Phase II Trial of RAD001 (Everolimus) in Previously Treated Small Cell Lung Cancer
Condition: Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: RAD001 (everolimus)
Intervention description: 10 mg by mouth daily without interruption for 3-week cycles until disease progression or intolerable toxicities
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: small cell; lung

Summary:

      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. RAD001 will be
      administered orally at a dose of 10 mg daily.
    

Eligibility criteria:

        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.