Evidence map›Paper›PMID 27252174›Full record

ArticleScience translational medicine2016

Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma.

Timothy F Cloughesy, Joseph Landolfi, Daniel J Hogan, Stephen Bloomfield, Bob Carter, Clark C Chen, J Bradley Elder, Steven N Kalkanis, Santosh Kesari, Albert Lai and 20 more

Registry-linked trialAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02414165 (A Phase 2/3 Randomized, Open-Label Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC Versus Standard of Care in Subjects Undergoing Planned Resection for Recurrent Glioblastoma or Anaplastic Astrocytoma), which is not on this map. Cited by 117 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 2 pooled it
15.3field-weighted citation impact, top 1% 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.

NCT02414165 phase2 / phase3terminatednot on this map

A Phase 2/3 Randomized, Open-Label Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC Versus Standard of Care in Subjects Undergoing Planned Resection for Recurrent Glioblastoma or Anaplastic Astrocytoma

TypeinterventionalSponsorTocagen Inc.Ran2015 to 2019Enrolled403ConditionsGlioblastoma Multiforme, Anaplastic AstrocytomaArmsToca 511, Toca FC, Lomustine, Temozolomide, Bevacizumab
3 · Its place in the literature

Who cites it

117 citing papers in PubMed, 2 syntheses or guidelines pooled it, 197 citations in OpenAlex.

  1. Pooled it
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  3. Trial
  4. Trial
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  6. Oncolytic H-1 Parvovirus Shows Safety and Signs of Immunogenic Activity in a First Phase I/IIa Glioblastoma Trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2017
    Trial
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Co-evolution of glioma and immune microenvironment.Journal for immunotherapy of cancer · 2024
    Review
  13. Review
  14. Review
  15. Review
  16. Current approaches in glioblastoma multiforme immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Review
  17. Review
  18. Article
  19. Article
  20. Article

57 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 3 institutions in 1 country.

Timothy F CloughesyDepartment of Neuro-Oncology and Department of Neurosurgery, 710 Westwood Plaza, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Joseph LandolfiNew Jersey Neuroscience Institute, John F. Kennedy Medical Center, 65 James Street, Edison, NJ 08820, USA.
Daniel J HoganTocagen Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA.
Stephen BloomfieldNew Jersey Neuroscience Institute, John F. Kennedy Medical Center, 65 James Street, Edison, NJ 08820, USA.
Bob CarterMoores Cancer Center, Department of Neurosciences, University of California, San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093, USA.
Clark C ChenMoores Cancer Center, Department of Neurosciences, University of California, San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093, USA.
J Bradley ElderOhio State University Wexner Medical Center, 410 West 10th Avenue, Columbus, OH 43210, USA.
Steven N KalkanisHenry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Santosh KesariMoores Cancer Center, Department of Neurosciences, University of California, San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093, USA.
Albert LaiDepartment of Neuro-Oncology and Department of Neurosurgery, 710 Westwood Plaza, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Ian Y LeeHenry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Linda M LiauDepartment of Neuro-Oncology and Department of Neurosurgery, 710 Westwood Plaza, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Tom MikkelsenHenry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Phioanh Leia NghiemphuDepartment of Neuro-Oncology and Department of Neurosurgery, 710 Westwood Plaza, University of California, Los Angeles, Los Angeles, CA 90095, USA.
David PiccioniMoores Cancer Center, Department of Neurosciences, University of California, San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093, USA.
Tobias WalbertHenry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Alice ChuTocagen Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA.
Asha DasTocagen Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA.
Oscar R DiagoTocagen Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA.
Dawn GammonTocagen Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA.
Harry E GruberTocagen Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA.
Michelle HannaRibomed Biotechnologies Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA. University of Arizona Cancer Center, 1515 North Campbell Avenue, Tucson, AZ 85724, USA.
Douglas J JollyTocagen Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA.
Noriyuki KasaharaDepartment of Cell Biology and Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
David McCarthyRibomed Biotechnologies Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA.
Leah MitchellTocagen Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA.
Derek OstertagTocagen Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA.
Joan M RobbinsTocagen Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA.
Maria Rodriguez-AguirreTocagen Inc., 3030 Bunker Hill Street, San Diego, CA 92109, USA.
Michael A VogelbaumCleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. vogelbm@ccf.org.
Henry Ford Hospital · USCleveland Clinic · USUniversity of Arizona Cancer Center

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Translational Development of Replication-Competent Retrovirus VectorsU01NS059821 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KASAHARA, NORIYUKI · 2010 to 2013
$2.9M
Targeting Mechanisms of Acquired Temozolomide Resistance in GlioblastomaR01NS097649 · NINDS · UNIVERSITY OF MINNESOTA · PI CHEN, CLARK CHIN-CHUNG · 2016 to 2021
$1.7M
NCI NIH HHS P30 CA016042NINDS NIH HHS R01 NS097649NINDS NIH HHS U01 NS059821
6 · The paper itself

Abstract

Toca 511 (vocimagene amiretrorepvec) is an investigational nonlytic, retroviral replicating vector (RRV) that delivers a yeast cytosine deaminase, which converts subsequently administered courses of the investigational prodrug Toca FC (extended-release 5-fluorocytosine) into the antimetabolite 5-fluorouracil. Forty-five subjects with recurrent or progressive high-grade glioma were treated. The end points of this phase 1, open-label, ascending dose, multicenter trial included safety, efficacy, and molecular profiling; survival was compared to a matching subgroup from an external control. Overall survival for recurrent high-grade glioma was 13.6 months (95% confidence interval, 10.8 to 20.0) and was statistically improved relative to an external control (hazard ratio, 0.45; P = 0.003). Tumor samples from subjects surviving more than 52 weeks after Toca 511 delivery disproportionately displayed a survival-related mRNA expression signature, identifying a potential molecular signature that may correlate with treatment-related survival rather than being prognostic. Toca 511 and Toca FC show excellent tolerability, with RRV persisting in the tumor and RRV control systemically. The favorable assessment of Toca 511 and Toca FC supports confirmation in a randomized phase 2/3 trial (NCT02414165).

Indexed as

Genetic VectorsGliomaRetroviridaeConfidence IntervalsCytosine DeaminaseFlucytosineFluorouracilHumansProdrugsRNA, MessengerCytosine DeaminaseFlucytosineFluorouracilProdrugsRNA, Messenger

Identifiers

PMID27252174
PMCPMC6707068
OpenAlexW2418524314

What OpenQuestion holds

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Read underepoch 390

Registered trials

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.