Radiation Therapy in Treating Women Who Have Undergone Surgery for Early-Stage Invasive Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase III Study of Regional Radiation Therapy in Early Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005957
• Other study ID #: MA20
• Secondary ID: CAN-NCIC-MA20NSA
• Status: Completed
• Phase: N/A
• Start date: March 9, 2000
• Est. completion date: April 19, 2017

Study information

• Verified date: March 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Radiation to the tumor site and surrounding area may kill more tumor cells. It is not yet known if radiation therapy to the breast alone following surgery is more effective than radiation therapy to the breast plus surrounding tissue in treating invasive breast cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy to the breast alone to see how well it works compared to radiation therapy to the breast plus surrounding tissue in treating women who have undergone surgery for early-stage invasive breast cancer.

Description:

OBJECTIVES:

• Compare the overall survival, disease-free survival, isolated local regional disease-free survival, and distant disease-free survival in women with previously resected, early stage, invasive breast cancer treated with breast radiotherapy with or without regional radiotherapy.

• Compare the toxic effects of these regimens in these patients.

• Compare the quality of life of patients (in certain participating centers) treated with these regimens.

• Compare the cosmetic outcomes in patients (in certain participating centers) 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 more than 3), number of axillary nodes removed (<10, > or equal to 10); type of chemotherapy (anthracycline containing vs other vs none), hormonal therapy (yes vs no), number of axillary lymph nodes excised*, and participating center. Patients are randomized to one of two treatment arms.

NOTE: * Patients with a negative sentinel node dissection with or without an axillary dissection will be stratified according to the total number of nodes removed

• Arm I: Patients undergo standard breast radiotherapy alone 5 days a week for 5 weeks in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients undergo breast and regional radiotherapy 5 days a week for 5 weeks in the absence of disease progression or unacceptable toxicity.

Radiotherapy in both arms begins as soon as possible after randomization. Radiotherapy must begin within 8 weeks after completion of adjuvant IV chemotherapy, unless radiotherapy is administered concurrently with chemotherapy (i.e., cyclophosphamide, methotrexate, and fluorouracil [CMF]), or within 16 weeks after the last breast surgery for patients treated with hormonal therapy alone.

Quality of life is assessed (in patients in certain participating centers) within 2 weeks prior to randomization, during the last week of radiotherapy, at 3 and 9 months after completion of radiotherapy, and then annually until first distant disease recurrence.

Cosmetic outcome is assessed (in patients in certain participating centers) within 2 weeks prior to randomization, and then at 3 and 5 years after completion of radiotherapy or until first distant disease recurrence.

Patients are followed at 3, 6, and 9 months, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 1,822 patients will be accrued for this study within approximately 4 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1832
• Est. completion date: April 19, 2017
• Est. primary completion date: November 20, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically proven invasive carcinoma of the breast

• No evidence of T4, N2-3, or M1 disease prior to surgery

• Node positive or high-risk node negative

• Prior breast-conserving therapy (BCT) (e.g., lumpectomy, partial mastectomy, or segmental mastectomy) and axillary node dissection or sentinel node biopsy required and must be a candidate for breast radiotherapy after BCT

• Normally patients should have microscopically clear resection margins and those with positive margins should undergo reexcision

• Patients with microscopically focally positive margins (defined as no greater than 3 times high power fields) are candidates for breast radiotherapy plus a boost to the lumpectomy site

• Patients with prior sentinel node dissection eligible if node negative, but still meet high-risk criteria

• If node positive, then a level I and II axillary dissection must be performed

• No evidence of residual disease in axilla after dissection

• Must be treated with currently accepted adjuvant systemic chemotherapy and/or hormonal therapy

• High risk of regional and systemic recurrence due to one of the following:

• Pathologically positive axillary lymph nodes

• Pathologically negative axillary lymph nodes with one of the following:

• Primary tumor greater than 5 cm

• Primary tumor greater than 2 cm and less than 10 axillary lymph nodes excised and one of the following:

• Estrogen receptor negative

• Skarf-Bloom-Richardson grade 3

• Lymphovascular invasion

• Hormone receptor status:

• Estrogen and progesterone receptor status known

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Sex:

• Female

Menopausal status:

• Premenopausal or postmenopausal

Performance status:

• ECOG 0-2

Life expectancy:

• At least 5 years

Hematopoietic:

• Not specified

Hepatic:

• SGOT and/or SGPT no greater than 3 times upper limit of normal (ULN)*

• Alkaline phosphatase no greater than 3 times ULN* NOTE: * Patients with laboratory values greater than 3 times ULN may still be eligible if no metastatic disease by imaging examinations

Renal:

• No serious nonmalignant renal disease

Cardiovascular:

• No serious nonmalignant cardiovascular disease

Pulmonary:

• No serious nonmalignant pulmonary disease

Other:

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No other serious nonmalignant disease (e.g., systemic lupus erythematosus or scleroderma) that would preclude definitive surgery or radiotherapy

• No other malignancy except:

• Nonmelanomatous skin cancer

• Carcinoma in situ of the cervix or endometrium

• Contralateral noninvasive breast cancer (unless prior radiotherapy to the contralateral breast)

• Invasive carcinoma of the cervix, endometrium, colon, thyroid, or melanoma that was curatively treated at least 5 years prior to study participation

• No psychiatric or addictive disorder that would preclude informed consent or study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics

• Concurrent standard adjuvant chemotherapy allowed

Endocrine therapy:

• See Disease Characteristics

• Concurrent standard adjuvant hormonal therapy allowed

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Radiation:
• Standard Breast Irradiation
Standard Breast Irradiation - A dose of 5000 cGy in 25 fractions at a rate of 200 cGy per day, 5 days a week for 5 weeks will be prescribed to the standard tangent fields.
• Breast Radiation plus Regional Radiation
Breast Radiation plus Regional Radiation - A dose of 5000 cGy in 25 fractions at a rate of 200 cGy per day, 5 days a week for 5 weeks will be prescribed to the modified wide tangent fields.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	QEII Health Sciences Center	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Grand River Regional Cancer Centre	Kitchener	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	The Vitalite Health Network - Dr. Leon Richard	Moncton	New Brunswick
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	McGill University - Dept. Oncology	Montreal	Quebec
Canada	Ottawa Health Research Institute - General Division	Ottawa	Ontario
Canada	CHA-Hopital Du St-Sacrement	Quebec City	Quebec
Canada	CHUQ-Pavillon Hotel-Dieu de Quebec	Quebec City	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Atlantic Health Sciences Corporation	Saint John	New Brunswick
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	Niagara Health System	St. Catharines	Ontario
Canada	Dr. H. Bliss Murphy Cancer Centre	St. John's	Newfoundland and Labrador
Canada	Northeast Cancer Center Health Sciences	Sudbury	Ontario
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario
Canada	Odette Cancer Centre	Toronto	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	BCCA - Vancouver Island Cancer Centre	Victoria	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba

Sponsors (7)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	National Cancer Institute (NCI), North Central Cancer Treatment Group, NSABP Foundation Inc, Radiation Therapy Oncology Group, SWOG Cancer Research Network, Trans Tasman Radiation Oncology Group

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Whelan TJ, Olivotto IA, Parulekar WR, Ackerman I, Chua BH, Nabid A, Vallis KA, White JR, Rousseau P, Fortin A, Pierce LJ, Manchul L, Chafe S, Nolan MC, Craighead P, Bowen J, McCready DR, Pritchard KI, Gelmon K, Murray Y, Chapman JA, Chen BE, Levine MN; MA — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Duration of study	10 years
Secondary	Disease-free Survival	Disease-free survival (including locoregional and distant disease)	10 years