A phase I/II study of veliparib (ABT-888) with radiation and temozolomide in newly diagnosed diffuse pontine glioma: A Pediatric Brain Tumor Consortium study Journal Article


Authors: Baxter, P. A.; Su, J. M.; Onar-Thomas, A.; Billups, C. A.; Li, X. N.; Poussaint, T. Y.; Smith, E. R.; Thompson, P.; Adesina, A.; Ansell, P.; Giranda, V.; Paulino, A.; Kilburn, L.; Quaddoumi, I.; Broniscer, A.; Blaney, S. M.; Dunkel, I. J.; Fouladi, M.
Article Title: A phase I/II study of veliparib (ABT-888) with radiation and temozolomide in newly diagnosed diffuse pontine glioma: A Pediatric Brain Tumor Consortium study
Abstract: BACKGROUND: A Pediatric Brain Tumor Consortium (PBTC) phase I/II trial of veliparib and radiation followed by veliparib and temozolomide (TMZ) was conducted in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). The objectives were to: (i) estimate the recommended phase II dose (RP2D) of veliparib with concurrent radiation; (ii) evaluate the pharmacokinetic parameters of veliparib during radiation; (iii) evaluate feasibility of intrapatient TMZ dose escalation; (iv) describe toxicities of protocol therapy; and (v) estimate the overall survival distribution compared with historical series. METHODS: Veliparib was given Monday through Friday b.i.d. during radiation followed by a 4-week rest. Patients then received veliparib at 25 mg/m2 b.i.d. and TMZ 135 mg/m2 daily for 5 days every 28 days. Intrapatient dose escalation of TMZ was investigated for patients experiencing minimal toxicity. RESULTS: Sixty-six patients (65 eligible) were enrolled. The RP2D of veliparib was 65 mg/m2 b.i.d. with radiation. Dose-limiting toxicities during radiation with veliparib therapy included: grade 2 intratumoral hemorrhage (n = 1), grade 3 maculopapular rash (n = 2), and grade 3 nervous system disorder (generalized neurologic deterioration) (n = 1). Intrapatient TMZ dose escalation during maintenance was not tolerated. Following a planned interim analysis, it was concluded that this treatment did not show a survival benefit compared with PBTC historical controls, and accrual was stopped for futility. The 1- and 2-year overall survival rates were 37.2% (SE 7%) and 5.3% (SE 3%), respectively. CONCLUSION: Addition of veliparib to radiation followed by TMZ and veliparib was tolerated but did not improve survival for patients with newly diagnosed DIPG. TRIAL REGISTRATION: NCT01514201. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Keywords: cns tumors; veliparib; dipg; abt-888; parp inhibition
Journal Title: Neuro-Oncology
Volume: 22
Issue: 6
ISSN: 1522-8517
Publisher: Oxford University Press  
Date Published: 2020-06-01
Start Page: 875
End Page: 885
Language: English
DOI: 10.1093/neuonc/noaa016
PUBMED: 32009149
PROVIDER: scopus
PMCID: PMC7283021
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Ira J Dunkel
    333 Dunkel