A Phase I Trial of Melphalan and Thiotepa Followed by Autologous or Syngeneic Peripheral Blood Stem Cell (PBSC) Rescue in Patients With a Complete Response Following Standard Therapy for Stage III/IV Epithelial Ovarian Cancer
filgrastim
+ melphalan
+ thiotepa
Urogenital Diseases+21
+ Genital Diseases
+ Adnexal Diseases
Treatment Study
Summary
Study start date: January 1, 1997
Actual date on which the first participant was enrolled.OBJECTIVES: I. Assess the toxic effects of combined high dose melphalan and thiotepa chemotherapy followed by stem cell rescue in patients with stage III or IV ovarian epithelial cancer in complete remission. II. Determine the maximum tolerated dose of thiotepa that can be given with melphalan in these patients. III. Evaluate the interpatient blood level variability and pharmacokinetics of melphalan given intravenously. OUTLINE: This is a dose escalation study of thiotepa. Patients receive cytoreduction and mobilization of peripheral blood stem cells (PBSC) with filgrastim (G-CSF) and cyclophosphamide/paclitaxel, cyclophosphamide/etoposide or cyclophosphamide/etoposide/cisplatin within 30-90 days of last dose of standard therapy. PBSC are then collected. Patients then receive melphalan IV over 30 minutes on days -6 and -5 and thiotepa IV over 2 hours on days -4 and -3. PBSC are reinfused on day 0. G-CSF is administered on days 0-21. Cohorts of 5-15 patients each receive escalating doses of thiotepa until the maximum tolerated dose (MTD) is reached. The MTD is determined as the dose at which 2-5 of 4-15 patients experience dose limiting toxicity. Patients are followed at 100 days, then at 6, 12, and 24 months. PROJECTED ACCRUAL: A total of 30-45 patients will be accrued for this study over 2 years.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.45 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.From 18 to 60 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/IV ovarian epithelial cancer in first or second clinical complete remission after receiving a minimum of 4-10 courses of chemotherapy consisting of paclitaxel and either cisplatin or carboplatin Ovarian epithelial cancer of following histologic types: Serous adenocarcinoma Mucinous adenocarcinoma Clear cell adenocarcinoma Transitional cell Adenocarcinoma N.O.S. Endometrioid adenocarcinoma Undifferentiated carcinoma Mixed epithelial carcinoma Malignant Brenner's Tumor Remission stability maintained for at least 4 weeks Protocol therapy must begin 30-90 days after last dose of standard therapy No active pleural or pericardial effusion No prior/concurrent brain metastasis or carcinoid meningitis PATIENT CHARACTERISTICS: Age: 18 to 60 Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin less than 1.5 times the upper limit of normal (ULN) SGOT or SGPT less than 2.0 times ULN Albumin greater than 2.0 g/dL Renal: Creatinine clearance greater than 60 mL/min Cardiovascular: Ejection fraction greater than 45% by MUGA Pulmonary: If history of smoking or abnormal lung function, Diffusion capacity greater than 50% (corrected) A-a gradient less than 20 Other: No history of hemorrhagic cystitis No second malignancy within the last 5 years except basal cell skin cancer HIV negative No chronic active hepatitis B No hepatitis C No history of Aspergillus infection PRIOR CONCURRENT THERAPY: Biologic therapy: No prior stem cell transplant Chemotherapy: Prior chemotherapy consisting of paclitaxel and either cisplatin or carboplatin Endocrine therapy: Not specified Radiotherapy: No prior radiation therapy for malignancy (excluding chest wall radiation therapy for breast cancer) Surgery: Not specified
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
Fred Hutchinson Cancer Research Center
Seattle, United StatesOpen Fred Hutchinson Cancer Research Center in Google Maps