ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
A Phase I Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Combination Therapy with Refametinib plus Sorafenib in Patients with Advanced Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00785226 (A Phase 1/2 Study of the Combination of RDEA119 and Sorafenib in Patients With Advanced Cancer), which is not on this map. Cited by 15 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.
A Phase 1/2 Study of the Combination of RDEA119 and Sorafenib in Patients With Advanced Cancer
Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- A Phase I Study of Dinaciclib in Combination With MK-2206 in Patients With Advanced Pancreatic Cancer.Clinical and translational science · 2020Trial
- Prevalence of gastrointestinal side effects in hepatocellular carcinoma patients receiving sorafenib: a meta-analysis of 136 studies and 14,416 patients.Therapeutic advances in medical oncology · 2026Article
- Thiostrepton Suppresses the Progression of Rhabdomyosarcoma by Inhibiting the PI3K-AKT Signaling Pathway.Pediatric discovery · 2025Article
- Comprehensive bioinformatics analysis of omics data to reveal molecular mechanisms and biomarkers in multiple cancers.In silico pharmacology · 2025Article
- Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer.Biomedicines · 2024Review
- Transglutaminases are oncogenic biomarkers in human cancers and therapeutic targeting of TGM2 blocks chemoresistance and macrophage infiltration in pancreatic cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Review
- Targeting the PI3K and MAPK pathways to improve response to HER2-targeted therapies in HER2-positive gastric cancer.Journal of translational medicine · 2021Article
- A Phase I Trial of Trametinib in Combination with Sorafenib in Patients with Advanced Hepatocellular Cancer.The oncologist · 2020Article
- Article
- The MEK inhibitors enhance the efficacy of sorafenib against hepatocellular carcinoma cells through reducing p-ERK rebound.Translational cancer research · 2019Article
- Clinical Pharmacokinetics and Pharmacodynamics of Transarterial Chemoembolization and Targeted Therapies in Hepatocellular Carcinoma.Clinical pharmacokinetics · 2019Review
- Pharmacology of Pimasertib, A Selective MEK1/2 Inhibitor.European journal of drug metabolism and pharmacokinetics · 2018Review
- Article
- Comprehensive Analysis of miRNome Alterations in Response to Sorafenib Treatment in Colorectal Cancer Cells.International journal of molecular sciences · 2016Article
Corrections and comments
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Authors and funding
20 authors at 11 institutions in 5 countries.
Funding
Abstract
purposeTo assess the safety and tolerability of the small-molecule allosteric MEK inhibitor refametinib combined with sorafenib, in patients with advanced solid malignancies. EXPERIMENTAL
designThis phase I dose-escalation study included an expansion phase at the maximum tolerated dose (MTD). Patients received refametinib/sorafenib twice daily for 28 days, from a dose of refametinib 5 mg plus sorafenib 200 mg to a dose of refametinib 50 mg plus sorafenib 400 mg. Plasma levels of refametinib, refametinib metabolite M17, and sorafenib were measured for pharmacokinetic assessments. Tumors were biopsied at the MTD for analysis of MEK pathway mutations and ERK phosphorylation.
resultsThirty-two patients were enrolled in the dose-escalation cohort. The MTD was refametinib 50 mg twice daily plus sorafenib 400 mg twice daily. The most common treatment-related toxicities were diarrhea and fatigue. Refametinib was readily absorbed following oral administration (plasma half-life of ∼16 hours at the MTD), and pharmacokinetic parameters displayed near-dose proportionality, with less than 2-fold accumulation after multiple dosing. Another 30 patients were enrolled in the MTD cohort; 19 had hepatocellular carcinoma. The combination was associated with significantly reduced ERK phosphorylation in 5 out of 6 patients biopsied, with the greatest reductions in those with KRAS or BRAF mutations. Disease was stabilized in approximately half of patients, and 1 patient with colorectal cancer achieved a partial response at the MTD lasting approximately 1 year.
conclusionsIn this phase I study, refametinib plus sorafenib was well tolerated, with good oral absorption, near-dose proportionality, and target inhibition in a range of tumor types. Clin Cancer Res; 22(10); 2368-76. ©2015 AACR.
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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.