A Phase I Study of the Weekly Oral RAD001 in Combination With Oral Topotecan in Patients With Advanced or Recurrent Endometrial Cancers

Inclusion Criteria:

- Patients must have histologically-confirmed advanced or recurrent endometrial cancer

- Patients must be refractory to standard therapy or for which no curative standard
therapy exists, to be considered. Metastatic disease, if present, should not be
progressing so as to require palliative treatment within 4 weeks of enrollment based
on clinical assessment by the investigator.

- Development of new lesions or an increase in preexisting lesions on bone
scintigraphy, CT, MRI or by physical examination. Patients in whom the sole
criterion for progression is an increase in a biochemical marker, e.g.,
carcinoembryonic antigen (CEA), or an increase in symptoms, are not eligible.

- Age ≥ 18 years

- WHO performance status ≤ 2

- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x
109/L, Hb >9 g/dL

- Adequate liver function as shown by:

- serum bilirubin ≤ 1.5 x ULN

- INR < 1.3 (or < 3 on anticoagulants)

- ALT and AST ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases)

- Adequate renal function: serum creatinine ≤ 1.5 x mg/dL

- 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.

- 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

- 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

- History of noncompliance to medical regimens

- Patients unwilling to or unable to comply with the protocol