This early phase I/phase I trial tests the safety, side effects, and best dose of NB005 in combination with radiation therapy, with or without temozolomide, in treating patients with high grade gliomas (HGGs) and leptomeningeal metastasis. HGG is a type of fast and uncontrollably growing brain tumor that starts in brain cells called glial cells and invades surrounding brain tissue, making it difficult to treat. Leptomeningeal metastasis are a serious problem that may occur in cancer in which tumor cells spread from the original (primary) tumor to the meninges (thin layers of tissue that cover and protect the brain and spinal cord). It can happen in many types of tumors. NB005 works by targeting deoxyribonucleic acid (DNA) repair in tumors and is often tested with other treatments, like radiation, to check if it's safe and effective. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Proton craniospinal irradiation (pCSI) is a type of radiation treatment that uses proton beams to treat the whole brain and spine. It helps target the tumor while protecting healthy parts of the body as much as possible. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Giving NB005 with radiation therapy, with or without temozolomide, may be a safe treatment for patients with HGGs and leptomeningeal metastasis.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06829173.
Locations matching your search criteria
United States
New York
New York
Laura and Isaac Perlmutter Cancer Center at NYU LangoneStatus: Active
Contact: Jonathan T Yang
Phone: 212-731-6030
PRIMARY OBJECTIVES:
I. To evaluate the effect of ATM kinase/DNA-dependent protein kinase (DNA-PK) inhibitor NB005 (NB005) in combination with radiation therapy (RT) on rates of cell proliferation and cell death in patients with newly diagnosed high grade gliomas (HGG). (Phase 0)
II. Conduct four distinct dose-finding assessments to determine the safety and tolerability of NB005: (Phase I)
IIa. Dose-finding of NB005 in combination with RT in patients with recurrent HGG (Cohort A).
III. The maximum tolerated dose (MTD) in Cohort A will suggest the starting doses for the pre-surgical dose and dose for Cohorts B, C and D below: (Phase I)
IIIa. Pre-surgical dose-finding of NB005 in combination with RT for newly diagnosed HGG;
IIIb. Post-surgical dose-finding of NB005 in combination with RT for newly diagnosed O6-Methylguanine-DNA methyltransferase (MGMT) unmethylated HGG (Cohort B);
IIIc. Post-surgical dose-finding of NB005 in combination with RT and temozolomide for newly diagnosed MGMT methylated HGG (Cohort C).
IIId. Dose-finding of NB005 in combination with RT for solid tumor leptomeningeal metastasis (Cohort D).
SECONDARY OBJECTIVES:
I. To determine progression-free survival (PFS) as per Response Assessment in Neuro-Oncology (RANO) 2.0 for Cohorts A, B, C and D.
II. To determine overall survival (OS) for Cohorts A, B, C, and D.
III. To determine NB005 pharmacokinetics (PK) and pharmacodynamics (PD) in resected tumor tissue.
OUTLINE: This is a dose-escalation study of NB005 and RT with or without temozolomide, followed by a dose-expansion study. Patients are assigned to 1 of 3 groups.
GROUP I (COHORT A): Patients receive NB005 orally (PO) twice weekly (BIW) on days 1 and 4 of each week or three times weekly (TIW) on days 1, 3, and 5 of each week, as well as standard RT once daily (QW), 5 days per week for 10 treatment fractions. Treatment continues for 42 days in the absence of disease progression or unacceptable toxicity.
GROUP II: Patients receive NB005 PO BIW on days 1 and 4 of each week or TIW on days 1, 3, and 5 of each week and standard RT "boost" QW, 5 days per week for 7 treatment fractions in the absence of disease progression or unacceptable toxicity. Patients then receive NB005 PO at 2 hours prior to standard surgical resection. After completion of surgical resection, patients are assigned to 1 of 2 cohorts based on MGMT methylation status.
COHORT B (MGMT UNMETHYLATED): Patients receive NB005 PO TIW on days 1, 3, and 5 of each week and standard RT QW, 5 days per week for 23 treatment fractions. Treatment continues for 89 days in the absence of disease progression or unacceptable toxicity.
COHORT C (MGMT METHYLATED): Patients receive NB005 PO TIW on days 1, 3, and 5 of each week, temozolomide daily, and standard RT QW, 5 days per week for 23 treatment fractions. Treatment continues for 89 days in the absence of disease progression or unacceptable toxicity.
GROUP III (COHORT D): Patients receive NB005 PO TIW on radiation days 1, 3, 5, 6, 8, and 10 and undergo pCSI for up to 10 treatments in the absence of disease progression or unacceptable toxicity.
All patients also undergo magnetic resonance imaging (MRI) during screening, as well as computed tomography (CT) and blood sample collection throughout the study.
After completion of study treatment, patients are followed every 6 months for 5 years.
Lead OrganizationLaura and Isaac Perlmutter Cancer Center at NYU Langone
Principal InvestigatorJonathan T Yang
