RAD001 in Recurrent Endometrial Cancer Patients
Condition: Endometrial Cancer
MeSH terms: Endometrial Neoplasms
Intervention: RAD001
Intervention description: 10 mg by mouth Daily
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: Female
Healthy volunteers: No
Keywords: Recurrent Endometrial Cancer; Endometrial; Endometrioid; RAD001; Uterine Cancer

Summary:

      The goal of this clinical research study is to learn if RAD001 can shrink or slow the growth
      of tumors in patients who have recurrent endometrial cancer. The safety of this drug will
      also be studied.

      Objectives:

      Primary Objective:

      1. To determine the efficacy of RAD001 in patients with progressive or recurrent endometrial
      cancer.

      Secondary Objective:

        1. To determine the nature and degree of toxicity of RAD001 in this cohort of patients.

        2. To characterize, in pre- and post- treatment tumor samples, when available, expression
           levels of total and phosphorylated mTOR (mammalian "target of rapamycin") as well as
           relevant upstream and downstream signaling components (optional).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed progressive or recurrent endometrial cancer (endometrioid or
             mixed with endometrioid component histology; any grade).

          2. Patients may have failed no more than two prior chemotherapies for the recurrent
             disease (does not include chemosensitizing radiation).

          3. All patients must have measurable disease. Measurable disease is defined as lesions
             that can be measured by physical examination or by means of imaging techniques.
             Ascites and pleural effusions are not considered measurable disease.

          4. Patients must have a pretreatment granulocyte count (i.e., segmented neutrophils +
             bands) of >/=1,500/Fl, a hemoglobin level of >/=9.0 gm/dL and a platelet count of
             >/=100,000/Fl.

          5. Patients must have an adequate renal function as documented by serum creatinine </=2.0
             mg/dL.

          6. Patients must have adequate hepatic function as documented by a serum bilirubin </=1.5
             mg/dL, regardless of whether patients have liver involvement secondary to tumor.
             Aspartate transaminase (SGOT) must be </=3x institutional upper limit of normal unless
             the liver is involved with tumor, in that case the aspartate transaminase must be
             </=5x institutional upper limit of normal.

          7. Patients must have a Zubrod performance status of 0, 1, or 2.

          8. Patients must have signed an approved informed consent.

        Exclusion Criteria:

          1. Patients who have previously received RAD001 or another mammalian target of rapamycin
             (mTOR) inhibitor.

          2. Patients whose tumors have serous carcinomas, mixed malignant mullerian tumors (MMMT)
             components or uterine sarcomas.

          3. Patients who have isolated recurrences (vaginal, pelvic, or para-aortic) that are
             amenable to potentially curative treatment with radiation therapy or surgery.

          4. Patients with a history of psychiatric disorders that would interfere with consent or
             follow-up.

          5. Patients with a history of myocardial infarction within the previous six months or
             congestive heart failure requiring therapy.

          6. Patients with a history of prior malignancy (except for adequately treated basal cell
             or squamous cell skin cancer, in situ cervical cancer) or other cancer for which the
             patient has been disease-free for at least five years.

          7. Pregnant or lactating women. Women of reproductive potential may not participate
             unless they have agreed to use an effective contraceptive method.

          8. Patients with a history of seizures are ineligible. Patients receiving phenytoin,
             phenobarbital, or other anti-epileptic prophylaxis are ineligible.

          9. Patients with any other severe concurrent disease which would make the patient
             inappropriate for entry into this study, including significant hepatic, renal, or
             gastrointestinal diseases.

         10. Patients with deep venous or arterial thrombosis (including pulmonary embolism) within
             6 weeks of study entry.

         11. Patients with >/= grade 2 hypercholesterolemia or hypertriglyceridaemia (fasting
             state), despite lipid lowering therapy should be excluded from entering the study.

         12. Patients currently taking any of the medications listed in Appendix A (Patients will
             be given a listing of these medications at the time of the informed consent).

         13. Known hypersensitivity to everolimus, sirolimus or excipients including
             hydroxytoluene, magnesium stearate, hydroxypropylmethyl-cellulose, crospovidone and
             lactulose.