Guadecitabine and Nivolumab in Treating Refractory Metastatic Colorectal Cancer

Exclusion Criteria

• •Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study (or within 6 weeks for nitrosurea or mitomycin C) or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• •Patients may not be receiving any other investigational agents
• •Any previous treatment with a hypomethylating agent, or with an anti-PD1 or anti-PD-L1 or anti-PD-L2 or anti-CTLA-4 inhibitor, including nivolumab (or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Any immunomodulatory agent that is not described above should be cleared by the principal investigator (PI)
• •Known hypersensitivity to any of the components of guadecitabine or nivolumab
• •Receipt of live attenuated vaccination within 30 days prior to study entry
• •History of leptomeningeal carcinomatosis or uncontrolled seizures
• •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
• •Malignancies other than colorectal adenocarcinoma within 5 years prior to treatment, except for adequately treated carcinoma in situ (e.g. of the cervix), non-melanoma skin cancer, T1a or T1b prostate cancer treated with curative intent at least 1 year prior to study entry with normal prostate specific antigen (PSA), and ductal carcinoma in situ treated surgically with curative intent. Other early stage cancers that have a minimal chance of recurrence (i.e. stage I endometrial cancer, cervical cancer, etc.) may be cleared and should be discussed with the PI
• •Renal insufficiency requiring dialysis
• •Known positivity for human immunodeficiency virus (HIV)
• •Active hepatitis B, hepatitis C
• •Surgery (including open biopsy), significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during study treatment
• •Active or prior documented autoimmune disease. Subjects with vitiligo, Graves disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
• •Active or prior documented inflammatory bowel disease (e.g., Crohn?s disease, ulcerative colitis)
• •History of allogeneic organ transplant
• •Current or prior use of immunosuppressive medication within 28 days before the first dose of nivolumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Live attenuated vaccines within 30 days of nivolumab dosing (i.e. 30 days prior to the first dose, during treatment with nivolumab and for 30 days post discontinuation of nivolumab. Inactivated vaccines, such as the injectable influenza vaccine, are permitted
• •Known history or ongoing diagnosis of pneumonitis
• •Known history of previous clinical diagnosis of tuberculosis
• •Mean QT interval corrected for heart rate (QTc) \>= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia?s correction
• •Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants