Vorinostat and Hydroxychloroquine in Treating Patients with Advanced Solid Tumors

Inclusion Criteria

• Patients must have a histologically confirmed non-hematological malignancy established by biopsy or resection; patients must have received and failed standard treatment for their malignancy; patients for whom no standard treatment is available will also be eligible
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) at 0, 1, 2; (i.e. the patient must be able to care for himself/herself with only occasional help from others)
• 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 upper limits of the institutional norm; ALT, AST can be < 5 times upper limits of normal if patients have hepatic involvement
• Patients must be 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; a positive pregnancy test will prohibit the subject from receiving the investigational product
• Complete supportive and palliative care will continue to be provided to ameliorate signs and symptoms that were pre-existing or may arise while on study and which do not interfere with the objectives of the study
• Tumor blocks available from previous surgery/biopsy; at the tumor specific expansion, only patients with metastatic colorectal and renal cell cancers will be enrolled; patients with metastatic colorectal and renal cancer must have been treated and progressed or intolerant to standard care therapy; patients with colorectal cancer must have been treated in the past with irinotecan and/or oxaliplatin and/or avastin/EGFR therapy or intolerant to these agents; no more than 4 lines of therapy permitted in the metastatic setting; patients with colorectal cancer may enroll irrespective of K-Ras mutational status, although this will be documented; patients with renal cell cancer must have been treated with a VEGF targeted therapy and/or mTOR inhibitor; prior treatment with vorinostat and HCQ are not permitted in each tumor type

Exclusion Criteria

• Patients with uncontrolled brain metastases; patients with brain metastasis must be asymptomatic and off corticosteroid use 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 diabetic retinopathy
• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events to =< grade 1 due to agents administered more than 4 weeks earlier; 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 vorinostat 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
• Clinically significant hypercalcemia (including vomiting, dehydration and neurological symptoms)
• Corrected QT interval (QTc) > 500 ms at baseline (average of 3 determinations at 10 minutes interval)
• Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (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
• Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
• 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