Ridaforolimus in Treating Patients With Recurrent Metastatic and/or Locally Advanced Endometrial Cancer

DISEASE CHARACTERISTICS:

• Histologically confirmed endometrial cancer, including any 1 of the following subtypes:
• Adenocarcinoma
• Papillary serous
• Papillary
• Villoglandular
• Mucinous
• Clear cell
• Endometrioid
• Adenosquamous carcinoma
• Recurrent or metastatic and/or locally advanced disease
• Incurable disease by standard therapies
• Clinically and/or radiologically documented disease within the past 28 days (35 days if negative), defined as ≥ 1 unidimensionally measurable disease site meeting 1 of the following criteria:
• At least 20 mm by x-ray or physical exam
• At least 10 mm by spiral CT scan
• At least 20 mm by non-spiral CT scan
• Available tumor tissue (paraffin block or unstained slides) from primary tumor
• No uterine sarcoma (leiomyosarcoma), mixed müllerian tumor (MMT), and/or adenosarcoma
• No known brain metastases
• Clinical suspicion of CNS involvement requires a head CT scan

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN
• Creatinine ≤ 1.25 times ULN OR creatinine clearance ≥ 50 mL/min
• Fasting serum cholesterol ≤ 9.0 mmol/L
• Fasting triglycerides ≤ 4.56 mmol/L
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Accessible for treatment and follow up (e.g., 1 ½ hours driving distance from participating center)
• No upper gastrointestinal or other condition that would impair swallowing or absorption of oral medication
• No serious illness or medical condition that would not permit the patient to be managed according to the protocol, including, but not limited to, any of the following:
• History of significant neurologic or psychiatric disorder (e.g., uncontrolled psychotic disorders) that would impair the ability to obtain consent or limit compliance with study requirements
• Active uncontrolled or serious infection
• Active peptic ulcer disease
• Myocardial infarction within the past 6 months, congestive heart failure (even if medically controlled), unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, or uncontrolled hypertension
• Pulmonary disease requiring oxygen
• HIV infection or other immune deficiency
• Other medical conditions that might be aggravated by study treatment
• No history of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
• No known hypersensitivity to the study drug or its components

PRIOR CONCURRENT THERAPY:

• At least 7 days since prior hormonal therapy (progestational or aromatase inhibitor) as either adjuvant therapy or for treatment of metastatic disease
• At least 21 days since prior major surgery and recovered
• At least 28 days since prior radiotherapy and recovered
• Prior low-dose palliative radiotherapy allowed
• At least 4 months since prior adjuvant chemotherapy
• No prior mTOR inhibitors
• No prior or concurrent chemotherapy for metastatic or recurrent disease
• More than 7 days since prior and no concurrent CYP3A4 inhibitors including, but not limited to, any of the following:
• Azole antifungals (i.e., ketoconazole, itraconazole, miconazole, fluconazole)
• HIV protease inhibitors (i.e., indinavir, saquinavir, ritonavir, atazanavir, nelfinavir)
• Clarithromycin
• Verapamil
• Erythromycin
• Delavirdine
• Diltiazem
• Nefazodone
• Telithromycin
• More than 12 days since prior and no concurrent CYP3A4 inducers including, but not limited to, any of the following:
• Rifampin
• Phenytoin
• Rifabutin
• St. John's wort
• Carbamazepine
• Efavirenz
• Phenobarbital
• Tipranavir
• At least 14 days since prior and no concurrent investigational drugs or anticancer therapy (e.g., immunotherapy, biological response modifiers [excluding hematopoietic growth factors], and systemic hormonal therapy)
• No concurrent CYP3A4 substrates