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Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Ovarian Epithelial Cancer
This study is ongoing, but not recruiting participants.
First Received: May 2, 2000   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: H. Lee Moffitt Cancer Center and Research Institute
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005612
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Biological: filgrastim
Drug: carboplatin
Drug: cyclophosphamide
Drug: etoposide
Drug: paclitaxel
Drug: topotecan hydrochloride
Procedure: peripheral blood stem cell transplantation
Phase I
Phase II

MedlinePlus related topics: Cancer Ovarian Cancer
Drug Information available for: Cyclophosphamide Paclitaxel Etoposide Carboplatin Etoposide phosphate Topotecan hydrochloride Filgrastim Topotecan
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: 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

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: March 2000
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005612

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Investigators
Study Chair: Karen K. Fields, MD H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000067742, MCC-12085, MCC-IRB-5418, NCI-G00-1745
Study First Received: May 2, 2000
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00005612     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer

Study placed in the following topic categories:
Neoplasm, Residual
Immunologic Factors
Gonadal Disorders
Urogenital Neoplasms
Ovarian Diseases
Cyclophosphamide
Etoposide phosphate
Genital Diseases, Female
Ovarian Cancer
Etoposide
Alkylating Agents
Endocrine Gland Neoplasms
Ovarian Neoplasms
Genital Neoplasms, Female
Endocrine System Diseases
Antimitotic Agents
Carboplatin
Ovarian Epithelial Cancer
Immunosuppressive Agents
Recurrence
Paclitaxel
Tubulin Modulators
Endocrinopathy
Antineoplastic Agents, Alkylating
Topotecan
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

Additional relevant MeSH terms:
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gonadal Disorders
Physiological Effects of Drugs
Urogenital Neoplasms
Cyclophosphamide
Ovarian Diseases
Genital Diseases, Female
Neoplasms by Site
Therapeutic Uses
Etoposide
Alkylating Agents
Endocrine Gland Neoplasms
Ovarian Neoplasms
Mitosis Modulators
Genital Neoplasms, Female
Endocrine System Diseases
Enzyme Inhibitors
Antimitotic Agents
Carboplatin
Immunosuppressive Agents
Pharmacologic Actions
Adnexal Diseases
Neoplasms
Paclitaxel
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Topotecan

ClinicalTrials.gov processed this record on May 07, 2009