Phase I/II Study of High Dose Topotecan, Mitoxantrone and Thiotepa (TMT) Followed by Autologous Stem Cell Transplant in Patients With Recurrent Platinum Resistant Ovarian Cancer
mitoxantrone hydrochloride
+ thiotepa
+ topotecan hydrochloride
Urogenital Diseases+16
+ Genital Diseases
+ Adnexal Diseases
Treatment Study
Summary
Study start date: December 1, 1997
Actual date on which the first participant was enrolled.OBJECTIVES: I. Determine the maximum tolerated dose and the dose limiting toxicities of topotecan, mitoxantrone, and thiotepa given in combination followed by autologous peripheral blood stem cell transplantation in patients with recurrent or refractory platinum resistant epithelial ovarian cancer. II. Determine the progression-free survival and overall survival of these patients after this therapy. OUTLINE: This is a dose escalation study of topotecan. All patients have peripheral stem cells collected. Patients then receive topotecan according to an escalating dose schedule, and mitoxantrone and thiotepa on a fixed dose schedule. Patients receive topotecan by continuous infusion for 24 hours on days 1-3, mitoxantrone intravenously over 1 hour on days 1-3, and thiotepa intravenously over 4 hours on days 1-3, followed 48 hours later by infusion of their peripheral stem cells. Patients may receive a second course of chemotherapy and peripheral stem cell transplantation in the absence of disease progression and unacceptable toxicity. Dose escalation of topotecan continues in cohorts of 3-6 patients each until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 or more patients experience dose limiting toxicity. Patients are followed every week for the first month, then every month for 6 months, every 3 months for 1 year, and then every 6 months. PROJECTED ACCRUAL: A total of 21-50 patients will be accrued for this study.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.50 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Female
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: Histologically confirmed stage III or IV epithelial ovarian cancer that is refractory to platinum therapy or has relapsed within 12 months after platinum therapy Minimal residual disease by laparotomy Must have adequate number of peripheral stem cells collected No intraabdominal, pelvic disease, or other disease greater than 1 cm No brain metastasis PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0-2 Life expectancy: At least 12 weeks Hematopoietic: WBC greater than 3,500/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin less than 2 times the upper limit of normal (ULN) Serum transaminases less than 2 times ULN Renal: Creatinine clearance greater than 60 mL/min Cardiovascular: Cardiac ejection fraction at least 45% No active angina No uncontrolled hypertension Pulmonary: FEV1, vital capacity, and diffusion capacity greater than 50% of predicted Other: Not HIV positive No active hepatitis B or C infection Not pregnant No concurrent malignancy except basal cell or squamous cell carcinoma of the skin No serious medical conditions such as uncontrolled diabetes mellitus PRIOR CONCURRENT THERAPY: Biologic therapy: No immunotherapy within the past 4 weeks No concurrent immunotherapy Chemotherapy: No chemotherapy within the past 4 weeks No mitomycin within the past 6 weeks No other concurrent chemotherapy No prior anthracycline therapy greater than 200 mg/m2 Endocrine therapy: Not specified Radiotherapy: No radiotherapy within the past 4 weeks No concurrent radiotherapy No prior radiotherapy to the whole abdomen Surgery: Prior surgery allowed
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
Vincent T. Lombardi Cancer Research Center, Georgetown University
Washington D.C., United StatesOpen Vincent T. Lombardi Cancer Research Center, Georgetown University in Google Maps