Evidence map›Paper›PMID 29313954›Full record

Trial reportCancer2018

Phase 1/2 trial of temsirolimus and sorafenib in the treatment of patients with recurrent glioblastoma: North Central Cancer Treatment Group Study/Alliance N0572.

David Schiff, Kurt A Jaeckle, S Keith Anderson, Evanthia Galanis, Caterina Giannini, Jan C Buckner, Phillip Stella, Patrick J Flynn, Bradley J Erickson, John F Schwerkoske and 5 more

Open access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 5 pooled it
4.4field-weighted citation impact, top 5% 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

37 citing papers in PubMed, 5 syntheses or guidelines pooled it, 58 citations in OpenAlex.

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  20. Therapeutic Options in Neuro-Oncology.International journal of molecular sciences · 2022
    Review
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

15 authors at 7 institutions in 2 countries.

David SchiffDivision of Neuro-Oncology, Neuro-Oncology Center, University of Virginia Health System, Charlottesville, Virginia.ORCID 0000-0002-1896-2502
Kurt A JaeckleAtlantic Health System, Summit, New Jersey.
S Keith AndersonAlliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota.
Evanthia GalanisDepartment of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
Caterina GianniniAlliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota.
Jan C BucknerDepartment of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
Phillip StellaMedical Oncology Program, St. Joseph Mercy Health System, Ann Arbor, Michigan.
Patrick J FlynnMetro Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota.
Bradley J EricksonDepartment of Radiology, Mayo Clinic, Rochester, Minnesota.
John F SchwerkoskeMinnesota Oncology, Woodbury, Minnesota.
Vesna KaluzaMedical Oncology Program, St. Joseph Mercy Health System, Ann Arbor, Michigan.
Erin TwohyAlliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota.
Janet DanceyCancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, Maryland.
John WrightCancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, Maryland.
Jann N SarkariaDepartment of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
Mayo Clinic · USMercy Health System · USNational Cancer Institute · MYAtlantic Health System · USComprehensive OBGYN · USMetro-Minnesota Community Oncology Research Consortium · USUniversity of Virginia Health System · US

Funding

Member Site CoreU10CA180821 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Evanthia Galanis · 2014 to 2026
$177.3M
Statistics CoreU10CA180882 · NCI · MAYO CLINIC ROCHESTER · PI Sumithra Jay Mandrekar · 2014 to 2026
$115.0M
TRANSLATIONAL RESEARCHU10CA025224 · NCI · MAYO CLINIC ROCHESTER · PI BUCKNER, JAN C · 1985 to 2013
$85.0M
Metro-Minnesota Community Oncology Research Consortium (MMCORC)UG1CA189863 · NCI · PARK NICOLLET INSTITUTE · PI JOLEEN M HUBBARD, Yan Ji · 2014 to 2026
$43.2M
NCI NIH HHS U10 CA025224NCI NIH HHS U10 CA180821NCI NIH HHS U10 CA180882NCI NIH HHS UG1 CA189863
6 · The paper itself

Abstract

backgroundMitogen-activated protein kinase (MAPK) activation and mammalian target of rapamycin (mTOR)-dependent signaling are hallmarks of glioblastoma. In the current study, the authors conducted a phase 1/2 study of sorafenib (an inhibitor of Raf kinase and vascular endothelial growth factor receptor 2 [VEGFR-2]) and the mTOR inhibitor temsirolimus in patients with recurrent glioblastoma.

methodsPatients with recurrent glioblastoma who developed disease progression after surgery or radiotherapy plus temozolomide and with ≤2 prior chemotherapy regimens were eligible. The phase 1 endpoint was the maximum tolerated dose (MTD), using a cohorts-of-3 design. The 2-stage phase 2 study included separate arms for VEGF inhibitor (VEGFi)-naive patients and patients who progressed after prior VEGFi.

resultsThe MTD was sorafenib at a dose of 200 mg twice daily and temsirolimus at a dose of 20 mg weekly. In the first 41 evaluable patients who were treated at the phase 2 dose, there were 7 who were free of disease progression at 6 months (progression-free survival at 6 months [PFS6]) in the VEGFi-naive group (17.1%); this finding met the prestudy threshold of success. In the prior VEGFi group, only 4 of the first 41 evaluable patients treated at the phase 2 dose achieved PFS6 (9.8%), and this did not meet the prestudy threshold for success. The median PFS for the 2 groups was 2.6 months and 1.9 months, respectively. The median overall survival for the 2 groups was 6.3 months and 3.9 months, respectively. At least 1 adverse event of grade ≥3 was observed in 75.5% of the VEGFi-naive patients and in 73.9% of the prior VEGFi patients.

conclusionsThe limited activity of sorafenib and temsirolimus at the dose and schedule used in the current study was observed with considerable toxicity of grade ≥3. Significant dose reductions that were required in this treatment combination compared with tolerated single-agent doses may have contributed to the lack of efficacy. Cancer 2018;124:1455-63. © 2018 American Cancer Society.

Indexed as

AdultAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsFemaleFollow-Up StudiesGlioblastomaHumansMaleMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalPrognosisSirolimusSorafenibSurvival RateSirolimusSorafenibtemsirolimusclinical trialglioblastomasorafenibtargeted therapytemsirolimus

Identifiers

PMID29313954
PMCPMC5867230
OpenAlexW2782514367

What OpenQuestion holds

Textmetadata
LicenceTDM
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.