Clinical trial NCT00282035: RAPID: Randomized Trial of Accelerated Partial Breast Irradiation
Official title: An RCT to Determine if APBI, Utilizing 3D CRT, is as Effective as Whole Breast Irradiation Following Breast Conserving Surgery in Women With Ductal Carcinoma in Situ or Invasive Breast Cancer With Negative Axillary Lymph Nodes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: breast cancer
breast tumour
DCIS
female
breast conserving surgery
irradiation
whole breast irradiation
3D CRT accelerated partial breast irradiation
cosmetic outcome
quality of life
Lead sponsor: Ontario Clinical Oncology Group (OCOG)
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Canadian Breast Cancer Research Alliance
First posted: 2006-01-25
Enrollment: 2135
Sex: FEMALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: ipsilateral breast tumour recurrence defined as recurrent invasive or in situ cancer in the ipsilateral breast including the axillary tail.
timeFrame: ongoing throughout study
Secondary outcomes:
measure: adverse cosmetic outcome
timeFrame: evaluated at 1, 3, 5, 7 and 10 years
measure: disease free survival
timeFrame: ongoing throughout study
measure: event free survival
timeFrame: ongoing throughout study
measure: overall survival
timeFrame: ongoing throughout study
measure: radiation toxicity
timeFrame: ongoing throughout study
measure: quality of life based on questionnaire responses
timeFrame: ongoing throughout study
measure: cost effectiveness
timeFrame: end of study
Other outcomes:
Locations:
city: Bendigo
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Box Hill
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre - Monash Medical Centre Moorabbin
state: Victoria
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Abbotsford
country: Canada
facility: BC Cancer Agency - Abbotsford Centre
state: British Columbia
city: Kelowna
country: Canada
facility: British Columbia Cancer Agency - Centre for the Southern Interior
state: British Columbia
city: Surrey
country: Canada
facility: British Columbia Cancer Agency - Fraser Valley Centre
state: British Columbia
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Centre
state: British Columbia
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Island Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: Saint John
country: Canada
facility: Atlantic Health Sciences Corporation
state: New Brunswick
city: Halifax
country: Canada
facility: QE II HSC - Nova Scotia Cancer Centre
state: Nova Scotia
city: Brantford
country: Canada
facility: Brantford General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Kitchener
country: Canada
facility: Grand River Regional Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Centre
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley Hospital - Carlo Fidani Peel Regional Cancer Center
state: Ontario
city: Oshawa
country: Canada
facility: Durham Regional Cancer Centre - Lakeridge Health Corporation
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Irving Greenberg Family Cancer Centre
state: Ontario
city: St. Catharines
country: Canada
facility: Niagara Health System
state: Ontario
city: Sudbury
country: Canada
facility: Northeastern Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital - University Health Network
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Cancer centre
state: Ontario
city: Fleurimont
country: Canada
facility: CHUS - Hopital Fleurimont
state: Quebec
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Hospital Notre Dame
state: Quebec
city: Montreal
country: Canada
facility: McGill University - Montreal General Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University - Jewish General Hospital
state: Quebec
city: Quebec City
country: Canada
facility: CHUQ, L'Hotel Dieu de Quebec
state: Quebec
city: Auckland
country: New Zealand
facility: Auckland City Hospital
state: Auckland Region
Study officials:
affiliation: Ontario Clinical Oncology Group / Juravinski Cancer Centre
name: Tim Whelan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: British Columbia Cancer Agency - Vancouver Island Centre
name: Ivo Olivotto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ontario Clinical Oncology Group (OCOG)
name: Mark Levine, MD
role: STUDY_DIRECTOR
References:
citation: 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.