A Dose-Escalating Phase I Study With an Expanded Cohort to Assess the Feasibility of CT-2103 and Carboplatin (NSC #214240) in Patients With Previously Untreated Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Carcinoma
A Dose-Escalating Phase I Study With an Expanded Cohort to Assess the Feasibility of CT-2103 and Carboplatin (NSC #214240) in Patients With Previously Untreated Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Carcinoma
This phase I trial is studying the side effects and best dose of polyglutamate paclitaxel when given together with carboplatin in treating patients with ovarian epithelial, peritoneal, or fallopian tube cancer. Drugs used in chemotherapy such as polyglutamate paclitaxel and carboplatin use different ways to stop tumor cells from dividing so they stop growing or die. Polyglutamate paclitaxel may be able to deliver the drug directly to tumor cells while leaving normal cells undamaged. Combining polyglutamate paclitaxel with carboplatin may kill more tumor cells.
PRIMARY OBJECTIVES:
I. 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.
II. Determine the feasibility of this regimen at the MTD in an expanded cohort of patients.
III. Determine the response rate and progression-free survival of patients treated with this regimen in the expanded cohort.
IV. Determine the toxicity profile of this regimen in these patients. V. 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.
Inclusion Criteria:
Histologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube carcinoma
The following histologic epithelial cell types are eligible:
No epithelial tumors of low malignant potential (borderline tumors)
Surgery performed within the past 12 weeks
Performance status - GOG 0-2
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
No active bleeding
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
Creatinine no greater than 1.5 times ULN
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
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
More than 3 years since prior adjuvant chemotherapy for localized breast cancer (must be free of recurrent or metastatic disease)
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
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