Evidence map›Paper›PMID 24908656›Full record

ArticleNeuro-oncology2014

A phase I trial of veliparib (ABT-888) and temozolomide in children with recurrent CNS tumors: a pediatric brain tumor consortium report.

Jack M Su, Patrick Thompson, Adekunle Adesina, Xiao-Nan Li, Lindsay Kilburn, Arzu Onar-Thomas, Mehmet Kocak, Brenda Chyla, Evelyn McKeegan, Katherine E Warren and 8 more

Open access · bronzeAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 2 pooled it
3.1field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.

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  16. The use of radiosensitizing agents in the therapy of glioblastoma multiforme-a comprehensive review.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 3 countries.

Jack M SuTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Patrick ThompsonTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Adekunle AdesinaTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Xiao-Nan LiTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Lindsay KilburnTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Arzu Onar-ThomasTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Mehmet KocakTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Brenda ChylaTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Evelyn McKeeganTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Katherine E WarrenTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Stewart GoldmanTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Ian F PollackTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Maryam FouladiTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Alice ChenTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Vincent GirandaTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
James BoyettTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Larry KunTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Susan M BlaneyTexas Children's Cancer Center, Baylor College of Medicine (J.M.S., P.T., A.A., X-N.L., S.M.B.); Children's National Medical Center (L.K.); St. Jude Children's Research Hospital (A.O-T., J.B., L.K.); University of Tennessee Health Science Center (M.K.); AbbVie Pharmaceuticals (B.C., E.M., V.G.); National Cancer Institute, Pediatric Oncology Branch (K.E.W.); Children's Hospital of Chicago (S.G.); Children's Hospital of Pittsburgh (I.F.P.); Cincinnati Children's Hospital Medical Center (M.F.); Cancer Therapy Evaluation Program, National Cancer Institute (A.C.).
Children's Cancer Center · USAbbVie (United States) · USNational Cancer Institute · MYBaylor College of Medicine · USSt. Jude Children's Research Hospital · USChildren's National · USUniversity of Tennessee Health Science Center · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
Pediatric Brain Tumor Consortium (PBTC)UM1CA081457 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Ira J Dunkel, Arzu Onar-Thomas · 2014 to 2026
$41.4M
The Pediatric Brain Tumor Consortium (PBTC)U01CA081457 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI BOYETT, JAMES MILFORD · 1999 to 2013
$29.2M
Early Clinical Trials for Children with CNS TumorsZIABC011447 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WARREN, KATHERINE E · 2012 to 2019
$2.1M
NCI NIH HHS P30 CA021765NCI NIH HHS U01 CA81457NCI NIH HHS UM1 CA081457
6 · The paper itself

Abstract

backgroundA phase I trial of veliparib (ABT-888), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, and temozolomide (TMZ) was conducted in children with recurrent brain tumors to (i) estimate the maximum tolerated doses (MTDs) or recommended phase II doses (RP2Ds) of veliparib and TMZ; (ii) describe the toxicities of this regimen; and (iii) evaluate the plasma pharmacokinetic parameters and extent of PARP inhibition in peripheral blood mononuclear cells (PBMCs) following veliparib.

methodsTMZ was given once daily and veliparib twice daily for 5 days every 28 days. Veliparib concentrations and poly(ADP-ribose) (PAR) levels in PBMCs were measured on days 1 and 4. Analysis of pharmacokinetic and PBMC PAR levels were performed twice during study conduct to rationally guide dose modifications and to determine biologically optimal MTD/RP2D.

resultsTwenty-nine evaluable patients were enrolled. Myelosuppression (grade 4 neutropenia and thrombocytopenia) were dose limiting. The RP2Ds are veliparib 25 mg/m(2) b.i.d. and TMZ 135 mg/m(2)/d. Only 2 out of 12 patients treated at RP2Ds experienced dose-limiting toxicities. Although no objective response was observed, 4 patients had stable disease >6 months in duration, including 1 with glioblastoma multiforme and 1 with ependymoma. At the RP2D of veliparib, pediatric pharmacokinetic parameters were similar to those in adults.

conclusionsVeliparib and TMZ at the RP2D were well tolerated in children with recurrent brain tumors. A phase I/II trial to evaluate the tolerability and efficacy of veliparib, TMZ, and radiation in children with newly diagnosed brainstem gliomas is in progress.

Indexed as

Poly(ADP-ribose) Polymerase InhibitorsAdolescentAdultAntineoplastic Agents, AlkylatingBenzimidazolesBrain NeoplasmsChildChild, PreschoolDacarbazineFemaleHumansInfantLeukocytes, MononuclearMaleMaximum Tolerated DosePoly(ADP-ribose) PolymerasesAntineoplastic Agents, AlkylatingBenzimidazolesDacarbazinePoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesTemozolomideveliparibABT-888CNS tumorsPARP inhibitionpediatric phase I studyveliparib

Identifiers

PMID24908656
PMCPMC4232081
OpenAlexW2035566238

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.