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

Brief Title

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

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

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 Phase

Phase 1

Study Type

Interventional

Primary Outcome

Feasibility, in terms of incidence of DLT, as assessed by CTC version 2.0

Secondary Outcome

 Incidence of cumulative toxicity

Condition

Fallopian Tube Carcinoma

Intervention

Carboplatin

Study Arms / Comparison Groups

 Treatment (paclitaxel poliglumex, carboplatin)

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status

Drug

Estimated Enrollment

Start Date

April 2003

Primary Completion Date

January 2009

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

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Mark Morgan, ,

Location Countries

United States

Location Countries

United States

Administrative Informations

NCT ID

NCT00060359

Organization ID

GOG-9914

Secondary IDs

NCI-2012-02532

Responsible Party

Sponsor

Study Sponsor

Gynecologic Oncology Group

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Mark Morgan, Principal Investigator, Gynecologic Oncology Group

Verification Date

May 2015