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

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
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 :	September 1996
Actual Primary Completion Date :	May 2001
Actual Study Completion Date :	May 2001

Arms and Interventions

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Outcome Measures

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Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Study Chair:	Leona A. Holmberg, MD, PhD	Fred Hutchinson Cancer Research Center

More Information

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ClinicalTrials.gov Identifier:	NCT00003080 History of Changes
Other Study ID Numbers:	1144.00; FHCRC-1144.00; NCI-G97-1329; CDR0000065775 ( Registry Identifier: PDQ )
First Posted:	April 14, 2004
Last Update Posted:	September 15, 2010
Last Verified:	September 2010

Keywords provided by Fred Hutchinson Cancer Research Center:

stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; recurrent ovarian epithelial cancer

Additional relevant MeSH terms:

Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Melphalan; Thiotepa; Tamoxifen; Mitoxantrone

Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bone Density Conservation Agents