A Phase I Study of CCI-779 (Temsirolimus) in Combination With Topotecan in Patients With Gynecologic Malignancies

Inclusion Criteria:

Histologically confirmed recurrent or metastatic ovarian carcinoma, fallopian tube carcinoma, primary peritoneal carcinoma, cervical carcinoma, endometrial carcinoma, vulvar carcinoma, vaginal carcinoma, or carcinosarcoma of the ovary, endometrium or cervix.
Prior Therapy: at least one and may have up to three prior cytotoxic chemotherapeutic regimens for the management of primary disease.
Must be at least 18 years of age.
GOG performance status must be 0 or 1.

Patients must have adequate organ and marrow function as defined below:

hemoglobin ≥10g/dL
absolute neutrophil count ≥1,500/uL
platelets ≥100,000/uL
total bilirubin below the institutional upper limit of normal
AST(SGOT)/ALT(SGPT) below the institutional upper limit of normal
creatinine below the institutional upper limit of normal
cholesterol ≤ 350 mg/dL (fasting)
triglycerides ≤ 400 mg/dL (fasting)
albumin ≥ 3.0 mg/dL
negative pregnancy test for women able to have children
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Prior therapy with topotecan
More than 3 prior cytotoxic chemotherapeutic regimens or treatment with temsirolimus or any other mTOR inhibitor
Concomitant hormonal therapy or radiation therapy
Clinically significant infections or other medical problems of significant severity
History of unstable angina or myocardial infarction within the past six months
Known brain metastases unless the metastases have been controlled by prior surgery or radiotherapy, and the patient has been neurologically stable and off of steroids for at least 4 weeks.
Any requirement for oxygen
Cannot be receiving potent enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital) nor any other potent CYP3A4 inducer such as rifampin or St. John's wort, as these may decrease temsirolimus levels. Use of agents that potently inhibit CYP3A4 (and hence may raise temsirolimus levels), such as ketoconazole, is discouraged, but not specifically prohibited.