Combination Chemotherapy After Surgery in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer (22-00)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
International Breast Cancer Study Group
ClinicalTrials.gov Identifier:
NCT00022516
First received: August 10, 2001
Last updated: March 12, 2014
Last verified: March 2014
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Low-dose Cytotoxics as "Anti-angiogenesis Treatment" Following Adjuvant Induction Chemotherapy for Patients With ER-negative and PgR-negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by International Breast Cancer Study Group:

Primary Outcome Measures:
  • Disease-free survival [ Time Frame: Estimated 10 years after last patient in ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival and systemic disease-free survival [ Time Frame: Estimated 10 years after last patient in ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Two years after randomization ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: Estimated 10 years after last patient in ] [ Designated as safety issue: No ]

Estimated Enrollment: 1080
Study Start Date: November 2000
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Induction chemotherapy
Approved induction CT regimen after randomization.
Drug: CAF regimen Drug: CMF regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: epirubicin hydrochloride Drug: fluorouracil Drug: methotrexate Procedure: adjuvant therapy
Experimental: Induction chemotherapy followed by CM maintenance
Approved induction chemotherapy followed by 12 months of CM maintenance.
Drug: CAF regimen Drug: CMF regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: epirubicin hydrochloride Drug: fluorouracil Drug: methotrexate Procedure: adjuvant therapy

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

  Hide Study Locations
Locations
Australia, New South Wales
Tweed Heads Hospital
Tweed Heads, New South Wales, Australia, 2485
Australia, South Australia
Queen Elizabeth Hospital
Adelaide, South Australia, Australia, 5011
Australia, Victoria
Box Hill Hospital
Box Hill, Victoria, Australia, 3128
Maroondah Hospital
East Ringwood, Victoria, Australia, 3135
Murray Valley Private Hospital and Cancer Treatment Centre
Wodonga, Victoria, Australia, 3690
Australia
Christchurch Hospital
Christchurch, Australia, 1
Belgium
CHU Liege - Domaine Universitaire du Sart Tilman
Liege, Belgium, B-4000
Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil, 90035-003
Chile
Centro de Estudios Oncologicos Santiago
Santiago, Chile
Fundacion Arturo Lopez Perez
Santiago, Chile, 29
Hospital Clinico Universidad de Chile
Santiago, Chile
Hospital Clinico San Borja Arriaran
Santiago, Chile
Hospital Carlos Van Buren
Valparaiso, Chile
Hungary
National Institute of Oncology - Budapest
Budapest, Hungary, 1122
Italy
Ospedali Riuniti di Bergamo
Bergamo, Italy, 24100
Ospedale degli Infermi - ASL 12
Biella, Italy, 13900
Ospedale Civile Ramazzini
Carpi, Italy, 41012
Ospedale Alessandro Manzoni
Lecco, Italy, 23900
Ospedale San Paolo
Milan, Italy, 20142
European Institute of Oncology
Milano, Italy, 20141
Azienda Ospedaliera di Padova
Padova, Italy, 35128
Ospedale Civile Rimini
Rimini, Italy, 47900
Ospedale Sant' Eugenio
Rome, Italy, 00144
Policlinico Universitario Udine
Udine, Italy, 33100
Nigeria
University of Ibadan Health Center
Ibadan, Nigeria
Peru
Instituto Nacional de Enfermedades Neoplasicas
Lima, Peru, 34
Romania
Institutul Oncologic - Universitatea de Medicina
Cluj-Napoca, Romania, 3400
South Africa
Sandton Oncology Centre
Johannesburg, South Africa, 2121
Switzerland
Kantonsspital Aarau
Aarau, Switzerland, CH-5001
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Bellinzona, Switzerland, CH-6500
Inselspital Bern
Bern, Switzerland, CH-3010
Kantonsspital Graubuenden
Chur, Switzerland, CH-7000
FMH Onkologie/Haematologie
Rheinfelden, Switzerland, 4310
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Regionalspital
Thun, Switzerland, 3600
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
Sponsors and Collaborators
International Breast Cancer Study Group
Investigators
Study Chair: Marco Colleoni, MD European Institute of Oncology
  More Information

Additional Information:
No publications provided

Responsible Party: International Breast Cancer Study Group
ClinicalTrials.gov Identifier: NCT00022516     History of Changes
Other Study ID Numbers: CDR0000068827, IBCSG-22-00, EU-20119, EUDRACT-2005-005666-36
Study First Received: August 10, 2001
Last Updated: March 12, 2014
Health Authority: Switzerland: Swissmedic
Romania: National Medicines Agency
Belgium: Federal Agency for Medicinal Products and Health Products
Nigeria: The National Agency for Food and Drug Administration and Control
Italy: The Italian Medicines Agency
Sweden: Medical Products Agency

Keywords provided by International Breast Cancer Study Group:
stage IA breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IB breast cancer
estrogen receptor-negative breast cancer
progesterone receptor-negative breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Methotrexate
Doxorubicin
Epirubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on April 17, 2014