RAPID: Randomized Trial of Accelerated Partial Breast Irradiation

NCT ID: NCT00282035

Last Updated: 2018-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 2135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2018-03-31

Brief Summary

To determine if Accelerated Partial Breast Irradiation, using 3D CRT, is as effective as Whole Breast Irradiation following breast conserving surgery in women with an new histological diagnosis of ductal carcinoma in situ only or invasive breast cancer without evidence of metastatic disease. Effectiveness will be determined by the rate of ipsilateral breast tumour recurrence.

General objective is to improve the convenience and quality of life of female patients who receive breast irradiation.

Detailed Description

Following breast conserving surgery or on completion of chemotherapy, patients will be stratified according to age, tumour histology, tumour size, adjuvant hormonal therapy and clinical centre. Patients will be allocated to receive either whole breast irradiation or 3D CRT accelerated partial breast irradiation.

Radiation therapy will be administered as soon as possible following the healing of the surgical incision (3-4 weeks) and within 12 weeks if the patient is not treated with chemotherapy. If the patient is treated with chemotherapy, radiation therapy will begin after 2 weeks and not beyond 8 weeks after the last dose of chemotherapy.

Patients treated with whole breast irradiation will receive a total dose of 42.5 Gy in 16 fractions, given on a daily basis, over a time period of 22 days. Patients with large breast size are permitted to receive a total dose of 50 Gy in 25 fractions, given on a daily basis, over a time period of 35 days. Boost irradiation is permitted in patients treated with whole breast irradiation. Boost irradiation of 10 Gy/4-5 fractions daily over a time period of 4-7 days is permitted for patients deemed at moderate to high risk of local recurrence as per local cancer centre guidelines.

Patients treated with 3D CRT accelerated partial breast irradiation will receive a total dose of 38.5 Gy in 10 fractions, delivered twice a day, over a time period of 5-8 days. Each daily dose must be separated by 6-8 hours.

Patients will be followed indefinitely and assessed formally at 6 and 12 months after the date of randomization and then on a yearly basis. Patients will be assessed for acute and late radiation toxicity, cardiac toxicity, recurrent disease, new primary cancer, cosmetic outcome, quality of life and overall survival.

Conditions

Breast Cancer

Study Design

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

Study Groups

APBI utilizing 3D-CRT radiation

Accelerated partial breast irradiation utilizing 3D-CRT

Group Type: EXPERIMENTAL

APBI utilizing 3D-CRT radiation

Intervention Type: RADIATION

Accelerated partial breast irradiation utilizing 3D-CRT

Whole breast irradiation

Whole breast irradiation

Group Type: OTHER

Whole breast irradiation

Intervention Type: RADIATION

Whole breast irradiation

Interventions

APBI utilizing 3D-CRT radiation

Accelerated partial breast irradiation utilizing 3D-CRT

Intervention Type: RADIATION

Whole breast irradiation

Whole breast irradiation

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 1a. Female patient with a new histological diagnosis of DCIS only. OR

1b. Female patient with a new histological diagnosis of invasive carcinoma of the breast and no evidence of metastatic disease.

2. Treated by BCS with microscopically clear resection margins for invasive and non-invasive disease (or no residual disease on re- excision).

3. Negative axillary node involvement including micrometastasis <= 0.2mm or positive cells only identified by IHC as determined either by: (i) sentinel node biopsy (ii) axillary node dissection or (iii) clinical exam for patients with DCIS only

Exclusion Criteria

• 1. Age < 40 years.

2. A known deleterious mutation in BRCA 1 and/or BRCA 2.

3. Tumour size > 3 cm in greatest diameter on pathological examination (including both the invasive and non-invasive component).

4. Tumour histology limited to lobular carcinoma only.

5. History of cancer:

• Patients with another active malignancy or malignancy treated < 5 years prior to randomization are excluded.
• Patients with a prior diagnosis of invasive or non-invasive breast cancer in either breast are excluded regardless of disease free interval. Patients with concurrent invasive or non-invasive contralateral breast cancer are also excluded.
• Patients with prior or concurrent basal cell or squamous cell skin cancers are eligible for the trial.

6. More than one primary tumour in different quadrants of the same breast.

7. Previous irradiation to the ipsilateral breast that would preclude whole breast irradiation.

8. Presence of an ipsilateral breast implant or pacemaker.

9. Serious non-malignant disease (e.g. cardiovascular, pulmonary, systemic lupus erythematosus (SLE), scleroderma) which would preclude definitive radiation treatment.

10. Estrogen receptor status (ER) not known.

11. For patients not treated with adjuvant chemotherapy: unable to commence radiation therapy within 12 weeks of the last surgical procedure on the breast.

12. For patients treated with adjuvant chemotherapy: unable to commence within 8 weeks of the last dose of chemotherapy.

13. Currently pregnant or lactating.

14. Psychiatric or addictive disorders which would preclude obtaining informed consent or adherence to protocol.

15. Geographic inaccessibility for follow-up.

16. Inability to localize surgical cavity on CT (i.e., no evidence of surgical clips or seroma).

17. Inability to adequately plan the patient for the experimental technique.

• Minimum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Canadian Breast Cancer Research Alliance

OTHER

Sponsor Role: collaborator

Ontario Clinical Oncology Group (OCOG)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tim Whelan, MD

Role: PRINCIPAL_INVESTIGATOR

Ontario Clinical Oncology Group / Juravinski Cancer Centre

Ivo Olivotto, MD

Role: PRINCIPAL_INVESTIGATOR

British Columbia Cancer Agency - Vancouver Island Centre

Mark Levine, MD

Role: STUDY_DIRECTOR

Ontario Clinical Oncology Group (OCOG)

Locations

Peter MacCallum Cancer Centre

Bendigo, Victoria, Australia

Peter MacCallum Cancer Centre

Box Hill, Victoria, Australia

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

Peter MacCallum Cancer Centre - Monash Medical Centre Moorabbin

Melbourne, Victoria, Australia

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

BC Cancer Agency - Abbotsford Centre

Abbotsford, British Columbia, Canada

British Columbia Cancer Agency - Centre for the Southern Interior

Kelowna, British Columbia, Canada

British Columbia Cancer Agency - Fraser Valley Centre

Surrey, British Columbia, Canada

British Columbia Cancer Agency - Vancouver Centre

Vancouver, British Columbia, Canada

British Columbia Cancer Agency - Vancouver Island Centre

Vancouver, British Columbia, Canada

Cancer Care Manitoba

Winnipeg, Manitoba, Canada

Atlantic Health Sciences Corporation

Saint John, New Brunswick, Canada

QE II HSC - Nova Scotia Cancer Centre

Halifax, Nova Scotia, Canada

Brantford General Hospital

Brantford, Ontario, Canada

Northeastern Regional Cancer Centre

Greater Sudbury, Ontario, Canada

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Grand River Regional Cancer Centre

Kitchener, Ontario, Canada

London Regional Cancer Centre

London, Ontario, Canada

Credit Valley Hospital - Carlo Fidani Peel Regional Cancer Center

Mississauga, Ontario, Canada

Durham Regional Cancer Centre - Lakeridge Health Corporation

Oshawa, Ontario, Canada

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Irving Greenberg Family Cancer Centre

Ottawa, Ontario, Canada

Niagara Health System

St. Catharines, Ontario, Canada

Princess Margaret Hospital - University Health Network

Toronto, Ontario, Canada

Windsor Regional Cancer centre

Windsor, Ontario, Canada

CHUS - Hopital Fleurimont

Fleurimont, Quebec, Canada

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

CHUM - Hospital Notre Dame

Montreal, Quebec, Canada

McGill University - Montreal General Hospital

Montreal, Quebec, Canada

McGill University - Jewish General Hospital

Montreal, Quebec, Canada

CHUQ, L'Hotel Dieu de Quebec

Québec, Quebec, Canada

Auckland City Hospital

Auckland, Auckland, New Zealand

Countries

Australia; Canada; New Zealand

References

Whelan TJ, Julian JA, Berrang TS, Kim DH, Germain I, Nichol AM, Akra M, Lavertu S, Germain F, Fyles A, Trotter T, Perera FE, Balkwill S, Chafe S, McGowan T, Muanza T, Beckham WA, Chua BH, Gu CS, Levine MN, Olivotto IA; RAPID Trial Investigators. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial. Lancet. 2019 Dec 14;394(10215):2165-2172. doi: 10.1016/S0140-6736(19)32515-2. Epub 2019 Dec 5.

Reference Type: DERIVED

PMID: 31813635 (View on PubMed)

Other Identifiers

CIHR Grant Number: MCT-78567

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

OCOG-2005-RAPID

Identifier Type: -

Identifier Source: org_study_id