Phase 1b trial of proteasome inhibitor carfilzomib with irinotecan in lung cancer and other irinotecan-sensitive malignancies that have progressed on prior therapy (Onyx IST reference number: CAR-IST-553).
Investigational new drugs
Adolescent; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Irinotecan; Lung Neoplasms; Male; Maximum Tolerated Dose; Neoplasm Recurrence, Local; Oligopeptides; Proteasome Inhibitors
Introduction Proteasome inhibition is an established therapy for many malignancies. Carfilzomib, a novel proteasome inhibitor, was combined with irinotecan to provide a synergistic approach in relapsed, irinotecan-sensitive cancers. Materials and Methods Patients with relapsed irinotecan-sensitive cancers received carfilzomib (Day 1, 2, 8, 9, 15, and 16) at three dose levels (20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2/day) in combination with irinotecan (Days 1, 8 and 15) at 125 mg/m2/day. Key eligibility criteria included measurable disease, a Zubrod PS of 0 or 1, and acceptable organ function. Patients with stable asymptomatic brain metastases were eligible. Dose escalation utilized a standard 3 + 3 design. Results Overall, 16 patients were enrolled to three dose levels, with four patients replaced. Three patients experienced dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) was exceeded in Cohort 3. The RP2 dose was carfilzomib 20/36 mg/m
Earle A. Chiles Research Institute
Arnold, Susanne M; Chansky, Kari; Leggas, Markos; Thompson, Michael A; Villano, John L; Hamm, John; Sanborn, Rachel E; Weiss, Glen J; Chatta, Gurkamal; and Baggstrom, Maria Q, "Phase 1b trial of proteasome inhibitor carfilzomib with irinotecan in lung cancer and other irinotecan-sensitive malignancies that have progressed on prior therapy (Onyx IST reference number: CAR-IST-553)." (2017). Articles, Abstracts, and Reports. 2276.