Paclitaxel, Carboplatin, and Topotecan in Patients With Ovarian Cancer

Phase III Multicenter Study in Epithelial Ovarian Carcinoma FIGO Stage IIB-IV Comparing Treatment With Paclitaxel and Carboplatin to Paclitaxel and Carboplatin Sequentially Followed by Topotecan

The purpose of this study is to determine whether the triple combination of Carboplatin, Paclitaxel and Topotecan has a superior clinical outcome in the treatment of ovarian cancer compared with the combination of Carboplatin and Paclitaxel.

Carboplatin-Paclitaxel is the current standard in the first-line treatment of advanced ovarian cancer. One option to further improve the therapeutic results is the incorporation of a third, non-cross-resistant drug into first line chemotherapy of advanced ovarian cancer. In two separate, single center phase II studies, a different combination of the three active agents (Carboplatin, Paclitaxel and Topotecan) has been tested. In these studies, Carboplatin and Paclitaxel were given at standard doses and schedules, followed sequentially by Topotecan which was well tolerated at a dose of 1.25 mg/m2/day given for five days and repeated every 21 days. The prolonged therapy is not associated with cumulative toxicity and the compliance of the patients was good.

Study Hypothesis/Comparison: The triple combination (Carboplatin/Paclitaxel/Topotecan) yields superior outcome in the treatment of first-line ovarian cancer compared with the combination of Carboplatin + Paclitaxel

Inclusion Criteria:

• Histologically proven epithelial carcinoma of the ovary or of the fallopian tube or extraovarian papillary serous carcinoma with extent to the ovary

• International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IV, regardless of measurable or non-measurable disease

• No prior chemo- or radiotherapy

• Adequate hematologic, renal and hepatic function:

  • ANC ≥ 1.5 x 10^9/L,
  • Platelet counts ≥ 100 x 10^9/L,
  • Total bilirubin ≤ 1.5 x upper normal limit,
  • Alkaline Phosphatase ≤ 3 x upper normal limit,
  • Serum creatinine ≤ 1.25 upper normal limit,
  • Estimated GFR ≥ 60 ml/min

• Performance status 0-2 (ECOG)

• Life expectancy must be greater than 12 weeks

Exclusion Criteria:

• Non-epithelial tumors or mixed epithelial/non-epithelial tumors (e.g. mixed Mullerian tumors) or tumors of low malignant potential (borderline tumors)
• Prior treatment with chemo- or radiotherapy
• Administration of other simultaneous chemotherapeutic drugs or hormonal therapy or simultaneous radiotherapy during the study treatment period or planned whole abdominal radiotherapy
• History of congestive heart failure
• Symptomatic brain metastasis
• Complete bowel obstruction
• Dementia
• Active infection or other serious underlying medical condition
• Pre-existing motor or sensory neurologic pathology