About Perlmutter Cancer Center | NYU Langone Health
NYU Langone’s Perlmutter Cancer Center is an NCI-designated Comprehensive Cancer Center.
About the Left Ventricular Assist Device | NYU Langone Health
NYU Langone doctors use left ventricular assist device (LVAD) therapy to improve and prolong life for people with advanced heart failure.
Accepted Insurance Plans for Urgent Care at NYU Langone | NYU Langone Health
Urgent care services performed at NYU Langone are covered by a variety of insurance plans.
Accessibility | NYU Langone Health
At NYU Langone Health, we strive to provide excellent digital access to all.
Achalasia | NYU Langone Health
NYU Langone doctors use imaging tests to diagnose achalasia, a swallowing disorder, and offer medical, endoscopic, and surgical treatment.
Achilles Injury | NYU Langone Health
NYU Langone doctors diagnose and provide comprehensive treatment for Achilles injuries, including tendinitis and ruptures.
Achondroplasia in Children | NYU Langone Health
Doctors at Hassenfeld Children’s Hospital at NYU Langone offer diagnosis, treatment, and support for children with achondroplasia.
Acne | NYU Langone Health
Acne is a chronic skin condition characterized by blemishes on the face, chest, and back that can be well managed with noninvasive treatments.
ACNS1831: A Phase 3 Randomized Study of Selumetinib (IND # 77782) versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) Associated Low-Grade Glioma (LGG)
Low-grade gliomas (LGG) are the most common central nervous system (CNS) tumors in the pediatric population. Although the etiology of most childhood LGG is unknown, children with the genetic disorder Neurofibromatosis type 1 (NF1) are at increased risk of developing LGG, most commonly within the optic pathway. This sensitive location makes surgical resection difficult and fraught with morbidities. Radiation therapy has proven effective in the treatment of LGG, however, toxicity from radiation is significant, especially in children with NF1 where the risk of a radiation-induced secondary malignancy and vascular disease is increased. Therefore, most experts agree that the first line standard of care in treating NF1-associated LGG is chemotherapy. Since the vast majority of patients will not succumb to their disease, treatment is often focused on preserving or improving functional outcomes, particularly visual acuity. This differs from patients without NF1, where tumor growth is typically the primary characteristic utilized in making treatment decisions. In the CCG A9952 trial, children with NF1-associated LGG were non-randomly assigned to the carboplatin and vincristine (CV) arm given the potential risk of secondary malignancy with the alkylating-containing regimen (thioguanine, procarbazine, CCNU, and vincristine). The 5-year event-free survival rate was 69% ± 4% for the NF1 group and 39% ± 4% for patients without NF1 who were randomly assigned to CV (P < 0.001). Most experts would agree that CV is considered the standard of care in patients with NF1-associated LGG that require treatment. Recently, major advancements in the understanding of the molecular pathways implicated in pediatric LGG have been made. The most frequent genetic aberrations involve the mitogen-activated protein kinase (MAPK) pathway, most commonly due to activation of BRAF through a tandem duplication that results in the KIAA1549-BRAF fusion or an activating BRAF point mutation (BRAFV600E). NF1 also activates the same RAS/RAF/MAPK cascade, suggesting a common pathway in the majority of LGG. Novel drug development has now allowed for the manipulation and targeting of the MAPK pathway in the treatment of LGG. Selumetinib (AZD6244/ ARRY-142886) is a potent, selective, orally-available, non-ATP competitive small molecule inhibitor of MEK-1/2 which lies downstream of BRAF. The Pediatric Brain Tumor Consortium (PBTC) phase 1 and phase 2 selumetinib trial data showed unprecedented responses and activity in children with multiply recurrent LGG, particularly in NF1-associated LGG. These data led to the development of this study, which is a prospective randomized phase 3 study comparing selumetinib to CV in previously untreated NF1-associated LGG. This study will compare both the event-free survival (EFS) and visual functional outcomes (primarily assessed by Teller Acuity Cards) between the two randomized arms.
ACNS1833: A Phase 3 Randomized Non-Inferiority Study of Carboplatin and Vincristine versus Selumetinib (NSC# 748727 IND# 77782) in Newly Diagnosed or Previously Untreated Low-Grade Glioma (LGG) not associated with BRAFV600E Mutations or Systemic Neurofibromatosis Type 1 (NF1)
Site for Low-grade gliomas (LGG) are the most common central nervous system tumor among children, accounting for approximately one-third of pediatric brain tumors. These tumors include a heterogeneous group of astrocytic, oligodendroglial and mixed glial-neuronal histologies that can occur anywhere in the brain or spinal cord. Although complete surgical resection is the mainstay of therapy whenever feasible, tumors that are unresectable often require additional therapy. Radiation therapy is an effective treatment option for pediatric LGG, but it may result in significant morbidities, including cognitive decline, endocrine deficiencies, secondary malignancies, vascular damage, or growth abnormalities. Since the 1980s, chemotherapy has been used to delay or obviate the need for radiation therapy and reduce the overall therapy-associated morbidity in pediatric LGG. Two commonly used chemotherapy regimens (carboplatin and vincristine [CV] and a combination of thioguanine, procarbazine, lomustine and vincristine [TPCV]) were directly compared in the CCG trial A9952 among children with LGG not associated with neurofibromatosis type 1. CV resulted in a slightly lower 5-year event free survival than TPCV; however, CV avoids the risks of secondary malignancy and infertility posed by the TPCV regimen and remains the most popular chemotherapy regimen with the most robust historical data for children with LGG.Recent advances in our understanding of the biology of pediatric LGG have identified the critical role of activation of the mitogen-activated protein kinase (MAPK) pathway, most commonly due to activation of BRAF through a tandem duplication that results in the KIAA1549-BRAF fusion or an activating BRAF point mutation (BRAFV600E). This discovery has paved the way for the development of drugs that target the MAPK pathway. Selumetinib (AZD6244; ARRY-142886) is a potent, selective, orally-available, non-ATP competitive small molecule inhibitor of MEK-1/2 that lies downstream of BRAF. Phase 1 and phase 2 selumetinib trial data have shown excellent responses and activity in children with multiply recurrent LGG with and without the most common BRAF aberrations. As an alternative to CV, selumetinib may offer reduced cytotoxicity, easier administration (oral) and improved quality of life with the potential for similar or improved efficacy.ACNS1833 is a prospective randomized phase 3 study comparing selumetinib to CV in previously untreated LGG not associated with neurofibromatosis or BRAFV600E. This non-inferiority study will compare event- free survival, functional/behavioral outcomes and quality of life measures for patients treated with CV versus selumetinib.