NCT00002784

High-Dose Combination Chemotherapy Plus Peripheral Stem Cell Transplantation Compared With Standard Combination Chemotherapy in Treating Women With High-Risk Breast Cancer

Randomized Trial of High-dose Epirubicin and Cyclophosphamide x 3 Supported by Peripheral Blood Progenitor Cells Versus Anthracycline and Cyclophosphamide x 4 Followed by Cyclophosphamide, Methotrexate, and 5-fluorouracil x 3 as Adjuvant Treatment for High Risk Operable Stage ii and Stage Iii Breast Cancer in Premenopausal and Young Postmenopausal (Less Than or Equal to 65 Yrs) Patients.

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 344 (actual)
• Sponsor: ETOP IBCSG Partners Foundation · Network
• Sex: Female
• Age: 16 Years – 65 Years
• Healthy volunteers: Not accepted

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 drugs and kill more tumor cells. It is not yet known if high-dose combination chemotherapy plus peripheral stem cell transplantation is more effective than standard combination chemotherapy for breast cancer. PURPOSE: Randomized phase III trial to compare high-dose combination chemotherapy plus peripheral stem cell transplantation with standard combination chemotherapy in treating women with stage II or stage III breast cancer.

Detailed description

OBJECTIVES: I. Compare the survival, disease-free survival, and systemic disease-free survival of women with high-risk, operable stage II/III breast cancer treated with three courses of dose-intensive epirubicin/cyclophosphamide (EC) supported by granulocyte colony-stimulating factor (G-CSF) and G-CSF-mobilized peripheral blood stem cells vs. standard EC followed by cyclophosphamide/methotrexate/fluorouracil. II. Compare the toxicity, duration of quality-adjusted time without symptoms and toxicity, and quality of life associated with these two treatments. III. Evaluate the cost effectiveness of these two treatments. OUTLINE: This is a randomized study. Patients are stratified by estrogen receptor status and menopausal status. Within 6 weeks of surgery, patients in the first group receive epirubicin (preferred) or doxorubicin plus cyclophosphamide every 3 weeks for 4 courses followed by conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) every 4 weeks for 3 courses. Patients in the second group undergo stem cell mobilization and harvest with granulocyte colony-stimulating factor (G-CSF) followed within 10 weeks of surgery by high-dose chemotherapy with epirubicin and cyclophosphamide followed by peripheral blood stem cell rescue and G-CSF. All patients receive adjuvant tamoxifen, and patients who underwent lumpectomy prior to entry are required to receive adjuvant radiotherapy (radiotherapy is optional for patients who underwent mastectomy prior to entry). Patients are followed every 3 months for 2 years, then q 6 months for 3 years, then yearly. PROJECTED ACCRUAL: 210 patients will be accrued over 4 years to provide 195 evaluable patients.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
BIOLOGICAL	filgrastim	Filgrastim 10 mg/kg/d sc for 6 days after randomization.
DRUG	CMF regimen	Cyclophosphamide 100 mg/m2 orally days 1 - 14, methotrexate 40 mg/m2 iv days 1 and 8, 5-fluorouracil 600 mg/m2 iv days 1 and 8. Repeat every 28 days.
DRUG	cyclophosphamide	For high-dose EC arm: cyclophosphamide 4 gm/m2 iv as 4 divided doses. For standard chemotherapy arm: cyclophosphamide 600 mg/m2 iv day 1 of 21-day EC cycles, and cyclophosphamide 100 mg/m2 orally on days 1-14 of 28-day CMF cycles.
DRUG	doxorubicin hydrochloride	Doxorubicin 60 mg/m2 iv on day 1 of 21-day cycles of AC.
DRUG	epirubicin hydrochloride	Epirubicin 90 mg/m2 iv on day 1 of 21-day cycles of EC.
DRUG	fluorouracil	5-fluorouracil 600 mg/m2 iv days 1 and 8 of 28-day cycles of CMF.
DRUG	mesna	MESNA (7.2 gm/m2) on days 2 and 3 of 21-day cycles of dose-intensive EC.
DRUG	methotrexate	Methotrexate 40 mg/m2 iv on days 1 and 8 of 28-day cycles of CMF.
DRUG	tamoxifen citrate	Tamoxifen 20mg daily for 5 years or until relapse.
PROCEDURE	peripheral blood stem cell transplantation	Peripheral blood progenitor cells (PBPC) infusion on day 5 of each 21-day cycle of dose-intensive EC.
RADIATION	low-LET electron therapy	Radiation therapy to the conserved breast is mandatory, to be carried out according to the prospectively defined guidelines of each participating institution; either after all chemotherapy or integrated into CMF as agreed per institution. Radiotherapy to the chest wall following mastectomy is optional according to the prospectively defined guidelines of each participating institution.
RADIATION	low-LET photon therapy	radiation therapy to the conserved breast is mandatory, to be carried out according to the prospectively defined guidelines of each participating institution; either after all chemotherapy or integrated into CMF as agreed per institution. Radiotherapy to the chest wall following mastectomy is optional according to the prospectively defined guidelines of each participating institution.

Timeline

• Start date: 1996-06-01
• Primary completion: 2011-08-01
• Completion: 2011-12-01
• First posted: 2004-07-29
• Last updated: 2013-04-04

Locations

11 sites across 2 countries: Australia, Switzerland