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
Overview
- Phase
- Phase 1
- Intervention
- Carboplatin
- Conditions
- Fallopian Tube Carcinoma
- Sponsor
- Gynecologic Oncology Group
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose (MTD) as assessed by CTC version 2.0
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (paclitaxel poliglumex, carboplatin)
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 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.
Intervention: Carboplatin
Treatment (paclitaxel poliglumex, carboplatin)
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 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.
Intervention: Paclitaxel Poliglumex
Treatment (paclitaxel poliglumex, carboplatin)
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 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.
Intervention: Pharmacological Study
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD) as assessed by CTC version 2.0
Time Frame: 21 days
Feasibility, in terms of incidence of DLT, as assessed by CTC version 2.0
Time Frame: 84 days (first 4 courses)
Secondary Outcomes
- Progression-free survival(Up to 5 years)
- Incidence of cumulative toxicity(168 days (8 courses))
- Pharmacokinetics and pharmacodynamics of conjugated taxanes, unconjugated paclitaxel and carboplatin, as assessed by serum and urine measurements(84 days (courses 1-4))
- Response(Up to 5 years)