ArticleBritish journal of cancer2015
A phase I trial of vertical inhibition of IGF signalling using cixutumumab, an anti-IGF-1R antibody, and selumetinib, an MEK 1/2 inhibitor, in advanced solid tumours.
Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- The Effect of Diabetes Mellitus on Lung Cancer Prognosis: A PRISMA-compliant Meta-analysis of Cohort Studies.Medicine · 2016Pooled it
- Randomized Phase II Trial of Capecitabine and Lapatinib with or without IMC-A12 (Cituxumumab) in Patients with HER2-Positive Advanced Breast Cancer Previously Treated with Trastuzumab and Chemotherapy: NCCTG N0733 (Alliance).Breast cancer research and treatment · 2021Trial
- A Phase I Study of Dinaciclib in Combination With MK-2206 in Patients With Advanced Pancreatic Cancer.Clinical and translational science · 2020Trial
- Population Pharmacokinetics of Selumetinib and Its Metabolite N-desmethyl-selumetinib in Adult Patients With Advanced Solid Tumors and Children With Low-Grade Gliomas.CPT: pharmacometrics & systems pharmacology · 2017Trial
- Postmarketing Safety Concerns of Teprotumumab: A Real-World Pharmacovigilance Assessment.The Journal of clinical endocrinology and metabolism · 2024Article
- Preclinical Therapeutic Efficacy of RAF/MEK/ERK and IGF1R/AKT/mTOR Inhibition in Neuroblastoma.Cancers · 2024Article
- Selumetinib: a selective MEK1 inhibitor for solid tumor treatment.Clinical and experimental medicine · 2023Review
- The Insulin-like Growth Factor System and Colorectal Cancer.Life (Basel, Switzerland) · 2022Review
- Article
- Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Clinical Pharmacokinetics and Pharmacodynamics of Selumetinib.Clinical pharmacokinetics · 2021Review
- Activation of the IGF Axis in Thyroid Cancer: Implications for Tumorigenesis and Treatment.International journal of molecular sciences · 2019Review
- Article
- A multitargeted probe-based strategy to identify signaling vulnerabilities in cancers.The Journal of biological chemistry · 2019Article
- Picropodophyllin (PPP) is a potent rhabdomyosarcoma growth inhibitor both in vitro and in vivo.BMC cancer · 2017Article
- Snail-Modulated MicroRNA 493 Forms a Negative Feedback Loop with the Insulin-Like Growth Factor 1 Receptor Pathway and Blocks Tumorigenesis.Molecular and cellular biology · 2017Article
- Molecular Checkpoint Decisions Made by Subverted Vascular Niche Transform Indolent Tumor Cells into Chemoresistant Cancer Stem Cells.Cancer cell · 2017Article
- Type I insulin-like growth factor receptor signaling in hematological malignancies.Oncotarget · 2017Review
- Novel therapeutics in metastatic colorectal cancer: molecular insights and pharmacogenomic implications.Expert review of clinical pharmacology · 2016Review
- IGF-binding protein 2 is a candidate target of therapeutic potential in cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundWe completed a phase I clinical trial to test the safety and toxicity of combined treatment with cixutumumab (anti-IGF-1R antibody) and selumetinib (MEK 1/2 inhibitor).
methodsPatients with advanced solid tumours, refractory to standard therapy received selumetinib hydrogen sulphate capsules orally twice daily, and cixutumumab intravenously on days 1 and 15 of each 28-day cycle. The study used a 3+3 design, with a dose-finding cohort followed by an expansion cohort at the maximally tolerated dose that included pharmacokinetic and pharmacodynamic correlative studies.
resultsThirty patients were enrolled, with 16 in the dose-finding cohort and 14 in the expansion cohort. Grade 3 or greater toxicities included nausea and vomiting, anaemia, CVA, hypertension, hyperglycaemia, and ophthalmic symptoms. The maximally tolerated combination dose was 50 mg twice daily of selumetinib and 12 mg kg(-1) every 2 weeks of cixutumumab. Two patients achieved a partial response (one unconfirmed), including a patient with BRAF wild-type thyroid carcinoma, and a patient with squamous cell carcinoma of the tongue, and six patients achieved time to progression of >6 months, including patients with thyroid carcinoma, colorectal carcinoma, and basal cell carcinoma. Comparison of pre- and on-treatment biopsies showed significant suppression of pERK and pS6 activity with treatment.
conclusionsOur study of anti-IGF-1R antibody cixutumumab and MEK 1/2 inhibitor selumetinib showed that the combination is safe and well-tolerated at these doses, with preliminary evidence of clinical benefit and pharmacodynamic evidence of target inhibition.
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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.