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

NCT ID: NCT00005957

Last Updated: 2023-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1832 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-03-09
• Study Completion Date: 2017-04-19

Brief 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.

Detailed 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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Breast Irradiation

Group Type: ACTIVE_COMPARATOR

Standard Breast Irradiation

Intervention Type: RADIATION

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

regional radiation therapy (to the ipsilateral supraclavicular, axillary and internal mammary nodes)

Group Type: EXPERIMENTAL

Breast Radiation plus Regional Radiation

Intervention Type: 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.

Interventions

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.

Intervention Type: RADIATION

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.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NSABP Foundation Inc

NETWORK

Sponsor Role: collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: collaborator

Trans Tasman Radiation Oncology Group

OTHER

Sponsor Role: collaborator

North Central Cancer Treatment Group

NETWORK

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy J. Whelan, MD

Role: STUDY_CHAIR

Margaret and Charles Juravinski Cancer Centre

David S. Parda

Role: STUDY_CHAIR

Allegheny Cancer Center at Allegheny General Hospital

Julia R. White, MD

Role: STUDY_CHAIR

Medical College of Wisconsin

Lori J. Pierce, MD

Role: STUDY_CHAIR

University of Michigan Rogel Cancer Center

Boon Chua, MD

Role: STUDY_CHAIR

Peter MacCallum Cancer Centre, Australia

Laura A. Vallow, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, Canada

Atlantic Health Sciences Corporation

Saint John, New Brunswick, Canada

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, Canada

QEII Health Sciences Center

Halifax, Nova Scotia, Canada

Northeast Cancer Center Health Sciences

Greater Sudbury, Ontario, 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

Ottawa Health Research Institute - General Division

Ottawa, Ontario, Canada

Niagara Health System

St. Catharines, Ontario, 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

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada

McGill University - Dept. Oncology

Montreal, Quebec, Canada

CHUQ-Pavillon Hotel-Dieu de Quebec

Québec, Quebec, Canada

CHA-Hopital Du St-Sacrement

Québec, Quebec, Canada

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Countries

Canada

References

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.20 Study Investigators. Regional Nodal Irradiation in Early-Stage Breast Cancer. N Engl J Med. 2015 Jul 23;373(4):307-16. doi: 10.1056/NEJMoa1415340.

Reference Type: RESULT

PMID: 26200977 (View on PubMed)

Gross JP, Whelan TJ, Parulekar WR, Chen BE, Rademaker AW, Helenowski IB, Donnelly ED, Strauss JB. Development and Validation of a Nomogram to Predict Lymphedema After Axillary Surgery and Radiation Therapy in Women With Breast Cancer From the NCIC CTG MA.20 Randomized Trial. Int J Radiat Oncol Biol Phys. 2019 Sep 1;105(1):165-173. doi: 10.1016/j.ijrobp.2019.05.002. Epub 2019 May 11.

Reference Type: DERIVED

PMID: 31085285 (View on PubMed)

Other Identifiers

CAN-NCIC-MA20

Identifier Type: -

Identifier Source: secondary_id

NSABP-CAN-NCIC-MA20

Identifier Type: OTHER

Identifier Source: secondary_id

NCCTG-CAN-NCIC-MA20

Identifier Type: OTHER

Identifier Source: secondary_id

RTOG-CAN-NCIC-MA20

Identifier Type: OTHER

Identifier Source: secondary_id

SWOG-CAN-NCIC-MA20

Identifier Type: OTHER

Identifier Source: secondary_id

TROG-CAN-NCIC-MA20

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000067938

Identifier Type: OTHER

Identifier Source: secondary_id

MA20

Identifier Type: -

Identifier Source: org_study_id