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)
2 other identifiers
interventional
75
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2018
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 17, 2017
CompletedFirst Posted
Study publicly available on registry
January 19, 2017
CompletedStudy Start
First participant enrolled
May 2, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
May 5, 2026
April 1, 2026
9.1 years
January 17, 2017
April 30, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Incidence of adverse events
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.
Up to 2 years
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)
The Bayesian modified toxicity probability interval method will be used to find the recommended dose.
Up to 28 days
Overall survival (OS) in patients treated with IT and IV nivolumab (dose expansion part)
Up to 2 years
Secondary Outcomes (2)
OS
Up to 2 years
Immunological effects of nivolumab
Up to 2 years
Study Arms (1)
Treatment (nivolumab)
EXPERIMENTALPatients receive nivolumab IT over 5 minutes on day 1 of every cycle. Beginning in cycle 2, patients also receive nivolumab 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 CT or PET at baseline, cycle 5 and then every 8 weeks. Patients undergo MRI at baseline, cycles 3, 5, and then every 8 weeks.
Interventions
Correlative studies
Undergo CT
Undergo lumbar puncture for cerebrospinal fluid collection
Undergo MRI of brain and spine
Given IV or IT
Undergo PET
Eligibility Criteria
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
- +23 more criteria
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
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Glitza Oliva IC, Ferguson SD, Bassett R Jr, Foster AP, John I, Hennegan TD, Rohlfs M, Richard J, Iqbal M, Dett T, Lacey C, Jackson N, Rodgers T, Phillips S, Duncan S, Haydu L, Lin R, Amaria RN, Wong MK, Diab A, Yee C, Patel SP, McQuade JL, Fischer GM, McCutcheon IE, O'Brien BJ, Tummala S, Debnam M, Guha-Thakurta N, Wargo JA, Carapeto FCL, Hudgens CW, Huse JT, Tetzlaff MT, Burton EM, Tawbi HA, Davies MA. Concurrent intrathecal and intravenous nivolumab in leptomeningeal disease: phase 1 trial interim results. Nat Med. 2023 Apr;29(4):898-905. doi: 10.1038/s41591-022-02170-x. Epub 2023 Mar 30.
PMID: 36997799DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Isabella C Glitza, MD
M.D. Anderson Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 17, 2017
First Posted
January 19, 2017
Study Start
May 2, 2018
Primary Completion (Estimated)
June 1, 2027
Study Completion (Estimated)
June 1, 2027
Last Updated
May 5, 2026
Record last verified: 2026-04