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

Sponsor

Gynecologic Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00060359

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Carboplatin Drug: Paclitaxel Poliglumex Other: Pharmacological Study	Phase 1

Detailed Description

PRIMARY 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. 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.

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Apr 1, 2003

Actual Primary Completion Date :

Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Carboplatin Given IV Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplat Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo Drug: Paclitaxel Poliglumex Given IV Other Names: CT-2103 Paclitaxel Polyglutamate Paclitaxel-Polyglutamate Polymer PG-TXL Poly-L-Glutamic acid-Paclitaxel Conjugate Polyglutamic Acid Paclitaxel Xyotax Other: Pharmacological Study Correlative studies

Arm

Intervention/Treatment

Experimental: 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.

Drug: Carboplatin

Given IV

Other Names:

Blastocarb

Carboplat

Carboplatin Hexal

Carboplatino

Carbosin

Carbosol

Carbotec

CBDCA

Displata

Ercar

JM-8

Nealorin

Novoplatinum

Paraplat

Paraplatin

Paraplatin AQ

Paraplatine

Platinwas

Ribocarbo

Drug: Paclitaxel Poliglumex

Given IV

Other Names:

CT-2103

Paclitaxel Polyglutamate

Paclitaxel-Polyglutamate Polymer

PG-TXL

Poly-L-Glutamic acid-Paclitaxel Conjugate

Polyglutamic Acid Paclitaxel

Xyotax

Other: Pharmacological Study

Correlative studies

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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