Intravenous and Intrathecal Nivolumab in Treating Patients With Leptomeningeal Disease

Running, not enrolling · Phase 1

Conditions studied: 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

In brief

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.

Key facts

Study ID: NCT03025256
Run by: M.D. Anderson Cancer Center
People needed: 75
Starts: 2018-05-02
Expected to finish: 2027-06-01
Last updated by the study team: 2026-06-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients must have radiographic and/or CSF cytological evidence of LMD. For patient with melanoma: Must have a confirmed diagnosis of primary central nervous system (CNS) melanoma, melanocytomas or metastatic melanoma (cutaneous, acral-lentiginous, uveal and mucosal in origin), based on histological analysis of metastatic tissue and/or cancer cells, archival tissue permitted. For patients with lung cancer: non-small cell, based on histological analysis of metastatic tissue and/or cancer cells, archival tissue permitted
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of =< 2
Patients may receive steroids to control symptoms related to CNS involvement, but the dose must be =< 4 mg per 24 hours of dexamethasone (or the equivalent). Physiologic replacement doses for adrenal insufficiency is allowed on this protocol
Patients who have received radiation to brain and/or spine, including whole brain radiation, stereotactic radiosurgery, or stereotactic body radiation therapy (SBRT), are eligible, but must have completed radiation treatment at least 7 days prior to the start of treatment
Patients who have been treated with an approved targeted therapy (BRAF inhibitor and/or MEK inhibitor) will be allowed to remain on concurrent approved targeted therapy. No other concomitant intrathecal therapy with another agent will be allowed. For patients that have received other systemic therapies, the minimum wash out period is as follows:
Patients that received previous IT therapy must have received their last treatment >= 7 days prior to the start of treatment
Patients who have received systemic chemotherapy must have received their last treatment >= 14 days prior to the start of treatment
Patients who have received an approved systemic biologic therapy (e.g. anti-PD-1, anti-CTLA4, IL2, interferon) must have received their last treatment >= 2 weeks prior to the start of treatment
Patients who have received any other investigational agents must have received their last treatment >= 14 days prior to the start of treatment
For patients with lung cancer:
For chemotherapy: patients do not require a washout period, and can continue with chemotherapy during treatment with IT/IV nivolumab
Patients who have received an approved systemic biologic therapy (e.g. anti-PD-1, anti-CTLA4, IL2, interferon) must have received their last treatment >= 2 weeks prior to the start of treatment
Patients who have received any other investigational agents must have received their last treatment >= 14 days prior to the start of treatment
No other concomitant intrathecal therapy with another agent will be allowed
Patients who are receiving treatment to tyrosine kinase inhibitors or other targeted therapy agents do not require a washout period, and can continue with tyrosine kinase inhibitors or other targeted therapy agents during treatment with IT/IV nivolumab
Age >= 18 years
Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Absolute neutrophil count (ANC) >= 1.5 X 10\^9/L
Hemoglobin >= 9.0 g/dL
Platelets >= 75 X 10\^9/L
Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 X upper limit of normal (ULN)
Total bilirubin: =< 1.5 X ULN (isolated bilirubin > 1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X ULN
Albumin >= 2.5 g/dL
Creatinine OR =< 2 x ULN; calculated creatinine clearance OR >= 50 mL/min; 24-hour urine creatinine clearance >= 50 mL/min

You may not qualify if…

Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Subjects with a condition requiring systemic treatment with either corticosteroids (> 4 mg daily dexamethasone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Tocilizumab and vedolizumab are permitted, as are inhaled or topical steroids and adrenal replacement doses in the absence of active autoimmune disease
Subjects that require premedication with corticosteroids for a contrast allergy are excluded from this restriction and can proceed with enrollment
Patients who have previously received alpha-PD-1 and/or anti-CTLA-4 will be eligible, unless they have ongoing > grade 2 adverse event (AE) side effects of such therapy. Ongoing physiologic replacement doses for adrenal and thyroid insufficiency are allowed on protocol
Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug (concurrent treatment with approved targeted therapies is allowed.)
Pregnant or lactating female
Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled
Patients with a history of pneumonitis
Evidence of active infections =< 7 days prior to initiation of study drug therapy (does not apply to viral infections that are presumed to be associated with the underlying tumor type required for study entry)
Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 12 weeks prior to study drug
Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) even if fully immunocompetent on antiretroviral therapy (ART)-due to the unknown effects of HIV on the immune response to combined nivolumab or the unique toxicity spectrum of these drugs in patients with HIV
History of allergy to study drug components
History of severe hypersensitivity reaction to any monoclonal antibody
Prisoners or subjects who are involuntarily incarcerated
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness

Where it is running

M D Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

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