Sorafenib Tosylate and Everolimus in Treating Patients With Advanced Solid Tumors and Metastatic Pancreatic Cancer That Does Not Respond to Gemcitabine Hydrochloride

Exclusion Criteria

• •Phase II: Patients in whom histological or cryological diagnosis is not consistent with adenocarcinoma including adenosquamous, islet cell, cystoadenoma or cystadenocarcinoma, carcinoid, small or large cell carcinoma or lymphoma
• •Phase II: Adenocarcinoma arising from a site other than the pancreas (distal bile duct, ampulla of vater or periampullary duodenum)
• •Prior therapy with approved or investigational agents within 4 weeks prior to the start of treatment plan in this protocol
• •Uncontrolled diabetes as defined by fasting serum glucose \> 1.5 x ULN
• •Any active infections
• •Cardiac disease: Congestive heart failure \> class II New York Heart Association (NYHA); patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
• •Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• •Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management
• •Cerebrovascular accident including transient ischemic attacks within the past 6 months
• •Pulmonary hemorrhage/bleeding event \>= Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 within 4 weeks of first dose of study drug
• •Any other hemorrhage/bleeding event \>= CTCAE Grade 3 within 4 weeks of first dose of study drug
• •Serious non-healing wound, ulcer, or bone fracture
• •Known or suspected allergy to sorafenib, everolimus, other rapamycins (sirolimus, temsirolimus), their excipients, or any agent given in the course of this trial
• •Any condition that impairs patient's ability to swallow whole pills
• •Any malabsorption problem
• •Presence of central nervous system or brain metastases
• •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days of first study drug
• •Urine protein:creatinine ratio \>=1.0 at screening
• •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of baseline
• •Inability to comply with study and/or follow-up procedures
• •History of concurrent malignancy or history of a second malignancy within the past 5 years
• •Unable to provide informed consent
• •Concomitant use of any medications or substances that are inhibitors or inducers of CYP3A enzyme, which include but not limited to phenytoin, carbamazepine, barbiturates, rifampin, Phenobarbital or St. Johns Wort
• •Phase II: Prior treatment with mTOR inhibitors (e.g., sirolimus, temsirolimus, everolimus) or Ras-MAPK inhibitors (e.g., sorafenib)
• •Any unresolved chronic toxicity greater than CTCAE grade 2 from previous anticancer therapy (except alopecia)
• •Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent; topical or inhaled corticosteroids are allowed
• •Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period; close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus (Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines)
• •Severely impaired lung function as defined as spirometry and diffusing capacity of carbon monoxide (DLCO) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air; patients are not required to undergo mandatory respiratory function tests at screening to be eligible unless medically necessary
• •Severe and/or uncontrolled non-malignant liver disease such as cirrhosis or severe hepatic impairment defined as Child-Pugh class C
• •A known history of human immunodeficiency virus (HIV) seropositivity
• •Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods; if barrier contraceptives are being used, these must be continued throughout the trial by both sexes; hormonal contraceptives are not acceptable as a sole method of contraception
• •Women of childbearing potential (WOCBP) that have a positive urine or serum pregnancy test within 7 days prior to the start of treatment
• •Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception during the study and for 8 weeks after the end of treatment