Phase II Trial of RAD001 (Everolimus) in Previously Treated Small Cell Lung Cancer

This is a phase II, two-stage, open-label, single-agent study of the experimental drug RAD001
(everolimus) in patients with previously treated small cell lung cancer. Patients may have
received up to 2 prior chemotherapy regimens for small cell lung carcinoma, but no prior
therapy with an m-TOR inhibitor. RAD001 will be administered orally at a dose of 10 mg daily.
A cycle will be defined as 3 weeks of study drug administration, and patients will have tumor
measurements every 2 cycles. Study participation will continue until disease progression or
intolerable toxicities. In addition, in patients who consent, archival tumor tissue (paraffin
block from original biopsy) will be collected for research purposes.

Inclusion Criteria:

1. Cytologically or histologically confirmed small cell carcinoma of the lung that has
progressed post first-line therapy. Mixed small and non-small cell tumors are
excluded.

2. Prior chemotherapy for small cell carcinoma. Up to 2 prior chemotherapy regimens for
small cell lung carcinoma are allowed. No prior therapy with an m-TOR inhibitor (e.g.
CCI-779).

3. Unidimensionally measurable disease (RECIST criteria). If the only site of measurable
disease is in a previously irradiated area, the patient must have documented
progression of disease in this area.

4. ECOG performance status 0-2.

5. A minimum of 4 weeks should elapse from prior chemotherapy. Patients must have fully
recovered from the effects of any prior surgery or radiation therapy or other
anticancer therapies, including immunotherapy and investigational agents.

6. No progressive brain metastases. Brain metastases should have been previously treated
with surgery and/or radiation.

7. Patients with a prior malignancy should have at least 3 years of disease-free
survival. Prior curatively treated squamous cell or basal carcinoma of the skin or in
situ cervical cancer or other in situ malignancies are allowed.

8. No other coexisting medical condition that would preclude full compliance with the
study.

9. Required laboratory values (obtained < 1 week prior to enrollment):

- ANC >/= 1500/mm³

- Platelets >/= 100,000/mm³

- AST and ALT ≤ 3 x ULN (upper limits of normal). In patients with liver metastases
AST and ALT should be < 5 x ULN.

- Total bilirubin up to 1.5 x ULN (upper limits of normal).

10. Age >/= 18 years and capacity to give informed consent.

11. Patients should be advised to discontinue drugs that interact with CYP3A4 (see list of
examples in Table 3.1 of the full protocol), if medically safe.

12. All patients must have given signed, informed consent prior to registration on study.

Exclusion Criteria:

1. Prior treatment with any investigational agent within the preceding 4 weeks.

2. Other concurrent severe and/or uncontrolled medical disease which could compromise
participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension,
severe infection, severe malnutrition, unstable angina, or congestive heart failure -
New York Heart Association Class III or IV, ventricular arrhythmias active ischemic
heart disease, myocardial infarction within six months, chronic liver or renal
disease, active upper GI tract ulceration).

3. A known history of HIV seropositivity.

4. 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).

5. Patients with an active, bleeding diathesis or on anticoagulation (except low dose
warfarin).

6. Pregnant and lactating women are excluded from the study because the agents used in
this study may be teratogenic to a fetus and there is no information on the excretion
of the agents or their metabolites into breast milk.

7. Women of childbearing potential and sexually active males must agree to use an
accepted and effective method of contraception (hormonal or barrier methods,
abstinence) prior to study entry and for the duration of the study.

8. Patients should not be on chronic systemic glucocorticoids or other immunosuppressant.