Phase 1 dose escalation study of rigosertib by 2-, 4-, or 8-hour infusion twice-weekly in patients with advanced cancer.

Context: Rigosertib, a potent, multi-kinase inhibitor that selectively induces mitotic arrest and apoptosis in cancer cells and is non-toxic to normal cells, is being developed for the treatment of solid tumors and hematological malignancies.

Aims: To determine the safety, dose-limiting toxicities, and clinical activity of rigosertib administered by 2-, 4-, or 8-hour continuous IV infusion twice-a-week for 3 weeks out of a 4-week cycle in patients with advanced solid tumor or hematological malignancies; and to confirm the safety and tolerability of the recommended phase 2 dose (RPTD).

Settings And Design: Phase 1, open-label, dose-escalation study in men and women ≥18 years of age.

Materials And Methods: An escalation phase optimized the duration of infusion (2, 4, or 8 hours) of 3200 mg rigosertib twice-a-week for 3 weeks of a 4-week cycle; an expansion phase confirmed the maximum tolerated dose (MTD).

Statistical Analysis Used: All data summaries were descriptive. PK parameters were estimated using compartmental analysis.

Results: 25 patients (16 male, 9 female, 26-66 years, all Asian) were treated with rigosertib, 16 in the escalation phase; 9 in the expansion phase. MTD was determined to be 3200 mg as a 4-hour infusion and 2400 mg over 4 hours was declared to be the RPTD. Best response was stable disease in 5 of 14 evaluable patients, with a mean (range) of 90 (43-108) days.

Conclusions: 2400 mg rigosertib as a 4-hour infusion was identified as the RPTD. Five patients achieved stable disease lasting 6-16 weeks.