ArticlePediatric blood & cancer2014
A phase I trial of MK-2206 in children with refractory malignancies: a Children's Oncology Group study.
Article in Pediatric blood & cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update.Cancer medicine · 2017Pooled it
- Novel pharmacodynamic biomarkers for MYCN protein and PI3K/AKT/mTOR pathway signaling in children with neuroblastoma.Molecular oncology · 2016Trial
- Results of an abbreviated phase-II study with the Akt Inhibitor MK-2206 in Patients with Advanced Biliary Cancer.Scientific reports · 2015Trial
- Pediatric Cancer Models in Zebrafish.Trends in cancer · 2020Review
- Deep graph embedding for prioritizing synergistic anticancer drug combinations.Computational and structural biotechnology journal · 2020Article
- Selective Targeting of Myoblast Fusogenic Signaling and Differentiation-Arrest Antagonizes Rhabdomyosarcoma Cells.Cancer research · 2019Article
- The FDA NIH Biomarkers, EndpointS, and other Tools (BEST) resource in neuro-oncology.Neuro-oncology · 2018Review
- AKT1 restricts the invasive capacity of head and neck carcinoma cells harboring a constitutively active PI3 kinase activity.BMC cancer · 2018Article
- Early phase clinical trials of anticancer agents in children and adolescents - an ITCC perspective.Nature reviews. Clinical oncology · 2017Review
- Maximising the potential of AKT inhibitors as anti-cancer treatments.Pharmacology & therapeutics · 2017Review
- Review
- A phase I study of single-agent perifosine for recurrent or refractory pediatric CNS and solid tumors.PloS one · 2017Article
- Novel B55α-PP2A mutations in AML promote AKT T308 phosphorylation and sensitivity to AKT inhibitor-induced growth arrest.Oncotarget · 2016Article
- Cell Proliferation in Neuroblastoma.Cancers · 2016Review
- Phase I trial of weekly MK-0752 in children with refractory central nervous system malignancies: a pediatric brain tumor consortium study.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2015Article
- Molecular biology of pediatric brain tumors and impact on novel therapies.Current neurology and neuroscience reports · 2015Review
- Triple Akt inhibition as a new therapeutic strategy in T-cell acute lymphoblastic leukemia.Oncotarget · 2015Article
- PDK1-mTOR signaling pathway inhibitors reduce cell proliferation in MK2206 resistant neuroblastoma cells.Cancer cell international · 2015Article
- Management of diffuse intrinsic pontine glioma in children: current and future strategies for improving prognosis.CNS oncology · 2014Review
- Improving the outcome for children with cancer: Development of targeted new agents.CA: a cancer journal for cliniciansReview
Corrections and comments
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Authors and funding
13 authors at 9 institutions in 2 countries.
Funding
Abstract
backgroundWe report results of a phase I trial designed to estimate the maximum tolerated dose (MTD), describe dose-limiting toxicities (DLT), and characterize the pharmacokinetic profile of MK-2206, an AKT inhibitor, in children with refractory or recurrent malignancies. PROCEDURE: MK-2206 was administered either every other day (Schedule 1), or once a week (Schedule 2) in a 28-day cycle. Dose escalations in increments of ∼30% were independently made in each part using the rolling-six design. Serial pharmacokinetic (PK) studies were obtained. Biological studies include analysis of PI3K/PTEN/AKT-cell signaling pathway in pre and post-therapy in PBMC and in tumors at diagnosis or recurrence.
resultsFifty patients (26 males, median age 12.6 years [range, 3.1-21.9]) with malignant glioma (16), ependymoma (4), hepatocellular carcinoma (3), gliomatosis cereberi (2), or other tumors (22) were enrolled; 40 were fully evaluable for toxicity (Schedule 1, n = 23; Schedule 2, n = 17). Schedule 1 DLTs included: grade 3 dehydration in 1/6 patients at 28 mg/m(2) ; grade 4 hyperglycemia and neutropenia in 1/6 patients at 45 mg/m(2) ; and grade 3 rash in 3/6 patients at dose level 4 (58 mg/m(2) ). Schedule 2 DLTs included: grade 3 alkaline phosphatase in 1/6 patients at 90 mg/m(2) ; grade 3 rash in 1/6 patients at 120 mg/m(2) ; and grade 3 rash in 2/6 patients at 155 mg/m(2) .
conclusionsThe recommended pediatric phase 2 dose of MK-2206 is 45 mg/m(2) /dose every other day or 120 mg/m(2) /dose weekly. PK appeared linear over the dose range studied.
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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.