Phase II Study of Modified Triple Doublet Therapy in Women With Newly Diagnosed Mullerian Carcinoma

Objective: To evaluate a novel regimen in ovarian carcinoma with an aim of demonstrating a higher than 50% laparotomy defined response rate. This rate is defined as the proportion of patients achieving either a pathologic complete response or a microscopic positive second look at the conclusion of therapy.

Primary study goals:

· To determine the efficacy of a triple doublet regimen in carefully defined cohorts of patients as defined by the surgical defined response rate

Secondary study goals:

• To evaluate incidence of tubulin mutations in primary and secondary surgical specimens.
• To evaluate changes in IL-6, IL-8, VEGF, and FGF, at primary diagnosis, during and at the conclusion of therapy.
• To describe initial IL-6, IL-8, and FGF levels in patients who ultimately achieve pathologic remission vs those with gross residual disease.

Patients will recieve 3 cycles of carboplatin and gemcitabine followed by 3 cycles of taxol and carboplatin and then three cycles of adriamycin and topotecan. All patients with a clinically complete response will then undergo second look operation to determine pathologically defined response.

• SLO = Second Look Operation

Inclusion criteria

• Histologically confirmed epithelial carcinoma of müllerian origin. Specifically, ovarian, primary peritoneal and tubal carcinoma will be allowed. All histologic subtypes are eligible.

• Patients must have undergone an attempt at aggressive surgical debulking or alternatively be eligible for interim debulking after cycle #3. Patients debulked to no evidence of disease, microscopic disease or gross residual disease are eligible.
• Stage II, III or IV disease. Patients with disease outside the abdominal cavity are eligible unless presentation includes brain metastases.
• Able and willing to undergo a second look staging laparotomy.
• Patients must give written informed consent.
• Patient must be ag· Performance status (ECOG) >2.
• Previous chemotherapy.
• Creatinine > 1.5
• History of recent MI or congestive heart failure within 6 months of surgery
• SGOT > 2x ULN, bilirubin > 1.5 X ULN
• Concurrent invasive malignancy. (Patients with concurrent superficial endometrial carcinoma are eligible if their endometrial carcinoma is superficial or invades less than 50% the thickness of the myometrium).
• Known hypersensitivity to E.coli derived products?
• Active psychiatric or mental illness that makes informed consent or careful clinical follow-up unlikely e 18 years or older.
• Adequate bone marrow function with an ANC > 2,500 and Platelets >100,000/mm3.

Exclusion criteria