Everolimus in Treating Patients With Relapsed or Metastatic Endometrial Cancer

Phase II Multicenter Study Evaluating the Tolerability and Efficacy of RAD001 (Everolimus) in 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.

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