Low-dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-negative Early Breast Cancer

Breast Cancer Clinical Trial

— 22-00  

Official title:

Low-dose Cytotoxics as "Anti-angiogenesis Treatment" Following Adjuvant Induction Chemotherapy for Patients With ER-negative and PgR-negative Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00022516
• Other study ID #: CDR0000068827
• Secondary ID: IBCSG-22-002005-
• Status: Active, not recruiting
• Phase: Phase 3
• First received: August 10, 2001
• Last updated: November 6, 2015
• Start date: November 2000
• Est. completion date: December 2020

Study information

• Verified date: November 2015
• Source: International Breast Cancer Study Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: SwissmedicRomania: National Medicines AgencyBelgium: Federal Agency for Medicinal Products and Health ProductsNigeria: The National Agency for Food and Drug Administration and ControlItaly: The Italian Medicines AgencySweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

This randomized, phase III trial was designed to test the efficacy of a low-dose chemotherapy-maintenance regimen, hypothesized to have anti-angiogenic activity, administered following standard chemotherapy in patients with early breast cancer whose tumors are hormone receptor negative.

Description:

PURPOSE:

• Evaluate a low-dose cyclophosphamide and methotrexate chemotherapy-maintenance regimen in early 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.

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 (anthracycline and cyclophosphamide vs other agents). Treatment duration is 12 months of low-dose chemotherapy-maintenance regimen (CM-maintenance) vs no chemotherapy-maintenance regimen (no-CM) following standard adjuvant chemotherapy. Patients are randomized to one of two treatment arms. Patients are followed every 6 months for 5 years, and yearly follow-up thereafter.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1086
• Est. completion date: December 2020
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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) with radiotherapy planned

• Patients must begin or have begun an approved induction chemotherapy regimen within 8 weeks after definitive surgery

• Negative surgical margins

• Axillary clearance with at least 6 lymph nodes examined OR negative sentinel node biopsy

• 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

Study Design

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Cyclophosphamide
50 mg/day orally continuously for 1 year
• Methotrexate
2.5 mg twice/day orally days 1 and 2 of every week for 1 year

Locations

Country	Name	City	State
Australia	Queen Elizabeth Hospital	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Christchurch Hospital	Christchurch
Australia	Maroondah Hospital	East Ringwood	Victoria
Australia	Tweed Heads Hospital	Tweed Heads	New South Wales
Australia	Murray Valley Private Hospital and Cancer Treatment Centre	Wodonga	Victoria
Belgium	CHU Liege - Domaine Universitaire du Sart Tilman	Liege
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	Rio Grande do Sul
Chile	Centro de Estudios Oncologicos Santiago	Santiago
Chile	Fundacion Arturo Lopez Perez	Santiago
Chile	Hospital Clinico San Borja Arriaran	Santiago
Chile	Hospital Clinico Universidad de Chile	Santiago
Chile	Hospital Carlos Van Buren	Valparaiso
Hungary	National Institute of Oncology - Budapest	Budapest
Italy	Ospedali Riuniti di Bergamo	Bergamo
Italy	Ospedale degli Infermi - ASL 12	Biella
Italy	Ospedale Civile Ramazzini	Carpi
Italy	Ospedale Alessandro Manzoni	Lecco
Italy	Ospedale San Paolo	Milan
Italy	European Institute of Oncology	Milano
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Ospedale Civile Rimini	Rimini
Italy	Ospedale Sant' Eugenio	Rome
Italy	Policlinico Universitario Udine	Udine
Nigeria	University of Ibadan Health Center	Ibadan
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
Romania	Institutul Oncologic - Universitatea de Medicina	Cluj-Napoca
South Africa	Sandton Oncology Centre	Johannesburg
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni	Bellinzona
Switzerland	Inselspital Bern	Bern
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	FMH Onkologie/Haematologie	Rheinfelden
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	Regionalspital	Thun
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
International Breast Cancer Study Group

Countries where clinical trial is conducted

Australia,  Belgium,  Brazil,  Chile,  Hungary,  Italy,  Nigeria,  Peru,  Romania,  South Africa,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival	Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to the first appearance of one of the following: invasive breast cancer recurrence at local, regional, or distant site, invasive contralateral breast cancer, second (non-breast) invasive cancer, or death without cancer event; or censored at date of last follow-up.	5-year estimates, reported at a median follow-up of 6.9 years	No
Secondary	Overall Survival	Estimated percentage of patients alive and disease-free at 5 years from randomization, where overall survival is defined as the time from randomization to death from any cause; or censored at date last known alive.	5-year estimates, reported at a median follow-up of 6.9 years	No
Secondary	Distant Recurrence-free Interval	Estimated percentage of patients alive and disease-free at 5 years from randomization, where distant recurrence-free Interval is defined as the time from randomization to invasive breast cancer recurrence at distant site, or invasive contralateral breast cancer; or censored at date of last follow up.	5-year estimates, reported at a median follow-up of 6.9 years	No
Secondary	Breast Cancer-free Interval	Estimated percentage of patients alive and disease-free at 5 years from randomization, where breast cancer-free interval is defined as the time from randomization to invasive breast cancer recurrence at local, regional, or distant site, or invasive contralateral breast cancer; or censored at date of last follow up.	5-year estimates, reported at a median follow-up of 6.9 years	No