Clinical trial NCT00003080: Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Persistent or Platinum Refractory Stage III or IV Ovarian Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Cancer
Keywords: stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian epithelial cancer
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-14
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically proven persistent or platinum refractory stage III/IV ovarian cancer

PATIENT CHARACTERISTICS: Age: 18 to 60 Performance status: Karnofsky 80-100% Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 1.5 mg/mL, unless history of Gilbert's disease SGOT or SGPT no greater than 2 times upper limit of normal Renal: Creatinine clearance at least 50 mg/mL No history of hemorrhagic cystitis Cardiovascular: No history of coronary artery disease No poorly controlled arrhythmia or myocardial infarction Left ventricle ejection fraction at least 50% Pulmonary: Diffusion capacity at least 50% Other: Not pregnant HIV negative No second malignancy in the last 5 years except basal carcinoma of the skin

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No history of allergy to any chemotherapy drugs Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Leona A. Holmberg, MD, PhD
role: STUDY_CHAIR
References: