Autophagy Therapeutics (Hydroxychloroquine, Nelfinavir, Metformin, Dasatinib, and Sirolimus) for the Treatment of Advanced Solid Tumors or Relapsed Prostate Cancer

Inclusion Criteria

• Patient must have advanced solid tumor cancer of any type (Phase I) or advanced prostate cancer (Phase II)
• Tissue diagnosis documented by pathology report, or clinic note attesting to same
• Measurable/evaluable tumor by Response Evaluation Criteria in Solid Tumors (RECIST), quantitative blood biomarker, or radionuclide imaging
• Voluntary, signed and dated, Institutional Review Board (IRB) approved consent form in accordance with regulatory and institutional guidelines
• Documented progression of disease during treatment with one or more standard systemic regimens. Single or multiple regimens of chemotherapy, hormone suppression therapy, radiation therapy, surgery, immunotherapy, or adoptive cell therapy are allowed
• 18 years of age or older
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Bilirubin =< 1.5 times upper limit of normal (ULN). Subjects with Gilbert’s syndrome may be included if the total bilirubin is < 3 times ULN and the direct bilirubin is within normal limits
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 times ULN
• Serum creatinine =< 1.5 time ULN AND
• Creatinine clearance (CrCl) >= 50 mL/min for male patients or >= 45 mL/min for female patients, according to Cockcroft-Gault formula
• Absolute neutrophil count (ANC) >= 1,000 cells/mm^3
• Platelet count >= 75,000 cells/mm^3
• Hemoglobin >= 9 g/ dL
• Fasting glucose =< 160 mg/dL or non-fasting glucose =< 200 mg/dL
• Urinalysis with no clinically significant abnormalities
• Adequately controlled blood pressure as determined by the treating investigator
• Subjects with the potential to produce children must agree to effective contraceptive method use during study participation
• Patients requiring narcotic analgesics must be on stable doses for at least 2 weeks prior to study entry
• Patients being considered for a dose level containing nelfinavir mesylate must discontinue any statin use within 48 hours of beginning study treatment

Exclusion Criteria

• New York Heart Association class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or history of ischemia on electrocardiogram (ECG)
• Underlying psychiatric disorder requiring hospitalization within the last two years
• Clinically significant neurological disorder (Parkinson’s disease, dementia, multiple sclerosis), as determined by the enrolling investigator
• Active, uncontrolled bacterial, viral, or fungal infection, requiring systemic therapy
• Treatment with local or systemic radiation therapy, surgery, or investigational therapy within 28 days prior to registration
• Unwillingness or inability to comply with procedures required in this protocol
• Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator
• Patients who are receiving, coumadin, apixaban, argatroban or rivaroxaban
• Patients who are currently participating in any other clinical trial of an investigational product
• Any other mental incapacitation or psychiatric illness that would preclude study participation, as determined by the enrolling investigator
• Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
• Female patients who are of child-bearing potential (WOCBP) who are pregnant or planning to become pregnant during the study or within 6 months of last dose of study drugs. A urine pregnancy test for WOCBP will be collected during the screening period. Females will be determined to be not of child-bearing potential with a history of hysterectomy, tubal ligation, or age 45 or older with postmenopausal status > 12 months