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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

Phase 2
18 Years
Open (Enrolling)
Ovarian Cancer

Thank you

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


- 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


- 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



- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- At least 3 months


- 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


- 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


- Creatinine no greater than 1.5 times ULN

- Creatinine clearance at least 60 mL/min


- No symptomatic cardiac disease, including clinical congestive heart failure or
arrhythmias requiring treatment

- No myocardial infarction within the past 3 months


- 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

- 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


Biologic therapy:

- No concurrent immunotherapy


- 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


- No concurrent radiotherapy


- See Disease Characteristics


- 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:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose and dose-limiting toxicity of topotecan

Safety Issue:


Principal Investigator

Svend Aage Engelholm, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Rigshospitalet, Denmark



Study ID:




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