This phase I trial studies the side effects and best dose of vandetanib and everolimus when given together in treating patients with cancer that has spread to other places in the body. Vandetanib and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) or highest dose level, and the dose-limiting toxicity (DLT) of vandetanib (a multi-kinase inhibitor of epidermal growth factor receptor [EGFR], vascular endothelial growth factor receptor [VEGFR] and ret proto-oncogene [RET] inhibitor) when used in combination with everolimus (a mammalian target of rapamycin [mTOR] inhibitor) in advanced cancer.

II. Preliminary descriptive assessment of the anti-tumor efficacy of the combination.

III. Preliminary optional assessment of the pharmacokinetic, pharmacodynamic markers of target inhibition and correlates of response.

OUTLINE: This is a dose-escalation study.

Patients receive vandetanib orally (PO) once daily (QD) and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment patients are followed up between 14-28 days at the discretion of the treating physician.

Inclusion Criteria:

• Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
• Patients must be at least 3 weeks beyond their previous cytotoxic chemotherapy.
• Patient must be at least 5 half-lives or 3 weeks, whichever is shorter, from their previous targeted or biologic therapy; In addition, patients must be at least 3 weeks beyond the last session of radiation therapy. Local palliative radiation therapy that is not delivered to all target lesions is allowed immediately before or during treatment.
• ECOG performance status should be less or equal to 3
• Patients must have organ and marrow function defined as: Absolute neutrophil count more or equal to 750/mL; platelets more or equal to 50,000/mL; creatinine less or equal to 3x ULN; total bilirubin less than or equal to 3.0.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence).

Exclusion Criteria:

• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
• Pregnant or lactating women.
• History of hypersensitivity to vandetanib, lactose, murine products, or any component of the formulation.
• History of hypersensitivity to sirolimus, temsirolimus, everolimus.
• History of hypersensitivity to any component of the formulation.
• Patients unwilling or unable to sign informed consent document.
• Presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
• History (within the last 3 months) or presence of stroke/cerebrovascular accident.
• Congenital long QT syndrome.
• QTcF interval greater than 500 ms that is not correctable to less than 500ms such as with cessation of a causative medication, etc.
• History of myocardial infarction within 6 months with a residual arrhythmia that in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
• Presence of a symptomatic bradyarrhthmia or uncompensated heart failure.