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

Phase 1

Completed

• Conditions: Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Brenner Tumor; Fallopian Tube Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Mucinous Cystadenocarcinoma; Stage III Ovarian Cancer; Stage IV Ovarian Cancer
• Interventions: Drug: Carboplatin; Drug: Paclitaxel Poliglumex; Other: Pharmacological Study

• Registration Number: NCT00060359
• Lead Sponsor: Gynecologic Oncology Group

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.

Study Timeline

• Study Start: 2003-04
• Study First Submitted: 2003-05-06
• Study First Submitted QC: 2003-05-06
• Study First Posted: 2003-05-07
• Primary Completion: 2009-01
• Status Verified: 2015-05
• Last Update Submitted: 2015-05-07
• Last Update Posted: 2015-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 32

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (paclitaxel poliglumex, carboplatin)	Pharmacological 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 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.
Treatment (paclitaxel poliglumex, carboplatin)	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.
Treatment (paclitaxel poliglumex, carboplatin)	Paclitaxel Poliglumex	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.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) as assessed by CTC version 2.0	21 days
Feasibility, in terms of incidence of DLT, as assessed by CTC version 2.0	84 days (first 4 courses)

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Gynecologic Oncology Group; 🇺🇸 Philadelphia, Pennsylvania, United States