Combination Chemotherapy After Surgery in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective after surgery in treating breast cancer.

PURPOSE: Randomized phase III trial to compare different combination chemotherapy regimens in treating patients who have stage I, stage II, or stage III breast cancer.

Official Title

Phase III Randomized Study of Adjuvant Induction Chemotherapy With or Without Cyclophosphamide and Methotrexate as Maintenance Chemotherapy in Patients With Stage I, II, or III Breast Cancer

Conditions

Study Type

Interventional

Study Design

This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, menopausal status (pre vs post), and induction chemotherapy (doxorubicin and cyclophosphamide vs other agents). Patients are randomized to one of two treatment arms. Patients receive one of the following adjuvant induction chemotherapy regimens: Arm I: AC comprising doxorubicin and cyclophosphamide IV on day 1 every 21 days for 4 courses EC comprising epirubicin and cyclophosphamide IV on day 1 every 21 days for 4 courses CMF comprising oral cyclophosphamide once daily on days 1-14 and methotrexate and fluorouracil IV on days 1 and 8 every 28 days for 6 courses AC OR EC for 4 courses followed by CMF for 3 courses CEF comprising oral cyclophosphamide once daily on days 1-14 and epirubicin and fluorouracil IV on days 1 and 8 every 28 days for 6 courses CAF comprising oral cyclophosphamide once daily on days 1-14 and doxorubicin and fluorouracil IV on days 1 and 8 every 28 days for 6 courses Arm II: Patients receive adjuvant induction chemotherapy as in arm I. Beginning 28 days after the completion of induction chemotherapy, patients receive maintenance chemotherapy comprising oral cyclophosphamide once daily and oral methotrexate two times a day twice weekly for 1 year. Patients with breast-conserving surgery receive radiotherapy following completion of induction chemotherapy.Quality of life is assessed at baseline, at the beginning of each course of induction chemotherapy, and at months 6, 12, 18, 24, 36, 48, 60, and 72. Patients are followed every 6 months for 5 years and then annually thereafter.

Further Details

OBJECTIVES:- Determine the efficacy of adjuvant induction chemotherapy with or without cyclophosphamide and methotrexate as maintenance chemotherapy in patients with stage I, II, or III breast cancer. – Compare the disease-free survival, overall survival, and systemic disease-free survival of patients treated with these regimens. – Compare the toxic effects of these regimens in these patients. – Compare the quality of life of patients treated with these regimens.

Study Start

July 2005

Eligibility & Criteria

Genders Eligible for Study: Both CriteriaDISEASE CHARACTERISTICS:- Histologically confirmed stage I, II, or III breast cancer – T1-3, N0-1, M0 – T4 disease with minimal dermal invasion allowed – No T4 disease with ulceration of skin, infiltration of skin (except pathologically minimal dermal involvement), peau d’orange, or inflammatory breast cancer – No bilateral breast cancer (except in situ carcinoma) or suspicious mass in opposite breast that has not been proven benign – No distant metastases – No skeletal pain of unknown cause, elevated alkaline phosphatase, or bone scan showing hot spots that cannot be ruled out as metastases by x-ray, MRI, and/or CT – Prior total mastectomy OR breast-conserving procedure (e.g., lumpectomy, quadrantectomy, or partial mastectomy with negative margins) within past 6 weeks – Negative surgical margins – Axillary clearance with at least 8 lymph nodes examined OR – Negative sentinel node biopsy OR – Positive lymph nodes and unsuitable for taxane-based chemotherapy Hormone receptor status: – Estrogen and progesterone receptor negative – Less than 10% positive tumor cells by immunohistochemistry PATIENT CHARACTERISTICS:Age: Not specified Sex: Not specified Menopausal status: Premenopausal, defined as less than 6 months since last menstrual period (LMP) AND no prior bilateral ovariectomy AND not on estrogen replacement (OR under age 50) OR Postmenopausal, defined as prior bilateral ovariectomy OR more than 12 months since LMP without prior hysterectomy (OR age 50 and over) Performance status: Not specified Life expectancy: Not specified Hematopoietic: WBC greater than 4,000/mm3, Platelet count greater than 100,000/mm3 Hepatic: See Disease Characteristics- Bilirubin less than 1.17 mg/dL, ALT less than 1.5 times upper limit of normal OR AST less than 60 IU/L Renal: Creatinine less than 1.36 mg/dL Other: – Not pregnant or lactating within the past 6 months – Fertile patients must use effective barrier contraception – No other prior or concurrent malignancy except adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or contralateral or ipsilateral in situ breast carcinoma – No psychiatric or addictive disorders that would preclude study – No non-malignant systemic disease that would preclude study PRIOR CONCURRENT THERAPY:Biologic therapy: Not specified Chemotherapy: See Disease Characteristics- No prior adjuvant or neoadjuvant chemotherapy for breast cancer Endocrine therapy: No prior endocrine therapy for breast cancer, No prior tamoxifen or raloxifene for breast cancer Radiotherapy: No prior radiotherapy for breast cancer Surgery: See Disease Characteristics Other: No prior preventative therapy for breast cancer

Total Enrolment

Approximately 1,330 patients will be accrued for this study within 5 years.

Contact Details

Canberra Hospital, Garran, 2605, Australia; Recruiting Paul Craft, MD 61-2-6244-2220 paul.craft@act.gov.auCancer Therapy Centre at Liverpool Hospital, Liverpool, New South Wales, 2170, Australia; Recruiting Eugene Moylan 61-2-9828-5283 eugene.moyland@swsahs.nsw.gov.au Institute of Oncology at Prince of Wales Hospital, Randwick, New South Wales, 2031, Australia; Recruiting Michael L. Friedlander, MD, PhD, FRACP 61-2-9382-2606 m.friedlander@unsw.edu.au Newcastle Mater Misericordiae Hospital, Waratah, New South Wales, 2298, Australia; Recruiting John F. Forbes, MD, FRACS, MS, FRCS, MBBS 61-2-4985-0113 john.forbes@anzbctg.newcastle.edu.au Port Mcquarie Base Hospital, Port Macquarie, New South Wales, 2444, Australia; Recruiting Stephen Begbie 61-2-6580-1116 Royal Hospital for Women, Randwick, New South Wales, 2031, Australia; Recruiting John Eden, MD 61-2-9382-6777 j.eden@unsw.edu.au Royal North Shore Hospital, St. Leonards, New South Wales, 2065, Australia; Recruiting Helen Wheeler, MD 61-2-9926-7184 helonwheeler@bigpond.com.au St. George Hospital and Community Health Service, Sydney, New South Wales, 2217, Australia; Recruiting Paul L. de Souza, MD 61-2-9350-3910 p.desouza@unsw.edu.au Westmead Hospital, Wentworthville, New South Wales, 2145, Australia; Recruiting Paul R. Harnett, MD 61-2-9845-6954 Caboolture Hospital, Caboolture, Queensland, 4510, Australia; Recruiting W. G. Premaratne, MD, MS, FRCS, FRACS 61-7-5433-8846 Mater Private Clinic, South Brisbane, Queensland, 4101, Australia; Recruiting Kerry M. Taylor, MD, BS, FRACP 61-7-3840-8943 ktaylor@mater.org.au Princess Alexandra Hospital, Brisbane, Queensland, 4102, Australia; Recruiting Euan T. Walpole, MD 61-7-3240-2555 Euan_Walpolee@health.qld.gov.au Royal Brisbane and Women’s Hospital, Brisbane, Queensland, 4029, Australia; Recruiting Simon Durrant, MD 61-7-3636-8756 simon_durrant@health.qld.gov.au Townsville General Hospital, Townsville, Queensland, 4810, Australia; Recruiting P Donnelly, MD 61-7-4796-1634 Wesley Medical Centre, Auchenflower, Queensland, 4066, Australia; Recruiting C. Furnival, MD, FRCS, FRACS 61-7-3870-4422 Ashford Cancer Centre, Ashford, South Australia, 5035, Australia; Recruiting Dusan Kotasek, MD 61-8-8351-0211 dusan.kotasek@bigpond.com Queen Elizabeth Hospital, Adelaide, South Australia, 5011, Australia; Recruiting K. Patterson, MD 61-8-8222-6847 william.patterson@nwahs.sa.gov.au Launceston General Hospital, Launceston, Tasmania, 7250, Australia; Recruiting Contact Person 61-3-327-111 Royal Hobart Hospital, Hobart, Tasmania, 7000, Australia; Recruiting Raymond M. Lowenthal, MD 61-3-6222-8157 r.m.lowenthal@utas.edu.au Andrew Love Cancer Centre, Geelong, Victoria, 3220, Australia; Recruiting R. McLennan, MD 61-3-5226-7855 mclennan@pipeline.com.au Austin Hospital, Heidelberg, Victoria, 3084, Australia; Recruiting Mitchell Chipman, MD 61-3-9457-1029 drmpc@bigpond.com Box Hill Hospital, Box Hill, Victoria, 3128, Australia; Recruiting J. Chirgwin, MD 61-3-9895-3586 Cabrini Hospital, Malvern, Victoria, 3144, Australia; Recruiting Gary Edward Richardson, MD 61-3-9509-6988 gary.richardson@southeastoncology.com.au Frankston Hospital, Frankston, Victoria, 3199, Australia; Recruiting Vinod Ganju, MD 61-3-9784-7777 ganju@attglobal.net Murray Valley Private Hospital and Cancer Treatment Centre, Wodonga, Victoria, 3690, Australia; Recruiting Craig Underhill, MD, MBBS, FRACP 61-2-6055-3200 craig.underhill@bordermedonc.com.au Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia; Recruiting Guy C. Toner, MD, MBBS, FRACP 61-3-9656-1111 Royal Melbourne Hospital, Parkville, Victoria, 3050, Australia; Recruiting John P. Collins, MD 61-3-9349-4688 collins5@iprimus.com.au St. Vincent’s Hospital, Fitzroy, Victoria, 3065, Australia; Recruiting Raymond D. Snyder, MD 61-3-9288-3155 snyderrd@svhm.org.au Fremantle Hospital, Fremantle, Western Australia, 6160, Australia; Recruiting J. A. Davidson, MD 08-9431-2580 Mount Medical Centre, Perth, Western Australia, 6000, Australia; Recruiting Guy A. Van Hazel, MD 61-8-9481-3072 Royal Perth Hospital, Perth, Western Australia, 6000, Australia; Recruiting David Turner Ranson, MD 61-8-9224-2334 Sir Charles Gairdner Hospital Perth, Western Australia, 6009, Australia; Recruiting Michael J. Byrne, MRCP, MBBS, FRACP, MD 61-8-9346-3841