Ipilimumab and Nivolumab in Treating Patients with Solid Tumors with Leptomeningeal Metastases

Inclusion Criteria

• Participants must have histologically or cytologically confirmed disease from any solid tumor
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy of greater than 3 weeks
• Absolute neutrophil count (ANC) >= 1500/mcL (performed within 14 days of treatment initiation)
• Platelets >= 100,000/mcL (performed within 14 days of treatment initiation)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 14 days of treatment initiation)
• Serum creatinine OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) =< serum creatinine =< 1.5 x upper limit of normal (ULN) or creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft-Gault formula) (performed within 14 days of treatment initiation) * Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 14 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 ULN OR =< 5 X ULN for subjects with liver metastases (performed within 14 days of treatment initiation)
• Albumin >= 2.5 mg/dL (performed within 14 days of treatment initiation)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 14 days of treatment initiation)
• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 14 days of treatment initiation)
• Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception; 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
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to the start of nivolumab
• 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; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; women who are not of childbearing potential, ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception
• Ability to understand and the willingness to sign a written informed consent document
• Stable dose of dexamethasone 2 mg or less for 7 days prior to initiation of treatment
• Carcinomatous meningitis, as defined by positive cytology or biopsy; if cerebrospinal fluid (CSF) cytology is negative, but imaging is consistent with carcinomatous meningitis, patient is eligible

Exclusion Criteria

• Participants who have had chemotherapy, targeted small molecule therapy or study therapy within 5 days of protocol treatment, or those who have not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier; subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study; if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Participants who are receiving any other investigational agents
• Patients should be excluded if they have an active, known or suspected autoimmune disease; subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; subjects are permitted to use topical, ocular, intraarticular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted
• Drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen
• Patients should be excluded if they have had prior systemic treatment with an anti-CTLA4 antibody and anti-PD1/PDL1 antibody; prior treatment with single agent anti-CTLA4, anti-PD1 or anti-PDL1 antibody is allowed
• Has a known history of active TB (Bacillus tuberculosis)
• Patients should be excluded if they are positive test for hepatitis B virus surface antigen (hepatitis B virus [HBV] surface antigen [sAg]) or hepatitis C virus ribonucleic acid (hepatitis C virus [HCV] antibody) indicating acute or chronic infection
• Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS); these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has received a live vaccine within 30 days of planned start of study therapy; Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
• History of allergy to study drug components
• History of severe hypersensitivity reaction to any monoclonal antibody