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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 1INTERVENTIONAL

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)

Intravenous and Intrathecal Nivolumab in Treating Patients With Leptomeningeal Disease (NCT03025256) is a Phase 1 interventional studying Acral Lentiginous Melanoma and Central Nervous System Melanoma, sponsored by M.D. Anderson Cancer Center. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Acral Lentiginous Melanoma, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 75 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Acral Lentiginous Melanoma subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * 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 * Absence of contraindication for Ommaya reservoir * Women are eligible to participate if: * Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/mL and estradiol \< 40 pg/mL (\<140 pmol/L) is confirmatory\] * A Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level \> 40mIU/mL to confirm menopause * Females treated with hormone replacement therapy, (HRT) are likely to have artificially suppressed FSH levels and may require a washout period in order to obtain a physiologic FSH level. The duration of the washout period is a function of the type of HRT used. The duration of the washout period below are suggested guidelines and the investigators should use their judgment in checking serum FSH levels. If the serum FSH level is \>40 mIU/ml at any time during the washout period, the woman can be considered postmenopausal: * 1 week minimum for vaginal hormonal products (rings, creams, gels) * 4 week minimum for transdermal products * 8 week minimum for oral products * Other parenteral products may require washout periods as long as 6 months * A Women of childbearing potential agrees to use method(s) of contraception. For a teratogenic study drug and/or when there is insufficient information to assess teratogenicity (preclinical studies have not been done), a highly effective method(s) of contraception (failure rate of less than 1% per year) is required. The individual methods of contraception and duration should be determined in consultation with the investigator. Women of childbearing potential (WOCBP) must follow instructions for birth control when the half-life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 30 days plus the time required for the investigational drug to undergo five half-lives. The half-life of nivolumab is up to 25 days. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of investigational product * Women must not be breastfeeding * Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year The investigator shall review contraception methods and the time period that contraception must be followed. Men who are sexually active with WOCBP must follow instructions for birth control when the half-life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 90 days plus the time required for the investigational drug to undergo five half-lives. The half-life of nivolumab is up to 25 days. Therefore, men who are sexually active with WOCBP must continue contraception for 31 weeks (90 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug * Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile and azoospermic men do not require contraception Exclusion Criteria: * 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

Treatments Being Tested

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

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

M D Anderson Cancer Center
Houston, Texas, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT03025256), the sponsor (M.D. Anderson Cancer Center), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT03025256 clinical trial studying?

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. The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT03025256?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT03025256?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT03025256. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT03025256. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.