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A Phase III Adjuvant Trial Of Sequenced EC + Filgrastim + Epoetin Alfa Followed By Paclitaxel Versus Sequenced AC Followed By Paclitaxel Versus CEF As Therapy For Premenopausal Women And Early Postmenopausal Women Who Have Had Potentially Curative Surgery For Node Positive Or High Risk Node Negative Breast Cancer


Phase 3
N/A
60 Years
Open (Enrolling)
Female
Breast Cancer

Thank you

Trial Information

A Phase III Adjuvant Trial Of Sequenced EC + Filgrastim + Epoetin Alfa Followed By Paclitaxel Versus Sequenced AC Followed By Paclitaxel Versus CEF As Therapy For Premenopausal Women And Early Postmenopausal Women Who Have Had Potentially Curative Surgery For Node Positive Or High Risk Node Negative Breast Cancer


OBJECTIVES:

Primary

- Compare the disease-free survival of premenopausal or early postmenopausal women with
previously resected node positive or high-risk node negative stage I-IIIB breast cancer
treated with cyclophosphamide, epirubicin, and fluorouracil vs cyclophosphamide,
epirubicin, filgrastim (G-CSF), and epoetin alfa followed by paclitaxel vs
cyclophosphamide and doxorubicin followed by paclitaxel.

Secondary

- Compare the overall survival of patients treated with these regimens.

- Compare the rate of toxic effects of these regimens in this patient population.

- Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
number of positive nodes (0 vs 1-3 vs 4-10 vs more than 10), type of prior surgery (total vs
partial mastectomy), and estrogen receptor status (positive vs negative). Patients are
randomized to one of three treatment arms.

- Arm I: Patients receive epirubicin IV and fluorouracil IV on days 1-8 and oral
cyclophosphamide on days 1-14. Treatment repeats every 28 days for 6 courses.

- Arm II: Patients receive epirubicin IV and cyclophosphamide IV on day 1 and filgrastim
(G-CSF) subcutaneously (SC) on days 2-13. Patients with a hemoglobin < 13.0 g/dL also
receive epoetin alfa SC once weekly beginning within 1 week after the start of therapy
and continuing as needed. Treatment repeats every 14 days for 6 courses. Beginning 21
days after completion of epirubicin and cyclophosphamide, patients receive paclitaxel
IV over 3 hours on day 1 and G-CSF and epoetin alfa as above. Treatment repeats every
21 days for 4 courses.

- Arm III: Patients receive doxorubicin IV over 15 minutes and cyclophosphamide IV over
15 minutes on day 1. Treatment repeats every 21 days for 4 courses.

Beginning 21 days after completion of doxorubicin and cyclophosphamide, patients receive
paclitaxel as in arm II. Treatment in all arms continues in the absence of disease
progression or unacceptable toxicity.

All receptor positive patients receive oral tamoxifen or anastrozole (if tamoxifen is
contraindicated) for 5 years after completion of chemotherapy.

Quality of life is assessed at baseline, day 1 of cycles 2, 3 4 and 6 (arm I), days 1 of
cycles 3 and and day 1 of cycles 1 and 4 of paclitaxel (arm II), day 1 of cycles 2 and 3,
day 1 of cycles 1 and 4 of paclitaxel, (arm III), 9 months, 12 months, and then annually
thereafter until 5 years

Patients are followed at 9 months, 12 months, every 4 months for 1 year, every 6 months for
3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 2,100 patients (700 per treatment arm) will be accrued for
this study within 4 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the breast that is potentially curable

- T0-4 (dermal involvement on pathology assessment only), N0-2, M0

- No clinical T4 disease

- Previously treated with one of the following:

- Total mastectomy and level II axillary node dissection

- Partial mastectomy and level II axillary node dissection with planned breast
radiotherapy after completion of adjuvant chemotherapy regimen*

- Patients with a positive sentinel node biopsy must undergo level II axillary
node dissection or sufficient nodal sampling

- If microscopic residual in situ or invasive disease is present at total or
partial mastectomy margins, planned radiotherapy must also include a boost to
the tumor bed

- No residual tumor in the axilla after dissection

- Axillary node positive

- Negative nodes allowed if the tumor is ≥ 1 cm and 1 or more of the following
criteria defining high-risk node-negative disease are met:

- Histological grade III or,

- Estrogen receptor negative or,

- Lymphatic/vascular invasion

- Hormone receptor status:

- Estrogen receptor status known

PATIENT CHARACTERISTICS:

Age:

- 60 and under

Sex:

- Female

Menopausal status:

- Pre- or postmenopausal

Performance status:

- ECOG 0-2

Life expectancy:

- At least 5 years

Hematopoietic:

- WBC ≥ 3,000/mm^3

- Platelet count ≥ 100,000/mm^3

Hepatic:

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

Renal:

- Creatinine ≤ 1.5 times ULN

Cardiovascular:

- LVEF ≥ limit of normal by MUGA or echocardiogram

- No arrhythmia requiring ongoing treatment

- No congestive heart failure

- No documented coronary artery disease

Other:

- No other malignancy except:

- Adequately treated basal cell or squamous cell skin cancer or carcinoma in situ
of the cervix

- Ductal or lobular carcinoma in situ that has been curatively treated by surgery
alone

- Other prior malignancies (except breast cancer) curatively treated more than 5
years prior to study entry

- No serious underlying medical illness or psychiatric or addictive disorder that would
preclude study compliance

- No known hypersensitivity to E. coli-derived products, mammalian-cell derived
products, or any study agents

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective non-hormonal contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No prior immunotherapy for breast cancer

- No concurrent pegfilgrastim or darbepoetin alfa (Arm II)

- Allowed on arms 1 and 3 if medically necessary

Chemotherapy:

- No prior chemotherapy for breast cancer

Endocrine therapy:

- No prior hormonal therapy for breast cancer

- No concurrent hormone replacement therapy

- No concurrent selective estrogen-receptor modulators (e.g., raloxifene for the
treatment or prevention of osteoporosis)

- No concurrent oral contraceptives (i.e., birth control pills)

- No other concurrent aromatase inhibitors

Radiotherapy:

- See Disease Characteristics

- No prior radiotherapy for breast cancer

Surgery:

- See Disease Characteristics

- No more than 12 weeks since prior total or partial mastectomy (including re-excision
of margins)

Other:

- At least 30 days since prior investigational drugs

- No other concurrent investigational drugs

- Concurrent bisphosphonates for the treatment or prevention of osteoporosis allowed

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease free survival

Outcome Time Frame:

15 years

Safety Issue:

No

Principal Investigator

Mark N. Levine, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Margaret and Charles Juravinski Cancer Centre

Authority:

Canada: Health Canada

Study ID:

MA21

NCT ID:

NCT00014222

Start Date:

December 2000

Completion Date:

December 2015

Related Keywords:

  • Breast Cancer
  • stage I breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • Breast Neoplasms

Name

Location

Staten Island University HospitalStaten Island, New York  10305
Our Lady of Mercy Medical CenterBronx, New York  10466
Oncology/Hematology Care, Inc.Cincinnati, Ohio  45219
Maine Center for Cancer Medicine and Blood DisordersScarborough, Maine  04074
Consultants in Blood Disorders and CancerLouisville, Kentucky  40207
Florida Oncology AssociatesOrange Park, Florida  32073
Duke University Medical CenterDurham, North Carolina  27710
Queens Medical Associates, PCFresh Meadows, New York  11365
Sparks-Arkansas Oklahoma Cancer Treatment CentreFort Smith, Arkansas  72901
Hematology Oncology Services of ArkansasLittle Rock, Arkansas  72205
Scripps Cancer CenterLa Jolla, California  92037
University of Colorado Cancer CentreAurora, Colorado  80010-0510
Greenwich Hospital - Bendheim Cancer CenterGreenwich, Connecticut  06830
Sibley Memorial Hospital, Oncology ResearchWashington, District of Columbia  20016
Comprehensive Cancer Care Centre at Boca RatonBoca Raton, Florida  33428
University of FloridaGainesville, Florida  32610-0277
The University of Chicago Medical CenterChicago, Illinois  60637-1470
Therapy Associates, Inc., Hematology/OncologyEvansville, Indiana  47715
Lexington Oncology Assts./Central Baptist HospitalLexington, Kentucky  40503
CHRISTUS Schumpert Medical Center - Hem/Onc ClinicShreveport, Louisiana  71101
Willis-Knighton Cancer CenterShreveport, Louisiana  71103-3
Maine General Medical CenterWaterville, Maine  04901
Suburban Hospital Cancer ProgramBethesda, Maryland  20817
Associates in Oncology/HematologyRockville, Maryland  20850
Saint Joseph Medical Center, Cancer Care ProgramTowson, Maryland  21204
Baystate Regional Cancer ProgramSpringfield, Massachusetts  01107
St. Luke's Cancer Care CentreDuluth, Minnesota  55802
University of Minnesota Cancer CentreMinneapolis, Minnesota  55455
Columbia-Capitol Comprehensive Care ClinicsJefferson City, Missouri  65109
Saint Louis University HospitalSt. Louis, Missouri  63110-0250
Creighton University Cancer CentreOmaha, Nebraska  68131
Nebraska Methodist HospitalOmaha, Nebraska  68114
Advanced Oncology AssociatesArmonk, New York  10504
Winthrop University Hospital Onc/HemMineola, New York  11501
Hematology Oncol. Associates RocklandNyack, New York  10960
University of RochesterRochester, New York  14642
ECU School of Medicine, Leo Jenkins Cancer CenterGreenville, North Carolina  27858
Pottstown Memorial Regional Cancer CentrePottstown, Pennsylvania  19464
Santee Hematology OncologySumter, South Carolina  29150
University Oncology and Hematology AssociatesChattanooga, Tennessee  37404
Lone Star Oncology Consultants, PAAustin, Texas  78759
Center for Oncology Research and TreatmentDallas, Texas  75230
Northern Utah AssociatesOgden, Utah  84403
Arlington-Fairfax Hematology Oncology P.C.Arlington, Virginia  22205