Paclitaxel, Cisplatin, and Topotecan With or Without Filgrastim in Treating Patients With Newly Diagnosed Stage III or Stage IV Epithelial Ovarian Cancer

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00002913

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

Phase I trial to study the effectiveness of paclitaxel, cisplatin, and topotecan with or without filgrastim in treating patients who have newly diagnosed stage III or stage IV epithelial ovarian cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy

Condition or Disease	Intervention/Treatment	Phase
Brenner Tumor Ovarian Clear Cell Cystadenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian Mixed Epithelial Carcinoma Ovarian Mucinous Cystadenocarcinoma Ovarian Serous Cystadenocarcinoma Ovarian Undifferentiated Adenocarcinoma Stage III Ovarian Epithelial Cancer Stage IV Ovarian Epithelial Cancer	Drug: paclitaxel Drug: cisplatin Drug: topotecan hydrochloride Biological: filgrastim	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

Determine the maximum tolerated doses of paclitaxel, cisplatin, and topotecan administered together with or without filgrastim (G-CSF) in patients with newly diagnosed advanced ovarian cancer.
Describe and quantitate the clinical toxic effects of combination chemotherapy with paclitaxel, cisplatin, and topotecan with or without G-CSF.
Assess preliminary evidence of antitumor activity of this combination chemotherapy in these patients.

OUTLINE: This is a dose escalation study of topotecan.

Cohorts of 4-6 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 2 of 6 patients experience dose limiting toxicities.

Patients are followed as clinically indicated.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

PHASE I STUDY OF PACLITAXEL COMBINED WITH TOPOTECAN AND CISPLATIN AND G-CSF IN PATIENTS WITH NEWLY DIAGNOSED ADVANCED OVARIAN EPITHELIAL MALIGNANCIES

Study Start Date :

Dec 1, 1996

Actual Primary Completion Date :

Jul 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (paclitaxel, cisplatin, topotecan hydrochloride) Patients receive paclitaxel IV over 3 hours and cisplatin IV on day 1, followed by topotecan IV over 30 minutes on days 1-3. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 4 and continuing until blood counts recover. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 4-6 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 2 of 6 patients experience dose limiting toxicities.	Drug: paclitaxel Given IV Other Names: Anzatax Asotax TAX Taxol Drug: cisplatin Given IV Other Names: CACP CDDP CPDD DDP Drug: topotecan hydrochloride Given IV Other Names: hycamptamine Hycamtin SKF S-104864-A TOPO Biological: filgrastim Given SC Other Names: G-CSF Neupogen

Arm

Intervention/Treatment

Experimental: Treatment (paclitaxel, cisplatin, topotecan hydrochloride)

Patients receive paclitaxel IV over 3 hours and cisplatin IV on day 1, followed by topotecan IV over 30 minutes on days 1-3. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 4 and continuing until blood counts recover. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 4-6 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 2 of 6 patients experience dose limiting toxicities.

Drug: paclitaxel

Given IV

Other Names:

Anzatax

Asotax

TAX

Taxol

Drug: cisplatin

Given IV

Other Names:

CACP

CDDP

CPDD

DDP

Drug: topotecan hydrochloride

Given IV

Other Names:

hycamptamine

Hycamtin

SKF S-104864-A

TOPO

Biological: filgrastim

Given SC

Other Names:

G-CSF

Neupogen

Outcome Measures

Primary Outcome Measures

Maximally tolerated doses (MTDs) of the combination of paclitaxel, Topotecan, and cisplatin administered without and with G-CSF based on dose-limiting toxicities (DLT) graded according to GOG Common Toxicity Criteria [3 weeks]

Secondary Outcome Measures

Overall survival [Up to 10 years]
Progression-free survival [Up to 10 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed epithelial ovarian carcinoma
No borderline ovarian carcinoma
Stage III/IV disease that has been suboptimally or optimally debulked
The following histologies are eligible:
Adenocarcinoma (unspecified)
Mucinous cystadenocarcinoma
Clear cell adenocarcinoma
Serous cystadenocarcinoma
Endometrioid adenocarcinoma
Transitional cell carcinoma
Malignant Brenner's tumor
Undifferentiated carcinoma
Mixed epithelial carcinoma
Extraovarian papillary serous cystadenocarcinoma
Measurable or evaluable disease
Performance status - GOG 0-1
Enabling completion of at least 2 courses of therapy
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Bilirubin no greater than 1.5 mg/dL
Creatinine clearance at least 60 mL/min
No myocardial infarction within 6 months
No congestive heart failure
No unstable or uncontrolled angina
No history of cardiac arrhythmia requiring anti-arrhythmia medication
No uncontrolled hypertension
No hypersensitivity to E. coli-derived drug preparation
No active infection
No sensory neuropathy
No other malignancies within the past 5 years except nonmelanomatous skin cancer
No prior chemotherapy
No prior radiotherapy
Recovered from any recent surgery