Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Persistent or Platinum Refractory Stage III or IV Ovarian Cancer

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00003080

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: endocrine-modulating drug therapy Drug: melphalan Drug: mitoxantrone hydrochloride Drug: tamoxifen citrate Drug: thiotepa Procedure: peripheral blood stem cell transplantation	Phase 1

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

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 Start Date :

Sep 1, 1996

Actual Primary Completion Date :

May 1, 2001

Actual Study Completion Date :

May 1, 2001

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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