Time to disease progression in children with relapsed or refractory neuroblastoma treated with ABT-751: A report from the Children's Oncology Group (ANBL0621)

• Published in: Pediatric blood & cancer Vol. 61; no. 6; pp. 990 - 996
• Main Authors: Fox, Elizabeth, Mosse', Yael P., Meany, Holly M., Gurney, James G., Khanna, Geetika, Jackson, Hollie A., Gordon, Gary, Shusterman, Suzanne, Park, Julie R., Cohn, Susan L., Adamson, Peter C., London, Wendy B., Maris, John M., Balis, Frank M.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.06.2014; Wiley Subscription Services, Inc
• Subjects: Adolescent; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Biomarkers; Capsules; Child; Child, Preschool; childhood cancer; clinical trial; Combined Modality Therapy; Disease Progression; Disease-Free Survival; Female; Gastrointestinal Diseases - chemically induced; Hematologic Diseases - chemically induced; Hematology; Humans; Male; microtubule inhibitor; Nervous System Diseases - chemically induced; neuroblastoma; Neuroblastoma - drug therapy; Neuroblastoma - therapy; Oncology; Pediatrics; Quality of Life; Recurrence; Salvage Therapy; Sulfonamides - adverse effects; Sulfonamides - pharmacokinetics; Sulfonamides - therapeutic use; Suspensions; time to progression; Treatment Failure; Tubulin Modulators - therapeutic use; clinical trial; neuroblastoma; childhood cancer; time to progression; microtubule inhibitor
• ISSN: 1545-5009; 1545-5017; 1545-5017
• DOI: 10.1002/pbc.24900

Background ABT‐751, an orally bioavailable sulfonamide binds the colchicine site of beta‐tubulin and inhibits microtubule polymerizaton. Prior phase I studies established the recommended dose in children with solid tumors as 200 mg/m2 PO daily × 7 days every 21 days and subjects with neuroblastoma experienced prolonged stable disease. We conducted a phase 2 study (NCT00436852) in children and adolescents with progressive neuroblastoma to determine if ABT‐751 prolonged the time to progression (TTP) compared to a hypothesized standard based on a historical control population. Procedure Children and adolescents (n = 91) with a median (range) age 7.7 (2.3–21.5) years and progressive neuroblastoma were enrolled and stratified by disease status into disease measureable by CT/MRI (n = 47) or disease assessable by 123I‐metaiodobenzylguanine scintigraphy (MIBG, n = 44). Response was evaluated using RECIST for measureable disease and the Curie score for MIBG‐avid disease. Results ABT‐751 was well tolerated. The objective response rate was 7%. The median TTP was 42 days (95% CI: 36, 56) in the measureable disease stratum and 45 days (95% CI: 42, 85) in the MIBG‐avid disease stratum. TTP was similar to the historical control group (n = 136, median TTP 42 days). For the combined strata (n = 91), 1‐year progression free survival (PFS) was 13 ± 4% and overall survival (OS) was 48 ± 5%. Conclusions The low objective response rate and failure to prolong TTP indicate that ABT‐751 is not sufficiently active to warrant further development for neuroblastoma. However, this trial demonstrates the utility of TTP as the primary endpoint in phase 2 trials in children and adolescents with neuroblastoma. Pediatr Blood Cancer 2014;61:990–996. © 2013 Wiley Periodicals, Inc.