Research in the Neuro-Oncology division focuses on the treatment of primary brain tumors. Faculty members are engaged in a number of clinical trials and leading collaborative lab-based research involving novel treatment modalities and cellular responses to therapeutics. The close collaboration between clinical and basic science investigations fosters translational research and thus results in cutting edge patient care.
Faculty members in the Neuro-Oncology Division are leading research in the following areas:
Dr. Moots’ research activities focus on chemotherapy trials for patients with primary CNS neoplasms. He leads ongoing trials for recurrent anaplastic astrocytoma, IDH mutated gliomas, and progressive plexiform neurofibromas in patient with NF1. Prior trials have included various newly diagnosed gliomas, medulloblastoma, ependymoma, CNS lymphoma and carcinomatous meningitis. He was the study chair for an ECOG adult medulloblastoma trial.
Dr. Clark’s research focuses on clinical trial development and translational work for tumors of the CNS including glioblastoma, anaplastic glioma, low-grade glioma, meningioma. He recently completed a phase I trial of epigenetic modification in recurrent glioblastoma. This clinical trial included laboratory investigations of tumor DNA methylation patterns before and after treatment. Dr. Clark has laboratory projects assessing DNA methylation patterns and their changes and response to chemotherapy in glioblastoma model systems using zebrafish implants and organoid cultures.
Brain Tumor Stem Cells
Dr. Cooper’s research interests involve brain tumor stem cells and the development of new antibodies to recognize glioma cells. The Cooper laboratory studies brain tumor cellular heterogeneity with respect to molecular pathways that drive glioma cell growth and adaptive responses to therapeutic modalities. Towards these goals, the laboratory utilizes a patient tissue repository to identify the specific glioma subtypes in which the Hedgehog signaling pathway is operational and activated. Dr. Cooper’s research team has established a preclinical model for growing human malignant gliomas in mice to demonstrate that Hedgehog signaling regulates glioma growth and that pathway inhibition enhances survival. The Hh pathway appears to be activated in a subset of glioma cells (CD133+ cells), and determining how Hh signaling impacts this cellular compartment in gliomas is a primary focus of research. Longer term goals of these preclinical studies are to design clinical trials of Hedgehog inhibitors based upon selecting patients with malignant glioma who might best respond to Hedgehog inhibitors, defining the mechanism of action of Hedgehog pathway inhibition on glioma cancer stem cells and avoiding potential mechanisms of drug resistance.
Adult Brain Tumor Trials:
- Phase III study comparing three cycles of BCNU/Cisplatin followed by radiation therapy with radiation therapy and concurrent BCNU for patients with newly diagnosed supratentorial glioblastoma (ECOG 2394).
- Phase III randomized study of SU101 versus procarbazine for patients with glioblastoma in first relapse (IN NEU 9805).
- Phase III intergroup randomized comparison of radiation alone vs pre-radiation chemotherapy for pure and mixed anaplastic oligodendrogliomas (RTOG 9402).
- Phase II trial of preradiation multiagent chemotherapy for adults with "poor-risk" medulloblastoma, PNET, and disseminated ependymoma (ECOG 4397).
- VICC MD 1188 - An open-label, phase II study of vemurafenib in patients with BRAF V600 mutation-positive cancers.
- NCICIRB - ECOG NEU E3F05 Phase III Study of Radiation Therapy with or without Temozolomide for Symptomatic or Progressive Low-Grade Gliomas
- NCICIRB - ECOGNEUN0577- Phase III Intergroup Study of Temozolomide Alone versus Radiotherapy with Concomitant and Adjuvant Temozolomide versus Radiotherapy with Adjuvant PCV Chemotherapy in Patients with 1p/19q Co-deleted Anaplastic Glioma (NCCTGN0577)
- NEU 1670-A Phase 3, Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Eflornithine with Lomustine Compared to Lomustine Alone in Patients with Anaplastic Astrocytoma that Progress/Recur After Irradiation and Adjuvant Temozolomide Chemotherapy - STELLAR Study
- Meningiomas with SMO/AKT/NF2 Mutations
- ECOGNEUA071102- A Phase II/III Randomized Trial Of Veliparib Or Placebo In Combination With Adjuvant Temozolomide In Newly Diagnosed Glioblastoma With MGMT Promoter Hypermethylation
- VICCNEU1997 - A Phase 2b Trial of the MEK 1/2 Inhibitor (MEKi) PD-0325901 in Adult and Pediatric Patients with Neurofibromatosis Type 1 (NF1)-Associated Inoperable Plexiform Neurofibromas (PNs) that are Causing Significant Morbidity
- VICCNEU1165 - A Phase III Clinical Trial Evaluating DCVax-L, Autologous Dendritic Cells Pulsed with Tumor Lysate Antigen for the Treatment of Glioblastoma Multiforme
- VICCNEU15105 - A Phase 2/3 Randomized, Open-Label Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC versus Standard of Care in Subjects Undergoing Planned Resection for Recurrent Glioblastoma or Anaplastic Astrocytoma
- VICCNEU1688 - A Randomized Phase 3 Single Blind Study of Temozolomide plus Radiation Therapy combined with Nivolumab or Placebo in Newly Diagnosed Adult Subjects with MGMT-Methylated (tumor O6-methylguanine DNA methyltransferase) Glioblastoma
- (NEU1308)A Phase I/II Study of High-dose L-methylfolate in combination Temozolomide and Bevacizumab in Recurrent High Grade Glioma
- VICCMD15110 - A Phase 2 Basket Study of the Oral TRK Inhibitor larotrectinib in Subjects with NTRK Fusion-Positive Tumors
- MD 1932 (MK-3475-587-01): A Multicenter, Open label, Phase III Extension Trial to Study the Long-term Safety and Efficacy in Participants with Advanced Tumors Who Are Currently on Treatment or in Follow-up in a Pembrolizumab Trial.
- VICCNEU2015 - A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study of AG-881 in Subjects with Residual or Recurrent Grade 2 Glioma with an IDH1 or IDH2 Mutation.
Metastatic Brain Tumors:
- Phase III randomized trial of Gadolinium Texaphyrin injection as a radiation sensitizer in patients receiving whole brain radiation therapy for the treatment of brain metastases (IN NEU 9843).
- Phase III trial comparing whole brain irradiaiton with versus without stereotactic radiosurgery boost for patients with one to three unresected brain metastases (RTOG NEU 9508).
- Randomized clinical study to determine the efficacy and safety of DepoFoam encapsulated Cytarabine relative to standard therapy for the treatment of neoplastic meningitis in patients with leukemia, lymphoma, or solid tumors (VCC CNS 3).
- Phase IV multicenter clinical study of DepoFoam encapsulated Cytarabine in the treatment of neoplstic meningitis in patients with solid tumors, including primary brain tumors (VCC CNS 4).
- NCI CIRB: ECOGNEUA221208 - Randomized Phase II Study: Corticosteroids + Bevacizumab vs. Corticosteroids + Placebo (BEST) for Radionecrosis after Radiosurgery for Brain Metastases