRx pre-WBRT, 1 and 4 months. Linear mixed models were used to correlate baseline and change in 24-hour Vp (plasma volume) with change in tumor volume. Between 2/2015-2/2017, 31 patients were enrolled across 5 centers. Two patients dropped out at baseline, and seven were treated with RRx/concurrent temozolomide to be reported separately, for a total of 22 evaluable patients. Median age was 60 years (range 35–85), 13 were male, 55% had melanoma and 23% had NSCLC. No DLTs were observed within 28 days of treatment and 5 patients were treated at the highest dose level. IRR was 50%, five patients survived > 12 months, 3 were alive at last follow-up. Among 10 evaluable patients undergoing DCE-MRI with 64 total lesions at baseline, lower baseline Vp (p=0.002) and reduction in Vp at 24 hours (p=0.001) were associated with reduced tumor volume at 1 and 4 months. RRx-001+WBRT appears well-tolerated in adults with brain metastases, with several long-term survivors and IRR of 50%. Following a single dose of RRx, a reduction in Vp is associated with tumor response at 1 and 4 months, suggesting activity within tumor vasculature and utility as a biomarker of longer-term response.
Source: Neuro-Oncology
Authors: Michelle Kim, Hemant Parmar, Madhava Aryal, Matthew Schipper, Theresa Devasia, Santosh Kesari, Aki Morikawa, Daniel Spratt, Larry Junck, James Hayman, Theodore Lawrence, Christina Tsien, Robert Aiken, Sharad Goyal, Susan Knox, Scott Caroen, Corey Carter, Bryan Oronsky, Yue Cao, Christopher Lao
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2900365992