NCT03025256

Intravenous and Intrathecal Nivolumab in Treating Patients With Leptomeningeal Disease

Phase I/Ib Study of Concurrent Intravenous and Intrathecal Nivolumab for Melanoma and Lung Cancer Patients With Leptomeningeal Disease (LMD)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 75 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/Ib trial studies the side effects and best dose of intrathecal nivolumab, and how well it works in combination with intravenous nivolumab in treating patients with leptomeningeal disease. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed description

PRIMARY OBJECTIVE: I. To determine the safety and/or recommended dose of intrathecal (IT) nivolumab in combination with systemic nivolumab treatment in melanoma and lung cancer with leptomeningeal disease (LMD). SECONDARY OBJECTIVE: I. To assess overall survival with combined intrathecal and systemic administration of nivolumab in this patient population. EXPLORATORY OBJECTIVES: I. Compare the immunological effects of this treatment on immune cells in the cerebrospinal fluid (CSF) to those observed in the peripheral blood and in non-LMD tumors. II. Evaluation of predictors (clinical, molecular, and/or immune) of the efficacy and safety of this regimen. III. To assess the effect of nivolumab on subsequent treatment. IV. To compare levels of nivolumab in the CSF and peripheral blood. OUTLINE: This is a phase I, dose-escalation study followed by a phase Ib study. Patients receive nivolumab IT over 5 minutes on day 1 of every cycle. Beginning in cycle 2, patients also receive nivolumab intravenously (IV) over 30 minutes on day 1 (4 hours after the IT dose). Cycles repeat every 14 days for 18 cycles and then every 28 days (cycles 19 and beyond) in the absence of disease progression or unacceptable toxicity. Patients will have CSF and blood specimen collection on days 1, 2, 8 of each cycle and end of treatment. Patients undergo computed tomography (CT) or positron emission tomography (PET) at baseline, cycle 5 and then every 8 weeks. Patients undergo magnetic resonance imaging (MRI) at baseline, cycles 3, 5, and then every 8 weeks. After completion of study treatment, patients are followed up within 4 weeks and then every 12 weeks thereafter.

Conditions

• Acral Lentiginous Melanoma
• Central Nervous System Melanoma
• Clinical Stage IV Cutaneous Melanoma AJCC v8
• Leptomeningeal Neoplasm
• Melanocytoma
• Metastatic Lung Non-Small Cell Carcinoma
• Metastatic Melanoma
• Metastatic Mucosal Melanoma
• Metastatic Uveal Melanoma
• Stage IV Lung Cancer AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Correlative studies
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Lumbar Puncture	Undergo lumbar puncture for cerebrospinal fluid collection
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI of brain and spine
BIOLOGICAL	Nivolumab	Given IV or IT
PROCEDURE	Positron Emission Tomography	Undergo PET

Timeline

• Start date: 2018-05-02
• Primary completion: 2027-06-01
• Completion: 2027-06-01
• First posted: 2017-01-19
• Last updated: 2026-04-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study