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
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.
Primary Purpose: Treatment
Leona A. Holmberg, MD, PhD
Fred Hutchinson Cancer Research Center
United States: Federal Government
|Fred Hutchinson Cancer Research Center||Seattle, Washington 98109|