A Phase I/II Study to Determine the Maximum Tolerated Doses of Oral Topotecan, Carboplatin and Paclitaxel Administered Every 21 Days to Patients With Epithelial Ovarian Cancer Stages IIb, IIc, III and IV
18 Years
N/A
Female
Ovarian Cancer
Trial Information
A Phase I/II Study to Determine the Maximum Tolerated Doses of Oral Topotecan, Carboplatin and Paclitaxel Administered Every 21 Days to Patients With Epithelial Ovarian Cancer Stages IIb, IIc, III and IV
OBJECTIVES:
- Determine the maximum tolerated dose, dose-limiting toxicity, and quantitative and
qualitative toxic effects of oral topotecan combined with intravenous carboplatin and
paclitaxel in patients with stage IIB, IIC, III, or IV ovarian epithelial cancer.
(phase I closed to accrual 12/21/00)
- Evaluate the anti-tumor activity of this regimen in this patient population.
OUTLINE: This is a multicenter, dose-escalation study of topotecan.
Patients receive oral topotecan on days 1-5 and paclitaxel IV over 3 hours followed by
carboplatin IV over 30 minutes on day 5. Courses repeat every 21 days for a maximum of 6
courses in the absence of disease progression or unacceptable toxicity.
- Phase I: Cohorts of 3-6 patients receive escalating doses of topotecan until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2
of 6 patients experience dose-limiting toxicity. (phase I closed to accrual 12/21/00)
- Phase II: An additional 50 patients receive up to 6 courses of treatment as in phase I
at the MTD.
Patients are followed every 3 months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 80 patients (30 in phase I and 50 in phase II) will be accrued
for this study. (phase I closed to accrual 12/21/00)
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed stage IIB, IIC, III, or IV ovarian epithelial cancer
- Measurable or evaluable lesion or microscopic residual disease after first surgery
(phase II patients)
- No brain and/or leptomeningeal metastases by CT scan or MRI unless asymptomatic
without corticosteroid therapy
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- ECOG 0-2
Life expectancy:
- At least 3 months
Hematopoietic:
- Hemoglobin at least 9.0 g/dL
- WBC at least 3,500/mm3
- Absolute neutrophil count at least 1,500/mm3
- Platelet count at least 100,000/mm3
Hepatic:
- Bilirubin no greater than 1.5 times upper limit of normal (ULN) unless liver
metastases present
- Alkaline phosphatase no greater than 2 times ULN*
- SGOT no greater than 2 times ULN* NOTE: *No greater than 5 times ULN if liver
metastases present
Renal:
- Creatinine no greater than 1.5 times ULN
- Creatinine clearance at least 60 mL/min
Cardiovascular:
- No symptomatic cardiac disease, including clinical congestive heart failure or
arrhythmias requiring treatment
- No myocardial infarction within the past 3 months
Other:
- No other malignancy except basal or squamous cell skin cancer or carcinoma in situ of
the cervix
- No uncontrolled infection
- No complete bowel obstruction or other condition that would affect GI absorption or
motility
- No concurrent medical condition for which treatment with platinum, taxane, or
camptothecin analogues are contraindicated
- No other concurrent medical conditions that would preclude study
- No mental disease
- No history of allergy to platinum or taxanes, including drugs containing cremophor
(e.g., cyclosporine or vitamin K)
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No concurrent immunotherapy
Chemotherapy:
- No prior camptothecin analogue
- No prior chemotherapy for ovarian cancer
- No other concurrent chemotherapy
Endocrine therapy:
- See Disease Characteristics
- No concurrent hormonal therapy other than estrogen replacement
Radiotherapy:
- No concurrent radiotherapy
Surgery:
- See Disease Characteristics
Other:
- At least 30 days or 5 half-lives since any prior investigational therapy
- No other concurrent investigational therapy
- No concurrent metoclopramide or cisapride
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose and dose-limiting toxicity of topotecan
Safety Issue:
Yes
Principal Investigator
Svend Aage Engelholm, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Rigshospitalet, Denmark
Authority:
Unspecified
Study ID:
CDR0000066847
NCT ID:
NCT00003732
Start Date:
September 1998
Completion Date:
Related Keywords:
- Ovarian Cancer
- stage IIB ovarian epithelial cancer
- stage IIC ovarian epithelial cancer
- stage IIIA ovarian epithelial cancer
- stage IIIB ovarian epithelial cancer
- stage IIIC ovarian epithelial cancer
- stage IV ovarian epithelial cancer
- Ovarian Neoplasms
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