Phase II Study of RAD001 Head and Neck Cancer
Condition: Squamous Cell Carcinoma of the Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Everolimus 10mg daily
Intervention description: RAD001 is a pill that will be taken orally (by mouth), at a dose of 10 mg, once a day for 28 days.
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: RAD001; Everolimus

Summary:

      To carry out exploratory studies to determine if activity of this regimen correlates with
      tumor and patient associated markers of the EGF-R/mTOR pathway These markers may correlate
      with activity of this regimen and provide exploratory insights in to the mechanism of this
      treatment approach.

      Expression of the pathway components including EGF-R and phosphorylated EGF-R (p-EGF-R), ERK
      and p-ERK, Akt and p-Akt(T308 and S473), p70s6k and p-p70s6k, S6 and p-S6, HIF-1-alpha, p27
      and 4E-BP1 will be assessed. Mutation and FISH analysis for EGF-R expression will also be
      performed on tumor samples. Biopsies will be obtained at the following times: pre-treatment,
      and after 4 weeks (one cycle) of treatment. If available, original diagnostic tissue may be
      submitted in place of the pre-treatment biopsy.
    

Eligibility criteria:

        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