RAPID: Randomized Trial of Accelerated Partial Breast Irradiation

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00282035
• Other study ID #: OCOG-2005-RAPID
• Secondary ID: CIHR Grant Numbe
• Status: Completed
• Phase: N/A
• Start date: January 2006
• Est. completion date: March 31, 2018

Study information

• Verified date: July 2018
• Source: Ontario Clinical Oncology Group (OCOG)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2135
• Est. completion date: March 31, 2018
• Est. primary completion date: March 31, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Radiation:
• APBI utilizing 3D-CRT radiation
Accelerated partial breast irradiation utilizing 3D-CRT
• Whole breast irradiation
Whole breast irradiation

Locations

Country	Name	City	State
Australia	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
Canada	BC Cancer Agency - Abbotsford Centre	Abbotsford	British Columbia
Canada	Brantford General Hospital	Brantford	Ontario
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	CHUS - Hopital Fleurimont	Fleurimont	Quebec
Canada	QE II HSC - Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	British Columbia Cancer Agency - Centre for the Southern Interior	Kelowna	British Columbia
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	CHUM - Hospital Notre Dame	Montreal	Quebec
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	McGill University - Jewish General Hospital	Montreal	Quebec
Canada	McGill University - Montreal General Hospital	Montreal	Quebec
Canada	Durham Regional Cancer Centre - Lakeridge Health Corporation	Oshawa	Ontario
Canada	Irving Greenberg Family Cancer Centre	Ottawa	Ontario
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	CHUQ, L'Hotel Dieu de Quebec	Quebec City	Quebec
Canada	Atlantic Health Sciences Corporation	Saint John	New Brunswick
Canada	Niagara Health System	St. Catharines	Ontario
Canada	Northeastern Regional Cancer Centre	Sudbury	Ontario
Canada	British Columbia Cancer Agency - Fraser Valley Centre	Surrey	British Columbia
Canada	Princess Margaret Hospital - University Health Network	Toronto	Ontario
Canada	British Columbia Cancer Agency - Vancouver Centre	Vancouver	British Columbia
Canada	British Columbia Cancer Agency - Vancouver Island Centre	Vancouver	British Columbia
Canada	Windsor Regional Cancer centre	Windsor	Ontario
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
New Zealand	Auckland City Hospital	Auckland	Auckland Region

Sponsors (3)

Lead Sponsor	Collaborator
Ontario Clinical Oncology Group (OCOG)	Canadian Breast Cancer Research Alliance, Canadian Institutes of Health Research (CIHR)

Countries where clinical trial is conducted

Australia,  Canada,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ipsilateral breast tumour recurrence defined as recurrent invasive or in situ cancer in the ipsilateral breast including the axillary tail.	ipsilateral breast tumour recurrence	ongoing throughout study
Secondary	adverse cosmetic outcome	adverse cosmetic outcome	evaluated at 1, 3, 5, 7 and 10 years
Secondary	disease free survival	disease free survival	ongoing throughout study
Secondary	event free survival	event free survival	ongoing throughout study
Secondary	overall survival	overall survival	ongoing throughout study
Secondary	radiation toxicity	radiation toxicity	ongoing throughout study
Secondary	quality of life based on questionnaire responses	quality of life	ongoing throughout study
Secondary	cost effectiveness	cost effectiveness	end of study