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

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT00652691

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

213.1

Actual Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Giving colony-stimulating factors, such as G-CSF help stem cells move from the patient's bone marrow to the blood so they can be collected and stored. Combination chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

PURPOSE: This randomized trial is studying the side effects and best dose of topotecan when given together with high-dose cyclophosphamide, and carboplatin followed by an autologous peripheral blood stem cell transplant in treating patients with recurrent ovarian cancer or primary peritoneal cancer.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Peritoneal Cavity Cancer	Biological: filgrastim Drug: carboplatin Drug: cyclophosphamide Drug: topotecan hydrochloride Procedure: autologous hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Primary Purpose:

Treatment

Official Title:

A Dose Seeking Trial of Topotecan Combined With High-Dose Cyclophosphamide and Carboplatin With Peripheral Blood Stem Cell Transplant for the Treatment of Relapsed Ovarian Cancer and Primary Peritoneal Cancer

Actual Study Start Date :

Aug 1, 1998

Actual Primary Completion Date :

Jun 5, 2002

Actual Study Completion Date :

May 4, 2016

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of topotecan hydrochloride []
Toxicity according to NCI criteria []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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