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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

Phase 1/Phase 2
18 Years
Not Enrolling
Ovarian Cancer

Thank you

Trial Information

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

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.

Inclusion 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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Gary Spitzer, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Lombardi Cancer Research Center


United States: Federal Government

Study ID:




Start Date:

December 1997

Completion Date:

January 2001

Related Keywords:

  • Ovarian Cancer
  • stage III ovarian epithelial cancer
  • stage IV ovarian epithelial cancer
  • recurrent ovarian epithelial cancer
  • Ovarian Neoplasms



Vincent T. Lombardi Cancer Research Center, Georgetown University Washington, District of Columbia  20007