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

Sponsored by:	International Breast Cancer Study Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00022516

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Drug: CAF regimen Drug: CMF regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: epirubicin hydrochloride Drug: fluorouracil Drug: methotrexate Procedure: adjuvant therapy	Phase III

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Surgery

Drug Information available for: Cyclophosphamide Fluorouracil Methotrexate Doxorubicin Doxorubicin hydrochloride Epirubicin hydrochloride Epirubicin Myocet

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control
Official Title:	Maintenance Chemotherapy In Hormone Non-Responsive Breast Cancer, Assessment of Vascular Endothelial Growth Factor (VEGF), Soluble Her2 Protein (NRP, HER2-ECD) and Vascular Cellular Adhesion Molecule-1 (VCAM-1) in Serum Samples

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Disease-free survival [ Designated as safety issue: No ]
Overall survival and systemic disease-free survival [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Quality of life [ Designated as safety issue: No ]

Estimated Enrollment:	990
Study Start Date:	November 2000

Detailed Description:

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.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, menopausal status (pre vs post), and approved induction chemotherapy (doxorubicin and cyclophosphamide vs other agents). Patients are randomized to one of two treatment arms.

Arm I: Patients receive one of the following approved adjuvant induction chemotherapy regimens:
- AC comprising doxorubicin and cyclophosphamide IV on day 1 every 21 days for 4 courses followed by paclitaxel IV or docetaxel 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 followed by paclitaxel IV or docetaxel IV on day 1 every 21 days for 4 courses
- FAC comprising cyclophosphamide, doxorubicin, and fluorouracil IV on days 1 every 21 days for 4 courses
- Doxorubicin every 21 days for 4 courses followed by CMF comprising cyclophosphamide IV, methotrexate IV, and fluorouracil IV on days 1 and 8 every 28 days for 4 courses
- AC OR EC and paclitaxel IV with filgrastim (G-CSF) every 14 days for 4 courses
- FEC comprising cyclophosphamide IV, epirubicin IV and fluorouracil IV on day 1 every 21 days for 3 courses followed by docetaxel IV on day 1 every 21 days for 3 courses
- TAC comprising docetaxel, doxorubicin, and cyclophosphamide IV on day 1 every 21 days for 6 courses
- AT comprising doxorubicin IV and docetaxel IV every 21 days for 3 courses followed by CMF for 3 courses
Arm II: Patients receive adjuvant induction chemotherapy as in arm I. Beginning within 56 days after the first day of the last course of induction chemotherapy, patients receive CM (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.

Patients with HER2-positive primary breast cancer may also receive trastuzumab (Herceptin) during or following induction, and/or during and following CM.

Quality of life is assessed at baseline, at the beginning of each course of induction chemotherapy, and at months 9, 12, 18, and 24.

Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: Approximately 900 patients will be accrued for this study within 5 years.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed stage I, II, or III breast cancer
- T1-3, N0-2, M0
  - Patients with sentinel node biopsy positive disease must have undergone axillary dissection
  - Tumor must be confined to the breast without detected metastases elsewhere
- 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
Must have undergone prior total mastectomy OR breast-conserving procedure (e.g., lumpectomy, quadrantectomy, or partial mastectomy with negative margins)
- Patients must begin or have begun induction chemotherapy within 8 weeks after definitive surgery
Negative surgical margins
Axillary clearance with at least 6 lymph nodes examined OR
Negative sentinel node biopsy OR
Positive lymph nodes and unsuitable for taxane-based chemotherapy
Known HER2 status by immunohistochemistry or fluorescence in situ hybridization
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 3,000/mm3
Platelet count greater than 100,000/mm3

Hepatic:

See Disease Characteristics
Bilirubin less than 2.0 mg/dL
ALT less than 1.5 times upper limit of normal OR
AST less than 60 IU/L

Renal:

Creatinine less than 1.2 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:

Prior trastuzumab (Herceptin) allowed

Chemotherapy:

See Disease Characteristics
No prior adjuvant or neoadjuvant chemotherapy for breast cancer

Endocrine therapy:

No prior endocrine therapy for breast cancer or prevention
No prior tamoxifen or raloxifene for breast cancer

Radiotherapy:

No prior radiotherapy for breast cancer except primary irradiation

Surgery:

See Disease Characteristics

Other:

No prior preventative therapy for breast cancer

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00022516

Show 36 Study Locations

Sponsors and Collaborators

International Breast Cancer Study Group

Investigators

Study Chair:

Marco Colleoni, MD

European Institute of Oncology

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000068827, IBCSG-22-00, EU-20119, EUDRACT-2005-005666-36
Study First Received:	August 10, 2001
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00022516 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Study placed in the following topic categories:

Antimetabolites
Immunologic Factors
Skin Diseases
Adjuvants, Immunologic
Breast Neoplasms
Adhesions
Cyclophosphamide
Folic Acid Antagonists
Endothelial Growth Factors
Immunosuppressive Agents
Epirubicin

Hormones
Doxorubicin
Folic Acid
Anti-Bacterial Agents
Fluorouracil
Methotrexate
Mitogens
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Breast Diseases

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Cyclophosphamide
Antibiotics, Antineoplastic
Neoplasms by Site
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents
Alkylating Agents

Nucleic Acid Synthesis Inhibitors
Breast Diseases
Skin Diseases
Breast Neoplasms
Enzyme Inhibitors
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Epirubicin
Doxorubicin
Pharmacologic Actions
Neoplasms
Fluorouracil
Myeloablative Agonists
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on May 06, 2009