Topotecan, High-Dose Cyclophosphamide, Carboplatin, and an Autologous Peripheral Blood Cell Transplant in Treating Patients With Recurrent Ovarian Cancer or Primary Peritoneal Cancer

OBJECTIVES:

• To determine the maximum tolerated dose of topotecan hydrochloride combined with high-dose cyclophosphamide and carboplatin in the setting of autologous peripheral blood stem cell transplantation for relapsed, recurrent, or persistent ovarian epithelial or primary peritoneal cavity cancer.
• To assess the toxicity of this regimen.

OUTLINE: This is a dose escalation study of topotecan.

• Autologous hematopoietic stem cell collection: Patients receive filgrastim subcutaneously (SC) daily for 5 days. Patients undergo leukapheresis per standard practice until a minimum of 2 x10^6 CD34+ cells/kg are collected and cryopreserved.
• High-dose chemotherapy: Patients receive topotecan hydrochloride IV, cyclophosphamide IV, and carboplatin IV over 8 hours on days -6 to -3.
• Autologous peripheral stem cell reinfusion: Patients undergo autologous peripheral blood stem cell transplantation on day 0. Patients also receive sargramostim SC daily beginning on day 5 and continuing until blood counts recover.

After completion of study therapy, patients are followed monthly for 3 months, every 3 months for 2 years, and then every 6 months for 5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed ovarian epithelial or primary peritoneal cavity cancer

• Recurrent, relapsed, or persistent disease meeting 1 or more of the following criteria:

• Patients with a positive second-look laparotomy who are not candidates for higher priority GOG protocols
• Largest mass of recurrent disease ≤ 0.2 cm achieved by surgery or chemotherapy
• Achievement of complete response to 1 prior regimen of platinum-based chemotherapy with relapse > 6 months from last chemotherapy
• Achievement of partial response to 1 platinum-based chemotherapy regimen prior to study
• Histological proof of disease recurrence with or without a rising serum CA-125 level (relapsed or recurrent disease)
• The following histological cell types are allowed:

• Clear-cell adenocarcinoma
• Endometrioid adenocarcinoma
• Mixed epithelial carcinoma
• Mucinous adenocarcinoma
• Serous adenocarcinoma
• Undifferentiated carcinoma
• Must have unilateral bone marrow aspirate and biopsy with cytogenetics without evidence of metastatic ovarian carcinoma by conventional morphology within 1 month of registration
• Not eligible for GOG-164

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Creatinine ≤ 1.5 mg/dL
• Total bilirubin ≤ 2.0 mg/dL (≤ 5.0 mg/dL with metastatic disease)
• AST ≤ 2 times upper limit of normal (ULN) (≤ 600 units/mL with metastatic disease)
• Alkaline phosphatase ≤ 2 times ULN (unless related to metastatic disease)
• ANC ≥ 1,000/mm^3
• Platelets ≥ 100,000/mm^3
• Cardiac ejection fraction ≥ 45% by rest ECHO or MUGA
• FEV_1 ≥ 50% of predicted
• HIV negative
• No uncontrolled infection
• No severe medical or psychiatric illness, including any of the following:

• Renal failure
• Brittle insulin dependent diabetes mellitus
• Congestive heart failure
• History of myocardial infarction within the past 3 months
• Significant arrhythmia requiring medication
• Poorly controlled hypertension (diastolic blood pressure >100 mm Hg)
• History of hospitalization for severe depression or psychosis
• Significant non-neoplastic pulmonary disease
• Current alcohol or drug abuse.
• Active infection
• Active peptic ulcer disease
• No prior malignancy within the past 5 years except adequately treated basal cell or squamous cell carcinoma of the skin or in situ cervical carcinoma

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No more than 1 prior treatment regimen for this cancer
• More than 3 weeks since surgery
• No prior topotecan hydrochloride