Trial Information

A Phase I Trial of Sequential High Dose Chemotherapy Regimens Followed by Autologous or Syngeneic Peripheral Blood Stem Cell (PBSC) Rescue in Patients With Persistent Stage III/IV Ovarian Cancer

OBJECTIVES: I. Establish the feasibility of treating patients with persistent or platinum
refractory stage III or IV ovarian cancer with sequential high dose chemotherapy followed by
peripheral blood stem cell rescue. II. Determine the maximum tolerated dose of thiotepa that
can be given in such approach.

OUTLINE: This is a dose escalating study of thiotepa. Initial cytoreduction and mobilization
of peripheral blood stem cells (PBSC) are conducted with FHCRC protocol 506.3
(cyclophosphamide and paclitaxel) or 506.3 (cyclophosphamide and etoposide). PBSC from
syngeneic twins are collected according to FHCRC protocol 753.0. Patients then undergo
leukapheresis. Patients with remaining bulky disease (greater than 2 cm) after
cytoreduction/mobilization may undergo surgical debulking. High dose chemotherapy begins
30-40 days after the last chemotherapy in the cytoreduction/mobilization regimen. Patients
receive mitoxantrone IV infusion over 15 minutes on days -7 and -5. Thiotepa IV is
administered on days -4 and -3. Peripheral blood stem cell (PBSC) infusion occurs on day 0.
60-90 days later, melphalan IV is administered over 60 minutes on day -3. Patients undergo
PBSC infusion on day 0. Patients are entered in cohorts of 3. In the absence of
dose-limiting toxicity (DLT), subsequent cohorts of 3 patients each receive escalating doses
of thiotepa on the same schedule. If DLT is observed in 2 of 3 patients, then the next
cohort of patients each receive treatment at the next lower dose level. Once 12 patients are
treated at a particular dose level, then this dose is declared the maximum tolerated dose.
After engraftment following melphalan, patients receive oral tamoxifen twice a day for up to
5 years or until relapse. Patients are followed every 3 months for the first year, every 6
months for the next 4 years, then annually.

PROJECTED ACCRUAL: 20-30 patients will be accrued in 2 years.