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

Inclusion Criteria

• •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