Evidence map›Paper›PMID 32598442›Full record

ArticleNeuro-oncology2020

Phase 0 and window of opportunity clinical trial design in neuro-oncology: a RANO review.

Michael A Vogelbaum, Daria Krivosheya, Hamid Borghei-Razavi, Nader Sanai, Michael Weller, Wolfgang Wick, Riccardo Soffietti, David A Reardon, Manish K Aghi, Evanthia Galanis and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
–field-weighted citation impact
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

50 citing papers in PubMed.

  1. A Phase 0 Trial of Ceritinib in Patients with Brain Metastases and Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
  2. Accelerating discovery: Transformative clinical trial models in neuro-oncology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
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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

13 authors.

Michael A VogelbaumNeuroOncology Program, Moffitt Cancer Center, Tampa, Florida, USA.
Daria KrivosheyaDepartment of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA.
Hamid Borghei-RazaviDepartment of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA.
Nader SanaiIvy Brain Tumor Center, Barrow Neurological Institute, Phoenix, Arizona, USA.
Michael WellerDepartment of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
Wolfgang WickDepartment of Neurology Heidelberg University Hospital and German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany.
Riccardo SoffiettiDepartment of Neuro-Oncology, University and City of Health and Science, Turin, Italy.
David A ReardonCenter For Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, Massachusetts, USA.
Manish K AghiDepartment of Neurosurgery, University of California San Francisco, San Francisco, California, USA.
Evanthia GalanisDepartment of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Patrick Y WenCenter For Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, Massachusetts, USA.
Martin van den BentThe Brain Tumor Center at Erasmus MC Cancer Institute, University Medical Center Rotterdam.
Susan ChangDepartment of Neurosurgery, University of California San Francisco, San Francisco, California, USA.

Funding

Tumor cell and microenvironment changes causing antiangiogenic therapy resistanceR01NS079697 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AGHI, MANISH · 2013 to 2021
$3.2M
Modeling and druggable-genome screening of glioblastoma invasion using regional biopsy-guided biomaterials systemsR01CA227136 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AGHI, MANISH · 2018 to 2022
$2.2M
NCI NIH HHS R01 CA227136NINDS NIH HHS R01 NS079697
6 · The paper itself

Abstract

Glioblastoma is a devastating disease with poor prognosis. Few effective chemotherapeutics are currently available, and much effort has been expended to identify new drugs capable of slowing tumor progression. The phase 0 trial design was developed to facilitate early identification of promising agents for cancer that should undergo accelerated approval. This design features an early in-human study that enrolls a small number of patients who receive subtherapeutic doses of medication with the goals of describing pharmacokinetics through drug blood level measurements and determining intratumoral concentrations of the investigational compound as well as pharmacodynamics by studying the biochemical and physiological effects of drugs. In neuro-oncology, however, the presence of the blood-brain barrier and difficulty in obtaining brain tumor tissue warrant a separate set of considerations. In this paper, we critically reviewed the protocols used in all brain tumor related in-human phase 0 and phase 0-like ("window of opportunity") studies between 1993 and 2018, as well as ongoing clinical trials, and identified major challenges in trial design as applied to central nervous system tumors that include surgical specimen collection and storage, brain tumor drug level analysis, and confirmation of drug action. We therefore propose that phase 0 trials in neuro-oncology should include (i) only patients in whom a resection of the tumor is planned, (ii) use of clinical doses of an investigational agent, (iii) tissue sampling from enhancing and non-enhancing portions of the tumor, and (iv) assessment of drug-specific target effects. Standardization of clinical protocols for phase 0/window of opportunity studies can help accelerate the development of effective treatments for glioblastoma.

Indexed as

Central Nervous System NeoplasmsGlioblastomaClinical Trials as TopicHumansTreatment Outcomeclinical trialglioblastomapharmacodynamicspharmacokineticsphase 0

Identifiers

PMID32598442
PMCPMC7690357

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.