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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


Phase 1/Phase 2
18 Years
65 Years
Not Enrolling
Female
Ovarian Cancer

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression free survival

Outcome Description:

Progression free survival is defined as the time from date of enrollment to the time of recurrence

Outcome Time Frame:

5 years

Safety Issue:

No

Principal Investigator

Karen K. Fields, MD

Investigator Role:

Study Chair

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute

Authority:

United States: Federal Government

Study ID:

MCC-12085

NCT ID:

NCT00005612

Start Date:

August 1999

Completion Date:

February 2004

Related Keywords:

  • Ovarian Cancer
  • stage III ovarian epithelial cancer
  • stage IV ovarian epithelial cancer
  • recurrent ovarian epithelial cancer
  • Ovarian Neoplasms
  • Neoplasm, Residual
  • Neoplasms, Glandular and Epithelial

Name

Location

H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612