Trial Information

A Phase II Study of Carboplatin and Paclitaxel as Neoadjuvant Chemotherapy Followed by Interval Cytoreduction in Women With Advanced Staged Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma for High-Risk Surgical Candidates or Patients Unlikely to be Optimally Surgically Cytoreduced

OBJECTIVES:

Primary

- Determine whether at least 50% of patients with advanced ovarian epithelial, fallopian
tube, or primary peritoneal cavity cancer are able to achieve optimal cytoreduction (to
< 1 centimeter of remaining disease) after neoadjuvant chemotherapy comprising
paclitaxel and carboplatin.

Secondary

- Determine the frequency and severity of toxicity associated with this regimen in
patients who are high-risk surgical candidates or in patients unlikely to achieve
optimal surgical cytoreduction.

- Determine if extreme drug resistance assay profiles change after neoadjuvant
chemotherapy.

- Determine how thrombospondin-1 (TSP-1), tumor protein 53 (p53), and tumor vessel
density change after administration of neoadjuvant chemotherapy.

- Assess the quality of life of patients receiving neoadjuvant chemotherapy.

- Obtain estimates of tumor response after administration of neoadjuvant chemotherapy.

- Determine whether serum cancer antigen 125 (CA-125) at the time of cytoreduction is
associated with the ability to optimally reduce the patients.

OUTLINE: This is an open-label study.

Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30
minutes on day 1. Treatment repeats every 3 weeks for up to 4 courses in the absence of
disease progression or unacceptable toxicity. Within 4-6 weeks after the fourth course of
chemotherapy, patients undergo interval cytoreductive surgery.

Patients who are unable to undergo surgery receive 2 additional courses of chemotherapy and
are re-evaluated for surgery after the sixth course of chemotherapy.

Within 4 weeks after surgery, patients receive 2 additional courses of chemotherapy.

Quality of life is assessed periodically.

Tumor samples are obtained via laparoscopic or percutaneous biopsy prior to beginning
chemotherapy and during interval cytoreduction. Tissue is examined by immunohistochemistry
staining for p53, TSP-1, microvessel density (CD31), angiogenesis, membrane protein BCL-2,
and multidrug resistant gene 1 (MDR-1). Gene array analysis and extreme drug resistant
assays are also performed.

After completion of study treatment, patients are followed every 3 months for 2 years.