Clinical trial NCT00002755: Standard Chemotherapy Compared With High-Dose Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Women With Breast Cancer
Official title: PROSPECTIVE RANDOMISED EVALUATION OF HIGH-INTENSITY CHEMOTHERAPY WITH PERIPHERAL BLOOD PROGENITOR SUPPORT IN PATIENTS WITH HIGH RISK BREAST CANCER
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage II breast cancer
stage IIIA breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-08-24
Enrollment: 600
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
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. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known which treatment regimen is more effective for breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of standard cyclophosphamide, methotrexate, and fluorouracil with that of high-dose combination chemotherapy plus peripheral stem cell transplantation in treating women who have stage II or stage IIIA breast cancer.

Detailed description: OBJECTIVES: I. Compare the efficacy of high dose cyclophosphamide and thiotepa with peripheral blood stem cell support vs conventional cyclophosphamide, methotrexate, and fluorouracil (CMF), both following doxorubicin induction, in women with high risk breast cancer.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by the number of positive axillary nodes (4-9 vs at least 10) and by center. Patients are randomized to one of two treatment arms. Arm I: Patients receive induction therapy consisting of doxorubicin IV every 3 weeks for 4 courses followed by consolidation therapy consisting of cyclophosphamide IV, methotrexate IV, and fluorouracil IV every 3 weeks for 8 courses. At week 4 of consolidation therapy, patients receive radiotherapy to the breast, chest wall, and axilla over 3-5 weeks or as appropriate. Following recovery from consolidation therapy, patients receive maintenance therapy consisting of oral tamoxifen daily for 5 years. Arm II: Patients receive induction therapy as in arm I followed by consolidation therapy consisting of stem cell mobilization with high dose cyclophosphamide IV over 2 hours and filgrastim (G-CSF) subcutaneously beginning 24 hours after cyclophosphamide and continuing until blood counts recover. At 13-28 days following peripheral blood stem cell (PBSC) collection and/or autologous bone marrow collection, patients undergo chemoablation consisting of thiotepa IV and cyclophosphamide IV continuously over 4 days followed 72 hours later by PBSC infusion with or without autologous bone marrow. Following hematologic recovery, patients receive radiotherapy and maintenance therapy as in arm I. Patients are followed every 6 months for 2 years, then annually.

PROJECTED ACCRUAL: More than 600 patients will be accrued for this study over 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically confirmed stage II or IIIA breast cancer with at least 4 positive axillary nodes Definitive resection required, preferably within 4 weeks prior to entry No overt residual axillary nodal carcinoma after surgery Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: Over 18 Sex: Female Menopausal status: Not specified Performance status: ECOG 0 or 1 Hematopoietic: Absolute neutrophil count greater than 1,500/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 9 g/dL PT and aPTT normal Hepatic: Bilirubin normal (unless benign congenital hyperbilirubinemia) Normal liver biopsy required in patients with active hepatitis B or C Renal: Creatinine normal Cardiovascular: No active heart disease Normal wall motion on MUGA or echocardiogram Other: Adequate nutritional status (i.e., more than 1,000 calories/day orally) HIV negative No serious medical or psychiatric disease No second malignancy except: Basal cell skin cancer Carinoma in situ of the cervix Not pregnant Negative pregnancy test

PRIOR CONCURRENT THERAPY: At least 2 weeks since major surgery

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: St. Vincent's Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's NHS Trust
state: England
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Hampstead, London
country: United Kingdom
facility: Royal Free Hospital
state: England
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
state: England
city: Huddersfield, West Yorks
country: United Kingdom
facility: Huddersfield Royal Infirmary
state: England
city: Leeds
country: United Kingdom
facility: St. James's Hospital
state: England
city: London
country: United Kingdom
facility: St. George's Hospital
state: England
city: London
country: United Kingdom
facility: Middlesex Hospital- Meyerstein Institute
state: England
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle General Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
state: England
city: Southampton
country: United Kingdom
facility: Royal South Hants Hospital
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson Oncology Centre
state: Scotland
city: Glasgow
country: United Kingdom
facility: Royal Infirmary
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Hospital
state: Wales
Study officials:
affiliation: Edinburgh Cancer Centre at Western General Hospital
name: Robert C.F. Leonard, MD, BS, MB
role: STUDY_CHAIR
References: