Evidence map›Paper›PMID 38015376›Full record

Trial reportJournal of neuro-oncology2023

A multi-site phase I trial of Veliparib with standard radiation and temozolomide in patients with newly diagnosed glioblastoma multiforme (GBM).

Lawrence Kleinberg, Xiaobu Ye, Jeff Supko, Glen H J Stevens, Hui-Kuo Shu, Tom Mikkelsen, Frank Lieberman, Glenn J Lesser, Emerson Lee, Stuart A Grossman

Abstract readClinical Trial, Phase IIClinical Trial, Phase I
PubMed Publisher
In one paragraph

Trial report in Journal of neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.1field-weighted citation impact, top 11% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 1 country.

Lawrence KleinbergRadiation Oncology and Radiation Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA. Kleinla@JHMI.edu.
Xiaobu YeNeurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Jeff SupkoMedicine, Harvard medical School, Boston, MA, USA.
Glen H J StevensNeurology, Cleveland Clinic, Cleveland, OH, USA.
Hui-Kuo ShuRadiation Oncology, Emory University, Atlanta, Georgia.
Tom MikkelsenJeffries Precision Medicine Center, Henry Ford Health, Detroit, MI, USA.
Frank LiebermanNeurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Glenn J LesserDepartment of Internal Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Emerson LeeRadiation Oncology and Radiation Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Stuart A GrossmanRadiation Oncology and Radiation Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Johns Hopkins Medicine · USCleveland Clinic · USEmory University · USHarvard University · USJohns Hopkins University · USUniversity of Pittsburgh · USWake Forest University · US

Funding

Adult Brain Tumor Consortium (ABTC)UM1CA137443 · NCI · JOHNS HOPKINS UNIVERSITY · PI GROSSMAN, STUART A · 2014 to 2020
$9.7M
NCI NIH HHS UM1 CA137443NIH HHS UM1 CA 137443
6 · The paper itself

Abstract

purposeA multi-site Phase I trial was conducted to determine the safety, maximum tolerated dose, and pharmacokinetics (PK) of Veliparib, a Poly (ADP-ribose) polymerase [PARP] enzyme inhibitor, when administered with temozolomide (TMZ) alone and then with temozolomide and radiation (RT) in patients with newly diagnosed glioblastoma.

methodsGiven the potential for myelosuppression when a PARP inhibitor is combined with chemotherapy, the first 6 patients accrued were given Veliparib 10 mg bid and TMZ 75 mg/m2/d daily for six weeks. If this was well tolerated, the same doses of Veliparib and TMZ would be tested along with standard radiation with plans to dose escalate the Veliparib in subsequent patient cohorts. Once a maximal tolerated dose was determined, a 78 patient phase II study was planned. Peripheral blood pharmacokinetics were assessed.

resultsTwenty-four patients were enrolled. In the first 6 patients who received 6 weeks of TMZ with Veliparib only one dose limiting toxicity (DLT) occurred. The next 12 patients received 6 weeks of RT + TMZ + veliparib and 4/12 (33%) had dose limiting hematologic toxicities. As a result, Veliparib was reduced by 50% to 10 mg BID every other week, but again 3/3 patients had dose limiting hematologic toxicities. The trial was then terminated. The mean clearance (± SD) CL/F of Veliparib for the initial dose (27.0 ± 9.0 L/h, n = 16) and at steady-state for 10 mg BID (23.5 ± 10.4 L/h, n = 18) were similar. Accumulation for BID dosing was 56% (± 33%).

conclusionsAlthough Veliparib 10 mg BID administered with TMZ 75 mg/m2 for six weeks was well tolerated, when this regimen was combined with standard partial brain irradiation it was severely myelosuppressive even when the dose was reduced by 50%. This study again highlights the potential of localized cranial radiotherapy to significantly increase hematologic toxicity of marginally myelosuppressive systemic therapies.

Indexed as

Antineoplastic AgentsBrain NeoplasmsGlioblastomaAntineoplastic Combined Chemotherapy ProtocolsBenzimidazolesHumansTemozolomideAntineoplastic AgentsBenzimidazolesTemozolomideveliparibGlioblastomaMyellosuppressionPARP inhibitorRadiotherapTemozolomideToxicity

Identifiers

PMID38015376
OpenAlexW4389085100

What OpenQuestion holds

Textmetadata
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.