Trial reportJournal of neuro-oncology2012
A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression.
Trial report in Journal of neuro-oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Incorporation of biomarkers in phase II studies of recurrent glioblastoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Pooled it
- The role of targeted therapies in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline.Journal of neuro-oncology · 2014Guideline
- New Class of Benzodiazepinone Derivatives as Pro-Death Agents Targeting BIR Domains in Cancer Cells.Molecules (Basel, Switzerland) · 2023Article
- Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma.Frontiers in molecular neuroscience · 2022Review
- Bacterial terpenome.Natural product reports · 2021Review
- A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials.Cancers · 2021Review
- Kiaa0101 serves as a prognostic marker and promotes invasion by regulating p38/snail1 pathway in glioma.Annals of translational medicine · 2021Article
- Conceptual Evolution of Cell Signaling.International journal of molecular sciences · 2019Review
- Uncovering the potential of novel micromonosporae isolated from an extreme hyper-arid Atacama Desert soil.Scientific reports · 2019Article
- Complete Genome of Micromonospora sp. Strain B006 Reveals Biosynthetic Potential of a Lake Michigan Actinomycete.Journal of natural products · 2018Article
- Glioblastoma: new therapeutic strategies to address cellular and genomic complexity.Oncotarget · 2018Review
- Salvianolic acid B suppresses cell proliferation and induces apoptosis in osteosarcoma through p38-mediated reactive oxygen species generation.Oncology letters · 2018Article
- Galectin-1 is a poor prognostic factor in patients with glioblastoma multiforme after radiotherapy.BMC cancer · 2018Article
- New natural products identified by combined genomics-metabolomics profiling of marine Streptomyces sp. MP131-18.Scientific reports · 2017Article
- Targeting KRAS-mutant non-small cell lung cancer: challenges and opportunities.Acta biochimica et biophysica Sinica · 2016Review
- Targeted therapy in gliomas.Current oncology reports · 2014Review
- Targeting oncogenic ALK and MET: a promising therapeutic strategy for glioblastoma.Metabolic brain disease · 2013Review
- Radiation-induced upregulation of telomerase activity escapes PI3-kinase inhibition in two malignant glioma cell lines.International journal of oncology · 2013Article
- Targeting mutant KRAS for anticancer therapeutics: a review of novel small molecule modulators.Journal of medicinal chemistry · 2013Review
- Pathway-based personalized analysis of cancer.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This phase II trial was undertaken to evaluate the efficacy of TLN-4601 in patients with glioblastoma (GBM) at first progression. TLN-4601 inhibits the Ras-MAPK signaling pathway, and in animal models crosses the blood-brain barrier and accumulates in implanted gliomas, possibly by binding specifically to the peripheral benzodiazepine receptor. A maximum of 40 patients with recurrent GBM were to be enrolled in this study. TLN-4601 was administered at a dose of 480 mg/m(2)/day by continuous intravenous (CIV) administration. Each 21-day cycle consisted of a 14-day CIV administration and a 7-day recovery period. Samples were obtained from all patients for pharmacokinetic evaluations (PK) and for Raf-1 and pERK biomarker assessment using immunohistochemistry and flow cytometry. Following enrollment of 20 patients, this study was terminated due to a lack of efficacy. Of 17 evaluable patients, 14 had MR scans performed after two cycles of TLN-4601. Of these 14 patients, three had stable disease and 11 had disease progression. Only three patients had MR scans performed after four cycles and all had evidence of radiographic progression. Serum PKs confirmed that patients were exposed to TLN-4601 at targeted drug levels. TLN-4601 was generally well tolerated although two patients discontinued treatment due to adverse events. Biomarker analysis did not show consistent changes. TLN-4601 infused via CIV at 480 mg/m(2)/day for 14 of 21 days is well tolerated by patients with progressive GBM. However, this agent is ineffective in progressive GBM when administered as monotherapy in this schedule.
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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.