Vorinostat and Hydroxychloroquine or Regorafenib in Treating Patients with Refractory Metastatic Colorectal Cancer

Inclusion Criteria

• Histological documentation of mCRC
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Radiographical documentation of metastatic disease with imaging up to 6 weeks prior to enrollment
• Patients with mCRC must have been previously treated with irinotecan and/or oxaliplatin and/or vascular endothelial growth factor (VEGF)/epidermal growth factor receptor (EGFR) therapy or intolerant to these agents
• Documentation of Kirsten rat sarcoma viral oncogene homolog (K-Ras) mutational status
• Absolute neutrophil count > 1000/mm^3
• Platelets > 75,000/mm^3
• Creatinine < 2 times the upper limits of normal (ULN)
• Total bilirubin < 1.5 mg/dl
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 times above the ULN, ALT and AST can be < 5 times ULN if patients have hepatic involvement
• Able to provide written informed consent
• Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; women of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the investigational product
• Tumor blocks available from previous surgery/biopsy, or if not available, patients willing to have biopsy

Exclusion Criteria

• Patients receiving prior therapy with RGF, VOR, and/or HCQ
• Patients with uncontrolled brain metastases; patients with brain metastases must be asymptomatic and off corticosteroids for at least one week
• Patients with porphyria are not eligible
• Patients with psoriasis are ineligible unless the disease is well controlled, and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations
• Patients with previously documented macular degeneration or untreated diabetic retinopathy (stable retinopathy is allowed)
• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; for investigational targeted therapies, patients will need to clear for 5 half-lives (not applicable to standard of care therapies)
• Patients may not be receiving any other investigational agents
• Patients should not have taken valproic acid or another histone deacetylase inhibitor for at least 2 weeks prior to enrollment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to VOR or HCQ
• 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
• Major surgery or significant traumatic injury occurring within 21 days prior to treatment
• Corrected QT interval (QTc) > 500 ms at baseline
• Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease; patients with nasojejunal (NJ), jejunostomy (J) or gastrostomy (G) tube will not be allowed to participate
• Pregnant women are excluded from this study; women of childbearing potential and men must also agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation
• Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; breastfeeding should be discontinued
• Informed consent - no study specific procedures will be performed without a written and signed informed consent document; patients who do not demonstrate the ability to understand or the willingness to sign the written informed consent document will be excluded from study entry