This research study is studying a combination of two drugs as a possible treatment for Leptomeningeal Metastases. The names of the study interventions involved in this study are: * Ipilimumab * Nivolumab
This research study is a Phase II clinical trial. Researchers hope to study the effects of the combination of Nivolumab and Ipilimumab. Many cancers use specific pathways, such as programmed death-1 (PD-1), programmed death-ligand-1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4), to evade the body's immune system. Nivolumab and ipilimumab work by blocking the PD-1/PD-L1 and CTLA-4 pathways and thus releasing the brakes on the immune system so it can stop or slow cancer. The FDA (the U.S. Food and Drug Administration) has approved Nivolumab and Ipilimumab as a treatment option for melanoma, but has not approved them for use when cancer cells spread to the cerebrospinal fluid
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
* Melanoma: \- Combination therapy with Nivolumab 1 mg/kg for 4 doses followed by monotherapy Nivolumab 480 mg per cycle. * Non-small Cell Lung Cancer / Head and Neck Cancer: \- Combination therapy with Nivolumab 3 mg/kg * Small Cell Lung Cancer / Breast Cancer / Bladder Cancer: \- Combination therapy with Nivolumab 1 mg/kg for 4 doses followed by monotherapy Nivolumab 240 mg per cycle. * Renal Cell Carcinoma / Other Solid Tumors (not listed above): * Combination therapy with Nivolumab 3 mg/kg for 4 doses followed by monotherapy Nivolumab 480 mg per cycle.
* Non-small Cell Lung Cancer / Head and Neck Cancer: \- Combination therapy with Ipilimumab 1 mg/kg * Small Cell Lung Cancer / Breast Cancer / Bladder Cancer: \- Combination therapy with Ipilimumab 3 mg/kg for 4 doses * Renal Cell Carcinoma / Other Solid Tumors (not listed above): * Combination therapy with Ipilimumab 3 mg/kg for 4 doses
Massachusetts general Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Percentage of Participants With Overall Survival
Overall Survival (OS) is defined as the time from registration to death due to any cause, or censored at date last known alive.
Time frame: 3 months
Percentage of Participants With Treatment-related Adverse Events
Grade 3 or 4 treatment-related adverse events occurring in at least 15% of participants, based on CTCAE v4.0 criteria.
Time frame: 2 years
Cumulative Incidence of Progressive Disease at 3 Months for Intracranial Sites
Cumulative incidence describes the average probability of developing progressive disease (PD) by immunotherapy response assessment for neuro-oncology (iRANO) criteria. PD is defined as any of the following: (1) \>/= 25% increase in 2-dimensional contrast lesions; (2) significant worsened changes on T2-weighted MRI scans; (3) new lesion; or (4) significant clinical decline. Confirmation of progressive disease is based on follow-up imaging for participants without significant clinical decline.
Time frame: 3 months post-treatment
Cumulative Incidence of Progressive Disease at 3 Months for Extracranial Sites
Cumulative incidence describes the average probability of developing progressive disease (PD) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. PD is defined as any of the following: (1) \>/= 25% increase in 2-dimensional contrast lesions; (2) significant worsened changes on T2-weighted MRI scans; (3) new lesion; or (4) significant clinical decline. Confirmation of progressive disease is based on follow-up imaging for participants without significant clinical decline.
Time frame: 3 months post-treatment
Number of Participants With Leptomeningeal Disease (LMD) Response Post-Treatment
Cerebrospinal fluid (CSF) collection and cytology is done 6-9 weeks after treatment initiation to assess for LMD response, especially complete response or partial response. Complete Response is defined as: * Reversion to negative CSF cytology (or NA) * Disappearance of all disease related symptoms present prior to therapy (or NA) * Complete disappearance of all detectable radiographic evidence of disease (or NA). Partial Response is defined as: * \> 50% decrease in malignant CSF cytology * Improvement in neurologic symptoms or no worsening of symptoms * Improvement in radiographic evidence of disease. No new sites of measurable or assessable central nervous system (CNS) disease.
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Time frame: 6-9 weeks after treatment initiation
Extracranial Progression-Free Survival
Extracranial Progression-Free Survival (EPFS) is defined as the time from first dose of study drug to documented extracranial disease progression or death, whichever occurs first. Extracranial disease progression is assessed with CT scans of the chest, abdomen, and pelvis, by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria and immune-related response criteria (irRC) criteria. Progression is defined using RECIST v1.0 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The follow-up of participants who have neither died nor progressed at the time of analysis will be censored at the date of last adequate disease assessment.
Time frame: 2 years
Intracranial Progression-Free Survival
Intracranial Progression-Free Survival (IPFS) is defined as the time from first dose of study drug to documented intracranial disease progression or death, whichever occurs first. Intracranial disease progression is assessed with CT or MRI scans of the brain, using the Response assessment in neuro-oncology (RANO) criteria, which defines progression as: * ≥ 25% increase in in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline; or * Presence of new lesions; or * Worsening of clinical/neurologic status (unless clearly unrelated to the cancer); or * Worsening of non-measurable disease. The follow-up of participants who have neither died nor progressed at the time of analysis will be censored at the date of last adequate disease assessment.
Time frame: 2 years