ArticleBritish journal of cancer2013
A phase I study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (PJC-004/NCI 8503).
Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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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.
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Who cites it
49 citing papers in PubMed, 76 citations in OpenAlex.
- Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors.The New England journal of medicine · 2023Trial
- A phase II study of paclitaxel for the treatment of ovarian stromal tumors: An NRG Oncology/ Gynecologic Oncology Group Study.Gynecologic oncology · 2016Trial
- A randomized phase II study of cediranib alone versus cediranib in combination with dasatinib in docetaxel resistant, castration resistant prostate cancer patients.Investigational new drugs · 2014Trial
- A phase II study of the gamma secretase inhibitor RO4929097 in patients with previously treated metastatic pancreatic adenocarcinoma.Investigational new drugs · 2014Trial
- Targeting the Notch1-YY1-ICAM1 Signaling Axis Enhances the Efficacy of Immunotherapy in HCC by Activating CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Structural basis of human γ-secretase inhibition by anticancer clinical compounds.Nature structural & molecular biology · 2025Article
- Notch signaling in the tumor immune microenvironment of colorectal cancer: mechanisms and therapeutic opportunities.Journal of translational medicine · 2025Review
- Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.Frontiers of medicine · 2025Review
- Targeted Treatment against Cancer Stem Cells in Colorectal Cancer.International journal of molecular sciences · 2024Review
- Targeting the DLL/Notch Signaling Pathway in Cancer: Challenges and Advances in Clinical Development.Molecular cancer therapeutics · 2023Review
- The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics.International journal of biological sciences · 2023Review
- Signaling pathways in the regulation of cancer stem cells and associated targeted therapy.MedComm · 2022Review
- Prevalence of Tumours and Tumour-like Lesions in Domestic and Exotic Animals from Lower Silesia and its Surrounds in Poland in 2014-2017.Journal of veterinary research · 2022Article
- Phase I study of cediranib, an oral VEGFR inhibitor, in combination with selumetinib, an oral MEK inhibitor, in patients with advanced solid malignancies.Investigational new drugs · 2022Article
- Identification, Culture and Targeting of Cancer Stem Cells.Life (Basel, Switzerland) · 2022Review
- Review
- Gamma Secretase Inhibitors in Cancer: A Current Perspective on Clinical Performance.The oncologist · 2021Review
- Therapeutic Targeting of Notch Signaling: From Cancer to Inflammatory Disorders.Frontiers in cell and developmental biology · 2021Review
- A phase I study of an oral selective gamma secretase (GS) inhibitor RO4929097 in combination with neoadjuvant paclitaxel and carboplatin in triple negative breast cancer.Investigational new drugs · 2020Article
- Notch Transduction in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe Notch signalling pathway has been implicated in tumour initiation, progression, angiogenesis and development of resistance to vascular endothelial growth factor (VEGF) targeting, providing a rationale for the combination of RO4929097, a γ-secretase inhibitor, and cediranib, a VEGF receptor tyrosine kinase inhibitor.
methodsPatients received escalating doses of RO4929097 (on a 3 days-on and 4 days-off schedule) in combination with cediranib (once daily). Cycle 1 was 42 days long with RO4929097 given alone for the first 3 weeks followed by the co-administration of both RO4929097 and cediranib starting from day 22. Cycle 2 and onwards were 21 days long. Soluble markers of angiogenesis were measured in plasma samples. Archival tumour specimens were assessed for expression of three different components of Notch signalling pathway and genotyping.
resultsIn total, 20 patients were treated in three dose levels (DLs). The recommended phase II dose was defined as 20 mg for RO4929097 on 3 days-on and 4 days-off schedule and 30 mg daily for cediranib. The most frequent treatment-related adverse events (AEs) were diarrhoea, hypertension, fatigue and nausea. Eleven patients had a best response of stable disease and one patient achieved partial response. We did not detect any correlation between tested biomarkers of angiogenesis or the Notch pathway and treatment effect. There was no correlation between mutational status and time to treatment failure.
conclusionRO4929097 in combination with cediranib is generally well tolerated at the DLs tested. Preliminary evidence of antitumour efficacy with prolonged disease stabilisation in some patients with progressive malignancies warrants further clinical investigation of this treatment strategy.
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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.