Polyglutamate Paclitaxel and Carboplatin in Treating Patients With Ovarian Epithelial, Peritoneal, or Fallopian Tube Cancer

Study 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.

Official Title
-----------------
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

Conditions
-----------------
Fallopian Tube Carcinoma, Malignant Ovarian Mixed Epithelial Tumor, Ovarian Brenner Tumor, Ovarian Clear Cell Cystadenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Mucinous Cystadenocarcinoma, Ovarian Serous Cystadenocarcinoma, Primary Peritoneal Carcinoma, Stage III Ovarian Cancer, Stage IV Ovarian Cancer, Undifferentiated Ovarian Carcinoma

Intervention / Treatment
-----------------
* Drug: Carboplatin
* Drug: Paclitaxel Poliglumex
* Other: Pharmacological Study


Participation Criteria
=================
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 Undifferentiated carcinoma Mixed epithelial carcinoma Malignant Brenner tumor 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (paclitaxel poliglumex, carboplatin)<br>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. | Drug: Carboplatin<br>* Given IV<br>* Other names: Ribocarbo;Drug: Paclitaxel Poliglumex<br>* Given IV<br>* Other names: Xyotax;Other: Pharmacological Study<br>* Correlative studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility, in terms of incidence of DLT, as assessed by CTC version 2.0 |  | 84 days (first 4 courses) | 
| Maximum tolerated dose (MTD) as assessed by CTC version 2.0 |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| Progression-free survival |  | Up to 5 years | 
| Response |  | Up to 5 years |