Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Persistent or Platinum Refractory Stage III or IV Ovarian Cancer
Condition: Ovarian Cancer
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation
      may allow the doctor to give higher doses of chemotherapy and kill more tumor cells.

      PURPOSE: Phase I trial to study the effectiveness of sequential chemotherapy followed by
      peripheral stem cell transplantation in treating patients with persistent or platinum
      refractory stage III or stage IV ovarian cancer.
    

Detailed description: 
      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.
    

Intervention name(s): endocrine-modulating drug therapy; melphalan; mitoxantrone hydrochloride; tamoxifen citrate; thiotepa; peripheral blood stem cell transplantation
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Procedure
Intervention MeSH terms: Tamoxifen; Melphalan; Thiotepa; Mitoxantrone
Primary purpose: Treatment
Keywords: stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; recurrent ovarian epithelial cancer