A Phase II Evaluation of Temsirolimus (CCI-779) (NCI Supplied Agent: NSC# 683864, IND# 61010) in Combination With Carboplatin and Paclitaxel Followed by Temsirolimus (CCI-779) Consolidation as First-Line Therapy in the Treatment of Stage III-IV Clear Cell Carcinoma of the Ovary

Inclusion Criteria:

- Diagnosis of stage III or IV clear cell ovarian cancer

- Primary tumors must be ≥ 50% clear cell histomorphology*

- No primary peritoneal or fallopian tube carcinoma

- Negative for the expression of WT-1 antigen and estrogen receptor (ER) antigen by
IHC**

- Newly diagnosed disease

- Undergone initial surgery for the combined purpose of diagnosis, staging, and
cytoreduction within the past 2-12 weeks

- GOG performance status 0-2

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Total bilirubin normal

- AST ≤ 2.5 times upper limit of normal (ULN) (< 5 times ULN for patients with liver
metastases)

- Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN for patients with liver
metastases)

- Creatinine ≤ 1.5 times ULN

- Cholesterol ≤ 350 mg/dL (fasting)

- Triglycerides ≤ 400 mg/dL (fasting)

- Albumin ≥ 3.0 mg/dL

- PT such that INR is ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient
is on a stable dose of therapeutic warfarin for management of venous thrombosis
including pulmonary thrombo-embolus)

- PTT < 1.2 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study treatment

- Neurologic function (sensory and motor) ≤ CTCAE grade 1

- No severely impaired lung function, defined as a DLCO ≤ 50% of the normal predicted
value and/or oxygen saturation ≤ 88% at rest on room air

- No baseline requirement for oxygen

- None of the following:

- NYHA class III-IV symptomatic congestive heart failure

- Unstable angina pectoris

- Myocardial infarction within the past 6 months

- Serious uncontrolled cardiac arrhythmia

- Any other clinically significant disease

- No poorly controlled diabetes

- No active infection requiring antibiotics (except for uncomplicated urinary tract
infection)

- No active bleeding or pathologic conditions that carry high risk of bleeding, such as
known bleeding disorder, coagulopathy, or tumor involving major vessels

- No other invasive malignancies within the past 5 years except for nonmelanoma skin
cancer

- No other serious concurrent illness that, in the opinion of the treating physician,
will place the patient at unreasonable risk from study treatment

- No concurrent live vaccines

- No prior cancer treatment that contraindicates study therapy

- No prior treatment with a mTOR inhibitor (sirolimus, temsirolimus, everolimus),
paclitaxel, or carboplatin

- No prior radiotherapy to any portion of the abdominal cavity or the pelvis

- Prior radiotherapy for localized cancer of the breast, head and neck, or skin is
allowed provided that it was completed ≥ 5 years before registration and the
patient remains free of recurrent or metastatic disease

- No prior chemotherapy for any abdominal or pelvic tumor, including neoadjuvant
chemotherapy for the clear cell ovarian cancer

- No concurrent maintenance corticosteroids except for short-term (< 5 days) use

- No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine,
phenobarbital), any other CYP3A4 inducer (e.g., rifampin, St. John wort), or strong
CYP3A4 inhibitors

- No other concurrent investigational agents

- No concurrent sunitinib