Phase II Study of RAD001 Head and Neck Cancer

Inclusion Criteria:

• Histologically or cytologically documented squamous cell CA of the head and neck
• Metastatic and/or recurrent head and neck cancer (not eligible for curative intent surgical or radiation therapy)
• Patients must have at least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
• Performance status 0-2
• Age ≥18 years
• Non-pregnant
• Prior treatment:
• Prior treatment for recurrent or metastatic disease required (at least one): up to but no more than 2 regimens (chemotherapy and/or biologic) allowed.
• Prior induction and concomitant chemoradiotherapy with a curative intent (with or without biologic agents) is allowed
• No other serious medical or psychiatric disease
• Required Lab Values:

Granulocytes ≥ 1,500/µl Platelets ≥ 100,000/µl Bilirubin ≤ 1.5 x ULN INR ≥ 1.3 (or < 3 if on anticoagulation) AST or ALT ≤ 2.5 x ULN (< 5 x ULN in patients with liver metastases) Creatinine ≤ ULN or Creatinine Clearance >= 60 mL/min, if creatinine above ULN

• Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
• Patients with accessible tumor tissue must agree to a pre-treatment biopsy at screening. If available, original diagnostic tissue may be submitted in place of the pre-treatment biopsy.
• Signed informed consent

Exclusion Criteria:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
• Prior treatment with any investigational drug within the preceding 4 weeks
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg. However, patients receiving corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with RAD001. 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
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Symptomatic congestive heart failure of New York heart Association Class III or IV
• unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
• severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air. PFTs as clinically indicated.
• uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
• active (acute or chronic) or uncontrolled severe infections
• liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• A known history of HIV seropositivity
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
• Patients with an active, bleeding diathesis
• 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 must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001)
• Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
• Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients
• Patients unwilling to or unable to comply with the protocol