• Maximum tolerated dose (MTD) as assessed by CTC version 2.0 during the first course of therapy [ Designated as safety issue: Yes ]
  
• Feasibility as assessed by CTC version 2.0 weekly during treatment for up to 8 courses [ Designated as safety issue: No ]
  

• Response rates as measured by RECIST criteria after courses 4 and 8 [ Designated as safety issue: No ]
  
• Pharmacokinetics as assessed by serum and urine measurements during courses 1-4 [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine the maximum tolerated dose (MTD) of polyglutamate paclitaxel in combination with carboplatin in patients with chemotherapy-naïve ovarian epithelial, primary peritoneal, or fallopian tube carcinoma.
• Determine the feasibility of this regimen at the MTD in an expanded cohort of patients.
• Determine the response rate and progression-free survival of patients treated with this regimen in the expanded cohort.
• Determine the toxicity profile of this regimen in these patients.
• Determine the pharmacokinetics and pharmacodynamics of this drug combination in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study of polyglutamate paclitaxel (CT-2103) followed by a feasibility, multicenter study.

• Dose-escalation phase: Patients receive CT-2103 IV over 10 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of CT-2103 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of treatment.

• Feasibility phase: Once the MTD of CT-2103 is determined, an additional 20-40 patients receive treatment at that dose level combined with carboplatin as above.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 3-64 patients (3-24 for dose-escalation phase and 20-40 for feasibility phase) will be accrued for this study within 4-10 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube carcinoma

  • Stage III or IV
  • Optimal (no greater than 1 cm) or suboptimal residual disease after initial surgery

• The following histologic epithelial cell types are eligible:

  • Serous adenocarcinoma
  • Mucinous adenocarcinoma
  • Clear cell adenocarcinoma
  • Transitional cell carcinoma
  • Adenocarcinoma not otherwise specified
  • Endometrioid adenocarcinoma
  • Undifferentiated carcinoma
  • Mixed epithelial carcinoma
  • Malignant Brenner tumor
• No epithelial tumors of low malignant potential (borderline tumors)
• Surgery performed within the past 12 weeks

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• GOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No active bleeding

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 2.5 times ULN (5 times ULN if liver metastasis)
• Alkaline phosphatase no greater than 2.5 times ULN (5 times ULN if liver metastasis)
• No acute hepatitis
• PT and PTT normal

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• Cardiac conduction abnormalities (e.g., bundle branch block or heart block) allowed provided cardiac status has been stable for the past 6 months
• No myocardial infarction within the past 6 months
• No unstable angina

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No neuropathy (sensory or motor) grade 2 or worse
• No other invasive malignancies within the past 5 years except nonmelanoma skin cancer or localized breast cancer
• No active infection requiring antibiotics
• No circumstances that would preclude study completion or follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 3 years since prior adjuvant chemotherapy for localized breast cancer (must be free of recurrent or metastatic disease)

Endocrine therapy

• Not specified

Radiotherapy

• More than 3 years since prior radiotherapy for localized cancer of the breast, head and neck, or skin (must be free of recurrent or metastatic disease)
• No prior radiotherapy to any portion of the abdominal cavity or pelvis

Surgery

• See Disease Characteristics

Other

• No prior treatment, other than debulking surgery, for this cancer
• No prior treatment for another cancer that would contraindicate this protocol therapy
• No concurrent amifostine or other protective reagents