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

Study Overview
=================
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

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. 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. II. Describe and quantitate the clinical toxic effects of combination chemotherapy with paclitaxel, cisplatin, and topotecan with or without G-CSF. III. Assess preliminary evidence of antitumor activity of this combination chemotherapy in these patients. OUTLINE: This is a dose escalation study of topotecan. 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. Patients are followed as clinically indicated.

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

Conditions
-----------------
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

Intervention / Treatment
-----------------
* Drug: paclitaxel
* Drug: cisplatin
* Drug: topotecan hydrochloride
* Biological: filgrastim


Participation Criteria
=================
Eligibility Criteria
-----------------
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
Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (paclitaxel, cisplatin, topotecan hydrochloride)<br>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<br>* Given IV<br>* Other names: Taxol;Drug: cisplatin<br>* Given IV<br>* Other names: DDP;Drug: topotecan hydrochloride<br>* Given IV<br>* Other names: TOPO;Biological: filgrastim<br>* Given SC<br>* Other names: Neupogen;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Up to 10 years | 
| Progression-free survival |  | Up to 10 years |