A Multi-Institutional Phase II Study of Cyclophosphamide, Paclitaxel, Cisplatin With G-CSF for Patients With Newly Diagnosed Advanced Stage Ovarian Cancer

A supra-additive cytotoxic effect was seen when CAI and paclitaxel were given to human
ovarian cancer cells sequentially in tissue culture. We have demonstrated that CAI given for
8 days followed by paclitaxel is reasonably well tolerated and that paclitaxel administration
causes a dose-dependent increase in CAI plasma concentration. CAI is a cytostatic drug and
continuous exposure is needed. This study will evaluate the combination of continuously
administered CAI with three-weekly paclitaxel.

- INCLUSION CRITERIA:

All patients must have biopsy proven, newly diagnosed epithelial ovarian cancer, primary
epithelial fallopian tube cancer, or peritoneal surface carcinoma. Histopathologic
diagnosis must be confirmed in the pathology department of the treating institution prior
to initiation of therapy. Diagnosis will be confirmed in the Laboratory of Pathology,
National Cancer Institute. This confirmation is not necessary prior to entering the patient
onto protocol.

Patients must have FIGO stage III or IV disease and will undergo attempted surgical
debulking prior to the initiation of chemotherapy.

Patients must be able to begin therapy within 6 weeks of staging laparotomy and should have
an indwelling venous access device placed. A double lumen catheter is preferred.

Performance status of less than or equal to ECOG 2.

Patients must be able to give written informed consent and express a willingness to meet
all of the expected requirements of the protocol.

All patients must be registered by calling the Orkand Corporation at 301-402-1732 between
the hours of 8:30 AM and 5:00 PM EST; Eligibility criteria will be queried.

EXCLUSION CRITERIA:

Evidence CNS involvement (patients with normal clinical exam will not require a head CT
scan or MRI).

History of myocardial infarction or unstable dysrhythmia within 1 month of study entry.

Creatinine clearance of less than 60 cc/min, ANC less than 1000/cm3, platelet count less
than 1000,000/cm3.

History of active GI bleeding within the last 30 days.

Prior therapy other than surgery for this malignancy.

Abnormal PT, PTT, and bilirubin. SGOT greater than or equal to 3 times the upper limit of
normal.

Previous history of invasive malignancy.

Patients with ureteral obstruction must have this corrected prior to starting therapy.

Patients with germ cell, mixed Muellerian and borderline histologies are specifically
excluded.