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

Patricia A. Baxter*, Jack M. Su, Arzu Onar-Thomas, Catherine A. Billups, Xiao Nan Li, Tina Young Poussaint, Edward R. Smith, Patrick Thompson, Adekunle Adesina, Pete Ansell, Vincent Giranda, Arnold Paulino, Lindsey Kilburn, Ibrahim Quaddoumi, Alberto Broniscer, Susan M. Blaney, Ira J. Dunkel, Maryam Fouladi

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)875-885
Number of pages11
JournalNeuro-oncology
Volume22
Issue number6
DOIs
StatePublished - Jun 9 2020

Keywords

  • ABT-888
  • CNS tumors
  • DIPG
  • PARP inhibition
  • veliparib

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    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. (2020). 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. Neuro-oncology, 22(6), 875-885. https://doi.org/10.1093/neuonc/noaa016