A Phase 3 interventional study of filgrastim and CMF regimen in Breast Cancer, sponsored by ETOP IBCSG Partners Foundation. Completed at 11 sites in 2 countries. Open to female participants aged 16 Years to 65 Years. Per ClinicalTrials.gov, last updated 2013-04-04.
Sponsored by ETOP IBCSG Partners Foundation · Phase 3, Interventional, and Treatment
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.
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.
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This study's enrollment of 344 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
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DISEASE CHARACTERISTICS: Histologically proven breast carcinoma in one of the following categories: 10 or more involved axillary nodes 5 or more involved axillary nodes and either: Primary tumor estrogen receptor (ER)-negative (less than 10 femtomoles per milligram of cytosol protein) T3 tumor (regardless of ER status) Total mastectomy or breast-conserving procedure (lumpectomy or quadrantectomy) required within 6 weeks prior to randomization Tumor confined to breast and axillary nodes (T1a-c, T2, or T3, N1-2, M0 by the UICC staging system) The following conditions exclude entry: Satellite skin nodules distant from the primary tumor Supraclavicular node involvement Inoperable, matted axillary nodes Fixation of primary tumor to chest wall (excluding pectoralis major) Bilateral breast cancer (any mass in opposite breast unless biopsy-proven benign) Hot spots on bone scintigram (unless confirmed to be benign) Skeletal pain of unknown cause Hormone receptor status: ER status determination preferred, but not required
PATIENT CHARACTERISTICS: Age: 16-65 Sex: Women only Menopausal status: Any status Performance status: ECOG 0-2 Hematopoietic: WBC at least 4,000 Platelets at least 100,000 Hepatic: Bilirubin no greater than 1.1 mg/dL (20 micromoles/L) AST no greater than twice normal Renal: Creatinine no greater than 1.3 mg/dL (120 micromoles/L) Cardiovascular: Left ventricular ejection fraction greater than 50% by MUGA Other: No second malignancy except: Basal cell carcinoma Adequately treated carcinoma in situ of the cervix No significant nonmalignant disease that would preclude participation No psychiatric or addictive disorder that would compromise informed consent or participation No pregnant or nursing women Adequate contraception strongly advised for fertile women
PRIOR CONCURRENT THERAPY: No prior therapy for breast cancer other than surgery (see Disease Characteristics)
EC/AC x 4 followed by CMF x 3 and tamoxifen to 5 years after randomization.
Drug: CMF regimen · Drug: cyclophosphamide · Drug: doxorubicin hydrochloride · Drug: epirubicin hydrochloride · Drug: fluorouracil · Drug: methotrexate · Drug: tamoxifen citrate · Radiation: low-LET electron therapy · Radiation: low-LET photon therapy
High-dose EC x 3 supported by peripheral blood progenitor cells and tamoxifen to 5 years after randomization.
Biological: filgrastim · Drug: cyclophosphamide · Drug: mesna · Drug: tamoxifen citrate · Procedure: peripheral blood stem cell transplantation · Radiation: low-LET electron therapy · Radiation: low-LET photon therapy
Filgrastim 10 mg/kg/d sc for 6 days after randomization.
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.
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.
Doxorubicin 60 mg/m2 iv on day 1 of 21-day cycles of AC.
Epirubicin 90 mg/m2 iv on day 1 of 21-day cycles of EC.
5-fluorouracil 600 mg/m2 iv days 1 and 8 of 28-day cycles of CMF.
MESNA (7.2 gm/m2) on days 2 and 3 of 21-day cycles of dose-intensive EC.
Methotrexate 40 mg/m2 iv on days 1 and 8 of 28-day cycles of CMF.
Tamoxifen 20mg daily for 5 years or until relapse.
Peripheral blood progenitor cells (PBPC) infusion on day 5 of each 21-day cycle of dose-intensive EC.
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 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.
Disease-free survival.
Time from randomization to recurrence (including recurrence isolated to the breast), metastasis, appearance of a second primary tumor, or death from any cause, whichever occurs first.
Time frame: 16 years after randomization.
Overall survival.
Time from randomization to death from any cause.
Time frame: 16 years after randomization.
Toxicity.
Morbidity information was recorded using standard toxicity criteria.
Time frame: 5 years after randomization.
Quality of life.
Quality of life was assessed using standard International Breast Cancer Study Group instruments.
Time frame: 16 years after randomization.
This study is completed, as verified in Jul 2012. You cannot join it, but the record below documents what was studied.
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ETOP IBCSG Partners Foundation