An inhibitor of glycogen phosphorylase. Buy CP 316 819 CAS 186392-43-8, MF: C21H22ClN3O4, MW: 415.87 from Santa Cruz Biotechnolog High Purity & Great Value. Shop for Life Science Reagents for Lab Research Now! Trusted and Innovative Life Science Reagents - Cited in 30,000+ Citations BOSTON - The investigational MEK inhibitor selumetinib showed clinical responses in adult patients with neurofibromatosis type 1-associated plexiform neurofibromas, according to preliminary results from an ongoing phase II study presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Oct. 26-30
Phase II trial of the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886 Hydrogen Sulfate) in adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN). | Journal of Clinical Oncology Journal of Clinical Oncology > List of Issues > Volume 38, Issue 15_suppl > Selumetinib, a kinase inhibitor, is the first therapy approved for pediatric patients who have this debilitating, and often disfiguring, rare disease Selumetinib is a substrate of CYP3A4, BCRP, and P-gp transporters Antiplatelet antagonists or vitamin K antagonists Capsules contain vitamin E and daily intake of vitamin E that exceeds the.. Selumetinib (AZD6244 or ARRY-142886) is an oral selective inhibitor of MEK 1 and 2 that has shown activity against several advanced adult cancers. 28-30 We report here the results of a phase 1. Selumetinib in Treating Patients with Neurofibromatosis Type 1 and Cutaneous Neurofibroma This pilot phase II trial studies how well selumetinib works in treating patients with neurofibromatosis type 1 and cutaneous neurofibromas. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
Permanent selumetinib discontinuation due to left ventricular dysfunction or decreased LVEF also occurred in adults with multiple tumor types (selumetinib is not approved for use in adults). The safety of selumetinib has not been established in patients with a history of impaired LVEF or a baseline ejection fraction that is below the. TPS2596 Background: PNs in NF1 are a major source of morbidity, causing disfigurement, functional impairment, and pain. Selumetinib is an oral inhibitor of MEK 1/2, which may mediate anti-tumor effects in PNs by inhibiting Ras signaling. Selumetinib is currently undergoing evaluation in adult cancers, pediatric brain tumors and NF1 related PNs. Our phase I trial of selumetinib for children. KOSELUGO ® (selumetinib) is the FIRST and ONLY FDA-approved prescription medicine that is used to treat children 2 years of age and older with neurofibromatosis type 1 (NF1) who have plexiform neurofibromas that cannot be completely removed by surgery. It is not known if Koselugo is safe and effective in children under 2 years of age Selumetinib is a kinase inhibitor, more specifically a selective inhibitor of the enzyme mitogen-activated protein kinase kinase (MAPK kinase or MEK) subtypes 1 and 2. These enzymes are part of the MAPK/ERK pathway, which regulates cell proliferation (i.e., growth and division) and is overly active in many types of cancer
Evaluate the confirmed partial and complete response rate of selumetinib in children and young adults with NF1 and inoperable PN [Time Frame: prior to cycles 5, 6, 13, 17, 21, 25 and then every 6 cycles] Secondary Outcomes Determine effect on growth rate of PN [Time Frame: At time of PD The U.S. Food and Drug Administration (FDA) approved Koselugo (selumetinib) for use in patients with inoperable plexiform neurofibromas, a common manifestation in the disease neurofibromatosis type one (NF1)
Absorption. Based on several studies investigating selumetinib at various doses in both pediatric and adult populations, the Tmax generally ranges between 1- 1.5 hours. 1,2,13 In healthy adults, the mean absolute oral bioavailability was reported to be 62%. 13 Selumetinib should be administered on an empty stomach since food significantly decreases serum concentrations of the drug. 1 Methods: Pediatric and adult patients with NF1 and inoperable PN participating in phase 2 studies of selumetinib for PN were included in this analysis if they had SNF and serial spine magnetic resonance imaging (MRI). Selumetinib was administered orally at the recommended dose of 25 mg/m 2 /dose twice daily (max 50 mg b.i.d.; 1 cycle = 28 days.
TPS2596. Background: PNs in NF1 are a major source of morbidity, causing disfigurement, functional impairment, and pain. Selumetinib is an oral inhibitor of MEK 1/2, which may mediate anti-tumor effects in PNs by inhibiting Ras signaling. Selumetinib is currently undergoing evaluation in adult cancers, pediatric brain tumors and NF1 related PNs safety data in adults. Conclusion: This study showed that selumetinib is a clinically beneficial treatment for patients between the ages of 2 to 18 with progressive NF1 and inoperable PN
Selumetinib has been evaluated for many adult and pedi-atric solid tumors or hematological malignancies as a single agent,4-12 in combination with cytotoxics,13-16 or other tar-geted therapeutic agents.17 The initial formulation taken into adult phase I trials was a free-base oral suspension Selumetinib was a minor component in urine, accounting for ≤1% of the dose. M2 was the most abundant metabolite in urine, accounting for 10% of the dose, and there were 5 other metabolites accounting for between 1% and 10% of the dose. In feces, selumetinib accounted for a mean of 19% of the dose Koselugo (selumetinib) is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2). MEK1/2 prote ins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. Both MEK and ERK are critical components of the RAS-regulated RAF-MEK -ERK pathway, which is often activated in different types of cancers Selumetinib has been evaluated for many adult and pediatric solid tumors or hematological malignancies as a single agent, 4-12 in combination with cytotoxics, 13-16 or other targeted therapeutic agents. 17 The initial formulation taken into adult phase I trials was a free-base oral suspension, but it exhibited dose-limited absorption due to low.
Phase II trial of the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886 Hydrogen Sulfate) in adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) AstraZeneca and MSD's selumetinib has been recommended for conditional marketing authorisation in the European Union (EU) for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in paediatric patients with neurofibromatosis type 1 (NF1) aged three years and above. 1 NF1 is a debilitating genetic condition affecting 1 in 3,000 individuals worldwide. 2,3 In 30-50% of people. Selumetinib is predominantly excreted in faeces [59% of a single oral 75 mg dose of radiolabelled selumetinib in healthy adults; 19% as the unchanged drug)]; 33% of the dose was recovered in urine (< 1% as the unchanged drug) . Strong correlations were evident between age, height and weight of patients, with moderate to strong correlations. This trial is looking at combining selumetinib with dexamethasone for children and adults with acute lymphoblastic leukaemia (ALL). It is open to people with ALL that has come back after treatment (relapsed) or has continued to get worse during treatment (refractory). And the leukaemia has a gene change (mutation) in the RAS-pathway that controls the MEK protein Selumetinib did not elicit clinical activity in pediatric and young adult patients with refractory cancers who had actionable mutations in the RAS/RAF/MAPK1/2-ERK pathway, according to cohort.
Selumetinib for Plexiform Neurofibromas Neurofibromatosis involves activation of the RAS pathway. Phase 2 trial of the MEK inhibitor PD-0325901 in adolescents and adults with NF1-related. . MEK inhibitors are known to alter the outer blood-retina barrier.4, 5 It is unclear whether the previously reported retinal vein occlusions in adults with advanced cancer were due to MEK inhibitor induced alteration in the outer blood retinal barrier rather than the other known systemic risk factors (eg, hypertension, atherlosclerosis). 5 Over 10 different MEK inhibitors have. Treatment of uveal melanoma. Adjuvant treatment of patients with stage III or stage IV differentiated thyroid cancer. Dymond, Angela W., et al. Metabolism, excretion, and pharmacokinetics of selumetinib, an MEK1/2 inhibitor, in healthy adult male subjects. Clinical therapeutics 38.11 (2016): 2447-2458 The purpose of this study is to see if adding vinblastine to treatment with the drug selumetinib is more effective than selumetinib alone for children and young adults with low-grade glioma (a common type of brain cancer) that has come back after prior treatment or does not respond to therapy
Patients already receiving selumetinib through single patient access who enroll in this protocol must be reconsented and sign the consent form for this intermediate access protocol. 8. For female patients of childbearing potential, have evidence of a post-menopausal status, or a negative urinary or serum pregnancy test It is the most common primary intraocular malignancy in adults and comprises 5% of all melanomas 1,2. Uveal melanoma is a rare and devastating disease for which there are currently no effective treatment options once it spreads beyond the tissues of the eye. Selumetinib could potentially become the first effective treatment for these patients Phase II Trial of the MEK 1/2 inhibitor selumetinib (AZD6344, ARRY-142886 hydrogen sulphate) in adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) [abstract]
Adult Patients: The Kirklin Clinic of UAB Hospital. 1st Floor. 6th Ave South. Birmingham, AL 35233. Parking Information. The UAB Neurofibromatosis Clinic is looking to enroll adults with Neurofibromatosis Type 1 (NF1) for a clinical trial targeting cutaneous neurofibromas using the investigational drug called selumetinib Fingerprint Dive into the research topics of 'Population Pharmacokinetics of Selumetinib and Its Metabolite N-desmethyl-selumetinib in Adult Patients with Advanced Solid Tumors and Children with Low-Grade Gliomas'. Together they form a unique fingerprint. AZD 6244 Medicine & Life Science Phase II Trial of the MEK1/2 Inhibitor Selumetinib (AZD6244 hydrogen sulfate) in Adults with Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas A Pharmacodynamics-Driven Trial of Talazoparib, an Oral PARP Inhibitor, in Patients With Advanced Solid Tumors and Aberrations in Genes Involved in DNA Damage Respons This is a Phase 2 trial to assess the hearing response rate and radiographic response of VS in children and young adults with NF2 who are treated with selumetinib. Dosing will be based on age: For patients with NF2 who are 3 to < 18 years of age, dosing will be based on BSA. Dosing is based on BSA calculated at the beginning of each course
Selumetinib. Neurofibromatosis Type 1, Inoperable plexiform neurofibromas: • Adult or pediatric populations • Should contain rigorously collected patient -reported symptomati A Study of Selumetinib in Chinese Paediatric and Adult Subjects With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas (PN) October 24, 2020 checkorphan. Learn more about: Neurofibromatosis type 1 . Related Clinical Trial The phase 1 trial will examine both adults and children who have had a relapse of their acute Selumetinib works to inhibit enzymes called MEK 1/2 which are critical components of the so-called. . This results in killing tumor cells. Drugs used as chemotherapy, such as carboplatin and vincristine, work in different ways to stop the growth of tumor cells, either by. Selumetinib is currently undergoing evaluation in adult cancers and children with brain tumors and NF1-related plexiform neurofibromas. - In an NCI phase I trial of selumetinib for children and young adults with NF1 and inoperable PN we have observed preliminary activity with PN volume decrease in > 50% of patients enrolled
ATLANTA — Osimertinib plus intermittent selumetinib demonstrated preliminary antitumor activity and acceptable toxicity in patients with EGFR-mutated non-small cell lung cancer whose disease. Gastrointestinal stromal tumors (GIST) are solid tumors that can develop anywhere in the gastrointestinal (GI) tract. Neurofibromatosis type 1 (NF1) is a genetic disorder that causes tumors to form on nerve tissue and is usually diagnosed in children and young adults. Patients with NF1 have an increased risk of developing GIST , with or without NF1 (National Cancer Institute) So, what is selumetinib and why might it be useful to treat symptoms associated with Neurofibromatosis Coyne GO, Gross A, Dombi E, et al. Phase II trial of the MEK 1/2 inhibitor selumetinib (AZD6344, ARRY-142886 hydrogen sulphate) in adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN) Dr. Brigitte Widemann is a pediatric oncologist with the primary interest of developing effective therapies for children and adults with genetic tumor predisposition syndromes, such as neurofibromatosis type 1 (NF1), and rare solid tumors through innovative clinical trial design. Dr. Widemann currently serves as the head of the Pharmacology & Experimental Therapeutics Sectio
The results of pharmacokinetic evaluations of selumetinib among the children in this trial were similar to those published for adults. Treatment with selumetinib resulted in confirmed partial responses (tumor volume decreases from baseline of ≥20%) in 17 of the 24 children (71%) and decreases from baseline in neurofibroma volume in 12 of 18. Background: Neurofibromatosis type 1 (NF1) is a disorder that can cause plexiform neurofibromas (PNs). These are tumors that grow along nerves. Some PNs cause serious health problems. PNs often can t be operated on because of their large size, location, or number. There are no effective treatments known for people with NF1 and PNs. Researchers want to test if the drug selumetinib (AZD6244. Selumetinib in Treating Patients With Neurofibromatosis Type 1 and Cutaneous Neurofibroma; Plexiform neurofibroma trials. Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults (NF105-CABO
Guiding star of science leads AstraZeneca to breakthrough in child tumour therapy. Global product lead George Kirk hails the triumph of selumetinib, which has just won FDA approval. The power of science has been the guiding star for a drug that has weathered storms to land an approval that has given hope to an underserved cohort of children. Selumetinib is a drug that works by blocking some enzymes that low-grade glioma tumor cells need for their growth. This results in killing tumor cells. Drugs used as chemotherapy, such as carboplatin and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by. Free online access to the UK BNF (British National Formulary) content published by NICE - last updated 2 June 2021 If you choose to join this study, you will: - Get study drugs Osimertinib and Selumetinib -- You will take Osimertinib once a day every day and Selumetinib twice a day for 4 days - Have routine eye exams - Have blood samples and possibly a small piece of tissue removed from your lung to see what type of lung cancer cells you have - Have other tests, exams, and procedures for study purposes and.
BOSTON — The investigational MEK inhibitor selumetinib showed clinical responses in adult patients with neurofibromatosis type 1-associated plexiform neurofibromas, according to preliminary results from an ongoing phase II study presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held Oct. 26-30 Selumetinib is an orally administered small molecule, developed by AstraZeneca, for the treatment of neurofibromatosis 1 and various cancers. It inhibits MAP (In Adults, in the elderly, Inoperable/Unresectable) in USA, Italy and Spain (PO) in August 2021 (NCT04924608 Koselugo ® (selumetinib) is the first FDA-approved drug indicated for the treatment of neurofibromatosis type 1 (NFI), a rare and incurable genetic condition, developed and commercialised globally by AstraZeneca and Merck (MSD) under a licensing agreement.. The US Food and Drug Administration (FDA) approved the oral MEK inhibitor, Koselugo (selumetinib) for treating NF1 with symptomatic and. Selumetinib is a small molecule oral drug that inhibits proteins called MEK1 and MEK2, which are involved a signaling pathway that affect cell proliferation and tumor cell survival. Chemotherapy drugs like carboplatin and vincristine work in different ways to stop the growth of tumor cells, either by killing the cells, by preventing them from. Risks of selumetinib are consistent with MAPK (MEK) inhibitor class effects, including ocular, cardiac, musculoskeletal, gastrointestinal, and dermatologic toxicities. Safety was assessed across a pooled database of 74 pediatric patients with plexiform neurofibromas and supported by adult and pediatric selumetinib clinical trial data in cancer.
Koselugo (selumetinib) is a kinase inhibitor that targets mitogen-activated protein kinase (MAPK) 1 and 2 (MEK1/2) and indicated for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). MEK i On April 10, 2020, the FDA approved AstraZeneca's KOSELUGO™ (selumetinib) for the treatment of pediatric patients two years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). Key findings from the FDA's Multi-Discipline Review, Administrative and Correspondence Documents, and Package Insert Selumetinib (MEK inhibitor AZD6244) is a type of medicine called a targeted therapy. Selumetinib acts to block certain cell signals that may help keep cancer cells from growing. Selumetinib is an investigational drug being studied for several types of cancers. Patients will have regular blood draws to check blood counts and to monitor liver and.
A Study of Selumetinib in Chinese Paediatric and Adult Subjects With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas (PN) Condition(s): Neurofibromatosis 1; Neurofibroma Plexiform Last Updated: June 9, 2021 Recruiting. 3. A Study of Selumetinib in Patients With Kaposi's Sarcoma Selumetinib C max and AUC decreased by 60% and 38%, respectively, following a low-fat meal (400 calories, 25% fat) in healthy adults administered a single-dose of 50 mg. T max was delayed by approximately 0.9 hours following a low-fat meal MAINTENANCE: Patients receive carboplatin IV over 60 minutes on days 1, 8, 15, and 22 and vincristine IV or IV push over 1 minute on days 1, 8, and 15. Treatment repeats every 6 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive selumetinib sulfate orally (PO) twice daily (BID) on days 1-28 The primary aim of this analysis was to characterize the population pharmacokinetics of selumetinib and its active metabolite N-desmethyl-selumetinib in patients with cancer. Concentration-time data from adult and pediatric clinical trials were pooled to develop a population pharmacokinetic model using a sequential approach where selumetinib. This situation prompted the assessment of selumetinib, an oral inhibitor of MEK1 and MEK2 in children with NF1, on the basis of promising activity in adults with several types of advanced-stage.
and patients treated with any dose of selumetinib. Subgroup safety analyses based on dose level in pediatric populations and in adult populations receiving single agent selumetinib will also be conducted and submitted in the NDA. • With the proposal to include summary safety data from patients treated in th Treatment repeats every 42 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive selumetinib sulfate orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 27 cycles in the absence of disease progression or unacceptable toxicity recently published phase II study of selumetinib in recurrent LGGs in NF1 patients evaluated 25 patients, 40% of whom demonstrated a partial response to the medication. In addi-tion, 96% of patients had 2 years of progression free survival and only one subject had progression of their tumor while on therapy [19, 20]. Of the NF1 patients treated. Therefore, a randomized phase II trial of selumetinib vs selumetinib plus temsirolimus was conducted.Methods:Seventy-one adults with advanced STS who received ≤2 prior chemotherapeutics were randomized to selumetinib 75 mg p.o. bid and allowed to crossover upon progression, or to selumetinib 50 mg p.o. bid plus temsirolimus 20 mg i.v. weekly. I. To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of selumetinib sulfate (selumetinib) + vinblastine sulfate (vinblastine) for children with progressive or recurrent low-grade gliomas (LGGs). II. To determine if selumetinib + vinblastine will lead to improved event-free survival (EFS) outcome compared with selumetinib alone for children with progressive or.
Selumetinib, an oral MEK inhibitor, demonstrated clinical benefit without significant toxicity in adult patients affected by symptomatic neurofibromatosis type 1 (NF1) with associated plexiform neurofibromas (PN), according to Geraldine O'Sullivan Coyne, MD, PhD, in a preconference briefing of the 2019 American Association for Cancer Research-National Cancer Institute-European. Clinical trial for Lymphocytic Leukemia | leukemia | childhood ALL | Acute Lymphoblastic Leukemia | Acute Lymphoblastic Leukemia Recurrent | acute lymphoblastic | acute lymphoid leukaemia | acute lymphocytic leukemia | acute lymphoblastic leukemia | in Relapse | Adult | Acute | acute lymphoblastic leukemia (all) , International Trial of Selumetinib in Combination With Dexamethasone for the. Selumetinib was also successfully applied in NF1 patients with spinal neurofibromas and was shown to reduce tumor burden, effect on the spinal canal, cerebrospinal fluid distribution, and spinal cord shape in 18 of 24 patients . In one pilot study selumetinib is applied to reduce the size and number of neurofibromas in adult NF1 patients. If you choose to join this study, you will: - Get study drugs Osimertinib and Selumetinib. -- You will take Osimertinib once a day every day and Selumetinib twice a day for 4 days. - Have routine eye exams. - Have blood samples and possibly a small piece of tissue removed from your lung to see what type of lung cancer cells you have Drug Approval Package: KOSELUGO. Company: AstraZeneca Pharmaceuticals LP. Application Number: 213756. Approval Date: 04/10/2020. Drugs@FDA information available about KOSELUGO. Persons with disabilities having problems accessing the PDF files below may call (301) 796-3634 for assistance. FDA Approval Letter and Labeling
Purpose Uveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent activity in patients with metastatic uveal. .7 Further regulatory submissions are underway. Clinical trials of selumetinib in adult patients with NF1 PN, and in an alternative age-appropriate formulation for paediatric patients.
Selumetinib is a MEK1/2 inhibitor. The clinical trials of selumetinib in adult patients with NF1 PN, and in an alternative age-appropriate formulation for pediatric patients, are expected to be initiated in 202 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 Syst Pharmacol 6:305-314, 2017 (2) Open-label, Phase 2 Clinical Trial of Crizotinib for Children and Adults with Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas. This Phase 2 trial will determine the response rate to crizotinib in children and adult NF2 patients with vestibular schwannomas, and determine safety and tolerability of treatment in these cohorts
The results of a new study show that the MEK1 and 2 inhibitor selumetinib is well-tolerated and associated with tumour shrinkage in children with inoperable plexiform neurofibromas. The phase 1 trial enrolled 24 patients aged 3-18 years who had neurofibromatosis type 1-related plexiform neurofibromas. The patients received a continuous schedule of oral selumetinib in 28-day cycles Koselugo (selumetinib) Onco360® has been selected by AstraZeneca to be a specialty pharmacy partner for KOSELUGO™ (selumetinib), a novel oral kinase inhibitor indicated for the treatment of pediatric patients aged two years and above, with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas. March 13, 2020