Intravenous and Intrathecal Nivolumab in Treating Patients With Leptomeningeal Disease
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|ClinicalTrials.gov Identifier: NCT03025256|
Recruitment Status : Recruiting
First Posted : January 19, 2017
Last Update Posted : December 16, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acral Lentiginous Melanoma Central Nervous System Melanoma Clinical Stage IV Cutaneous Melanoma AJCC v8 Leptomeningeal Neoplasm Melanocytoma Metastatic Melanoma Metastatic Uveal Melanoma Mucosal Melanoma Pathologic Stage IV Cutaneous Melanoma AJCC v8||Biological: Nivolumab||Phase 1|
I. To determine the safety and/or recommended dose of intrathecal (IT) nivolumab in combination with systemic nivolumab treatment in patients with leptomeningeal disease (LMD).
I. To assess overall survival with combined intrathecal and systemic administration of nivolumab in this patient population.
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. Beginning in cycle 2, patients also receive nivolumab intravenously (IV) over 60 minutes on day 2. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 4 weeks and then every 12 weeks thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/Ib Study of Concurrent Intravenous and Intrathecal Nivolumab for Patients With Leptomeningeal Disease (LMD)|
|Actual Study Start Date :||May 2, 2018|
|Estimated Primary Completion Date :||December 30, 2020|
|Estimated Study Completion Date :||December 30, 2020|
Experimental: Treatment (nivolumab)
Patients receive nivolumab IT over 5 minutes on day 1. Beginning in cycle 2, patients also receive nivolumab IV over 60 minutes on day 2. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Given IV or IT
- Incidence of adverse events [ Time Frame: Up to 2 years ]Safety and tolerability of treatment will be assessed by vital signs, laboratory assessments, adverse events, and serious adverse events for the safety population. Adverse events will be graded by the Common Terminology Criteria for Adverse Events version 4.0. Categorical measures will be summarized using frequencies and percentages while continuous variables will be summarized using mean, standard deviation, median, minimum, and maximum.
- Recommended dose of combined intrathecal (IT) and intravenous (IV) nivolumab defined as the highest dose for which the posterior probability of toxicity is closest to 30% (dose escalation part) [ Time Frame: Up to 28 days ]The Bayesian modified toxicity probability interval method will be used to find the recommended dose.
- Overall survival (OS) in patients treated with IT and IV nivolumab (dose expansion part) [ Time Frame: Up to 2 years ]
- OS [ Time Frame: Up to 2 years ]The Kaplan-Meier method will be used to estimate the distribution of OS from the start of study treatment, and Cox proportional hazard regression will be used to assess the relationship between OS and various covariates of interest, including but not limited to patient demographics, tumor characteristics, disease characteristics, and the expression of biomarkers.
- Immunological effects of nivolumab [ Time Frame: Up to 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03025256
|Contact: Isabella C. Glitza||713-792-2921||ICGlitza@mdanderson.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Isabella C. Glitza 713-792-2921|
|Principal Investigator: Isabella C. Glitza|
|Principal Investigator:||Isabella C Glitza||M.D. Anderson Cancer Center|