Abstract CT137: A pilot pharmacokinetic study of VAL413 in patients with recurrent pediatric solid tumors

Abstract

Abstract Background: Ewing's sarcoma (EWS) is the second most common malignant bone tumor affecting children, adolescents and young adults. Intravenous irinotecan hydrochloride (IRN-IV) is approved for the treatment of adult colorectal cancer. IRN-IV is also widely used off-label as salvage therapy for patients with recurrent EWS, rhabdomyosarcoma, neuroblastoma, hepatoblastoma, and medulloblastoma. Prior adult and pediatric trials demonstrate that the combination of intravenous irinotecan and temozolomide has significant antitumor activity in advanced EWS. Recently, commercially available intravenous irinotecan has been administered orally (IRN-IVPO) in pediatric patients to reduce intravenous administration-related side effects, improve convenience and reduce clinic time and costs. Unfortunately, the taste of the iv preparation can be limiting, leading to poor compliance especially in pediatric patients. Development of an advanced formulation to improve tolerability and patient compliance is an important unmet need. Methods: VAL-413 is novel formulation developed to improve tolerability of oral irinotecan for the treatment of cancer. This study (USIND#135675) aims to establish the recommended phase II dose of VAL-413 when given in combination with temozolomide. Secondary objectives include characterization of the pharmacokinetics of VAL-413 vs. conventional irinotecan given orally (IRN-IVPO), evaluating palatability of VAL-413, assessing the toxicity profile of VAL-413 in combination with temozolomide, and assessment of tumor response. Up to 20 patients &gt= 1 to &lt= 30 years of age with recurrent pediatric solid tumors will be enrolled at two different dose levels of VAL-413 in combination with fixed-dose temozolomide using a standard 3 + 3 design. During the first cycle of treatment, each patient will receive 4 daily doses of VAL-413 and one daily dose of IRN-IVPO, together with 5 days of concurrent temozolomide. During all subsequent cycles, only VAL-413 will be given with temozolomide in 5-day courses administered every 21 days. Up to 17 cycles of treatment may be administered on this study. This study design will test the hypothesis that VAL-413 will not have significant pharmacokinetic differences from IRN-IVPO using intra-patient comparison of pharmacokinetic profiles. The evaluation of two dose levels will help to formally define a recommended Phase II dose for further studies. Toxicity will be evaluated based on CTCAEv5 and tumor response based on RECISTv1.1. Citation Format: James I. Geller, Dennis Brown, Jeffrey Bacha, Neil Sankar, Sarath Kanekal, Mark Leggas, Lars Wagner. A pilot pharmacokinetic study of VAL413 in patients with recurrent pediatric solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT137.