A phase II study of oxaliplatin reintroduction in patients pretreated with oxaliplatin and irinotecan for advanced colorectal cancer (RE-OPEN study): Reports of interim analysis.

Abstract

580 Background: Re-introduction of oxaliplatin for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens including oxaliplatin, irinotecan and fluorouracil (5-FU) was thought to be effective approach, but has not been prospectively explored. Thus, we performed a single arm, open-label phase II study (UMIN ID: 000004884). Methods: Patients with prior chemotherapy including oxaliplatin and irinotecan, achieved tumor response or stable disease during prior oxaliplatin-based therapy, and six months or over from confirmed progression disease during previous oxaliplatin-based therapy were eligible for this study. Patients received FOLFOX regimens every two weeks. Primary endpoint was disease control rate (DCR) after 12 weeks of treatment. Tumor response was evaluated by RECIST v1.1, and DCR was defined as complete response, partial response or stable disease. This trial followed a Simon’s two-stage minimax design. Interim analysis of efficacy was planned after 12 weeks of treatment in 18 patients (Step I). If disease control were confirmed in more than five patients, 15 patients would be newly enrolled in Step II. Results: Between 01-2011 and 07-2012, 18 patients were enrolled in Step I of this study. Characteristics of patients were as follows (N=18): median age, 61 yrs (range 35-75 yrs); male/female, 11/7; ECOG PS0, 94.4%; and colon/rectum, 8/10. All patients were assigned to receive mFOLFOX6 regimen. Disease control was observed in seven patients. There was no benefit in nine patients. Two patients refused to continue treatment and one patient gave up treatment due to oxaliplatin related allergic reaction. According to the interim analysis, DCR after 12 weeks of treatment was 38.9%. There were no severe adverse events and treatment related deaths. Conclusions: In interim analysis, initial efficacy of reintroduction of oxaliplatin after 12 weeks of FOLFOX regimen was confirmed. Step II part of this study is currently ongoing. Clinical trial information: UMIN000004884.