Everolimus in Treating Patients With Relapsed or Metastatic Endometrial Cancer

RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well everolimus works in treating patients with relapsed or metastatic endometrial cancer.

OBJECTIVES:

Primary

* Estimate the rate of non-progression after 3 months of treatment with everolimus in patients with relapsed or metastatic endometrial cancer.

Secondary

* Evaluate the partial and complete response rate after 3 months of treatment with everolimus in these patients.
* Evaluate the duration of response in these patients.
* Evaluate the clinical benefit after 6 months of treatment with everolimus in these patients.
* Evaluate the time to progression in these patients.
* Evaluate the progression-free and overall survival of these patients.
* Evaluate the nature, frequency, and severity of side effects of everolimus in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral everolimus daily in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed monthly for 3 months and then every 3 months thereafter.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed adenocarcinoma of the endometrium

  * Metastatic disease after first- or second-line chemotherapy
* Previously treated with platinum-based therapy in the adjuvant or metastatic setting
* Must have ≥ 1 measurable metastatic lesion outside previously irradiated areas
* No locally recurrent resectable tumor
* No uncontrolled brain metastases

PATIENT CHARACTERISTICS:

* WHO performance status 0-1
* ANC ≥ 1,000/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 9 g/dL
* Transaminases ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN in the presence of liver metastases)
* Alkaline phosphatase ≤ 2.5 times ULN
* Bilirubin ≤ 1.5 times ULN
* Creatinine clearance ≥ 50 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other cancer within the past 3 years except for curatively treated carcinoma in situ of the cervix or basal cell or squamous cell skin carcinoma
* No concurrent serious and/or uncontrolled disease that would preclude study participation, including any of the following:

  * Uncontrolled diabetes
  * Uncontrolled hypertension
  * Severe infection
  * Profound malnutrition
  * Unstable angina
  * NYHA class III-IV congestive heart failure
  * Ventricular arrhythmia
  * Coronary artery disease
  * Myocardial infarction within the past 6 months
  * Liver disease
  * Chronic renal failure
  * Progressive ulceration of the upper gastrointestinal tract
* No hypersensitivity to everolimus, sirolimus, or lactose
* No abnormalities ≥ grade 3
* No psychological, familial, social, or geographical reasons that would preclude study follow-up
* No history of poor compliance to medical treatment

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior experimental drugs (e.g., mTOR inhibitors)
* More than 21 days since prior and no other concurrent chemotherapy, hormonal therapy, or antitumor therapy
* More than 5 days since prior strong CYP3A4 inhibitors or inducers (e.g., rifabutin, rifampicin, clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir, or telithromycin)
* More than 30 days since other prior treatments
* No concurrent participation in another clinical trial that would interfere with the objectives of this study
* No concurrent anticoagulation, except for 1 mg of coumadin per day or low molecular weight heparin