Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Ovarian Epithelial Cancer (ETC)

September 24, 2012 updated by: H. Lee Moffitt Cancer Center and Research Institute

A Phase I/II Study of Intensive-Dose Etoposide, Topotecan and Carboplatin (ETC) Followed by Autologous Stem Cell Rescue in Chemosensitive Ovarian Cancer Patients With Either Minimal Residual Disease or at First Relapse

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with autologous peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy followed by peripheral stem cell transplantation in treating patients who have ovarian epithelial cancer.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES: I. Determine the toxicity and potential efficacy of high dose chemotherapy (HDC) comprised of etoposide, topotecan, and carboplatin (ETC) followed by autologous stem cell transplantation in patients with ovarian epithelial cancer. II. Determine the maximum tolerated dose of topotecan when combined with etoposide and carboplatin in these patients. III. Determine the disease free survival (DFS) and overall survival (OS) in patients treated with this regimen. IV. Measure the amount and subcellular location of DNA topoisomerase I and II- alpha in ovarian cancer biopsies before HDC and at relapse to determine the role of alterations of topoisomerases in the drug resistance of ovarian cancer. V. Correlate the amount and location of both enzymes before HDC with clinical outcome (DFS and OS) and plasma concentrations of topotecan and carboplatin in these patients. VI. Correlate the levels of signal transducers and activators of transcription (STAT) and expression of bcl-2 family proteins with response to chemotherapy and clinical outcome (DFS and OS) in these patients. VII. Measure the levels of STAT and determine the expression of bcl-2 family proteins in tumor biopsies before HDC and at relapse to determine the role of these cellular pathways in drug response. VIII. Determine the pharmacokinetic and pharmacodynamic relationship of high dose topotecan combined with carboplatin in these patients.

OUTLINE: This is a dose escalation study of topotecan. Mobilization: After completion of salvage chemotherapy and within 6 weeks of second look laparotomy, patients receive cyclophosphamide IV over 2 hours and paclitaxel IV over 2 hours for 2 days. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning 24 hours after completion of chemotherapy and continuing until autologous peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells. High dose chemotherapy: After priming chemotherapy and within 6 weeks of second look laparotomy, patients receive carboplatin IV over 1 hour on days -8 to -6; topotecan IV over 30 minutes on days -7 to -5 (beginning 12 hours after completion of carboplatin infusion); and etoposide IV over 4 hours on days -5 to -3 (beginning 12 hours after completion of the last topotecan infusion). Cohorts of 4-12 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 6 or more of 12 patients experience dose limiting toxicity. Transplantation: PBSC are reinfused on day 0. Patients are followed at 3 and 6 months, then annually thereafter.

PROJECTED ACCRUAL: Approximately 4-30 patients will be accrued for this study within 3-4 years.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS: Histologically proven stage IIIC ovarian epithelial cancer Chemosensitive to 6-8 courses of standard dose adjuvant chemotherapy (one regimen), such as cisplatin or carboplatin in combination with paclitaxel, or any other standard dose regimen Residual disease (no greater than 1 cm) following second look laparotomy Ineligible if no microscopic disease present following induction chemotherapy OR Histologically proven newly diagnosed stage IV ovarian epithelial cancer Achieved at least partial response (PR) (80% or greater reduction in tumor by CT scan) following six courses of standard dose chemotherapy (one regimen) OR Residual disease (no greater than 1 cm) or no disease determined at the time of second look laparotomy OR Histologically proven relapsed ovarian epithelial cancer Relapse following standard dose chemotherapy Chemosensitive Achieved at least PR after 4-6 courses of salvage chemotherapy (total of 2 regimens) No more than a six week interval between completion of standard dose chemotherapy and second look laparotomy

PATIENT CHARACTERISTICS: Age: 18 to 65 Performance status: ECOG 0 or 1 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL ALT or AST no greater than 2.5 times normal Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: Ejection fraction at least 50% by MUGA scan No severe cardiac dysfunction or major heart disease No angina pectoris No ventricular dysrhythmias Essential hypertension allowed if controlled with medication(s) Pulmonary: DLCO at least 50% predicted No symptomatic obstructive or restrictive pulmonary disease Other: No active infections HIV negative No uncontrolled insulin dependent diabetes mellitus No uncompensated major thyroid or adrenal dysfunction No other malignancy within the past 5 years except nonmelanomatous skin cancer Not pregnant or nursing Negative pregnancy test

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No prior topotecan Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: See Disease Characteristics Other: No concurrent nitroglycerin preparations or antiarrhythmic drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 5 years
Progression free survival is defined as the time from date of enrollment to the time of recurrence
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Karen K. Fields, MD, H. Lee Moffitt Cancer Center and Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 1999

Primary Completion (Actual)

February 1, 2004

Study Completion (Actual)

February 1, 2004

Study Registration Dates

First Submitted

May 2, 2000

First Submitted That Met QC Criteria

April 30, 2004

First Posted (Estimate)

May 3, 2004

Study Record Updates

Last Update Posted (Estimate)

September 26, 2012

Last Update Submitted That Met QC Criteria

September 24, 2012

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-12085
  • MCC-IRB-5418 (Other Identifier: University of South Florida IRB)
  • NCI-G00-1745 (Other Grant/Funding Number: NCI)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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