Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003732
• Other study ID #: DAN-104864/373
• Secondary ID: CDR0000066847DAN
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: August 9, 2013
• Start date: September 1998
• Est. completion date: September 2005

Study information

• Verified date: July 2002
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of topotecan combined with carboplatin and paclitaxel in treating patients who have stage II, stage III, or stage IV ovarian cancer.

Description:

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: September 2005
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• carboplatin

• paclitaxel

• topotecan hydrochloride

Locations

Country	Name	City	State
Denmark	Rigshospitalet - Copenhagen University Hospital	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose and dose-limiting toxicity of topotecan			Yes
Primary	Toxic effects			Yes
Primary	Antitumor activity			No