Study of Concurrent Intravenous and Intrathecal Nivolumab for Patients With Leptomeningeal Disease (LMD)
This clinical research study consists of 2 phases: dose escalation (Phase 1) and dose expansion (Phase 2).
The goal of Phase 1 of this research study is to find the highest tolerable dose level of nivolumab that can be given both by intravenous (IV) infusion and intrathecal (IT) injection to patients with leptomeningeal disease (LMD). IV infusions are given by vein, while IT injections are given directly into the cerebrospinal fluid (CSF).
The goal of Phase 2 of this research study is to learn if the highest tolerable dose level combination found during Phase 1 can help to control the disease.
The safety of the drug combination will also be studied in both phases.
|Melanoma and Other Malignant Neoplasms of Skin Leptomeningeal Disease||Drug: Nivolumab||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase I/Ib Study of Concurrent Intravenous and Intrathecal Nivolumab for Patients With Leptomeningeal Disease (LMD)|
- Recommended Dose of Combined IT and IV Nivolumab [ Time Frame: 28 days ]Recommended dose defined as the highest dose for which the posterior probability of toxicity is closest to 30%.
- Overall Survival (OS) with Combined IT and IV Nivolumab [ Time Frame: 12 months ]Kaplan-Meier method used to estimate the distribution of OS from the start of study treatment.
|Anticipated Study Start Date:||September 2017|
|Estimated Study Completion Date:||September 2020|
|Estimated Primary Completion Date:||September 2020 (Final data collection date for primary outcome measure)|
Dose Escalation: Participants receive intrathecal (IT) Nivolumab every 14 days. Cycle 1 consists of IT Nivolumab only, but in subsequent cycles the IT Nivolumab dose is followed by an intervenous dose of Nivolumab.
Intrathecal dose administered by accessing the Ommaya.
Dose Expansion: Maximum tolerated dose from Dose Escalation.
Dose Escalation Intrathecal Nivolumab Starting Dose: 10 mg as an injection directly into CSF through Ommaya reservoir on Day 1 of each 14 day cycle for 2 cycles.
No intrasubject dose escalation, and subjects receive the same IT dose level during all subsequent cycles for up to 2 years, given tolerability.
Intravenous dose is 3 mg/kg for all participants.
Dose Expansion Intrathecal Nivolumab: Recommended dose from Intrathecal Nivolumab Dose Escalation Phase
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Please refer to this study by its ClinicalTrials.gov identifier: NCT03025256
|Contact: Isabella C. Glitza, MD, PHD||713-792-2921||CR_Study_Registration@mdanderson.org|
|Contact: Clinical Research Operations MD Anderson Cancer Center||713-792-7734||CR_Study_Registration@mdanderson.org|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Not yet recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Isabella C. Glitza, MD, PHD||M.D. Anderson Cancer Center|