Clinical trial NCT02637024: Trial of Radiation Fractionation Schedules for Once-a-Day Accelerated Partial Breast Irradiation
Official title: A Phase II Randomized Trial of Radiation Fractionation Schedules for Once-a-Day Accelerated Partial Breast Irradiation (OPAR)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
DCIS
Keywords: Breast Cancer
DCIS
Radiotherapy
Partial breast irradiation
Radiation fractions
Lead sponsor: Ontario Clinical Oncology Group (OCOG)
Sponsor class: OTHER
Collaborators: name: Canadian Breast Cancer Foundation
First posted: 2015-12-22
Enrollment: 280
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-centre randomized phase II trial in women with invasive carcinoma of the breast with negative axillary nodes or Ductal Carcinoma In-situ (DCIS) treated by Breast Conserving Surgery (BCS). Eligible, consenting patients will be randomly allocated to receive radiotherapy of 3 Dimensional Conformal Radiation Therapy (3DCRT) Accelerated Partial Breast Irradiation (APBI) 30 Gray (Gy) in 5 daily fractions of 6Gy or 27.5Gy in 5 daily fractions of 5.5Gy over one week. Patients will be followed at 12, 24, 36 and 60 months post randomization. Cosmetic outcome will be measured using photographs and evaluated by a panel of trained radiation oncologists. Radiation toxicity will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).

Detailed description: Women with invasive carcinoma of the breast with negative axillary nodes or DCIS, following BCS and/or chemotherapy, who meet the inclusion criteria will be screened and approached for eligibility assessment and potential study enrollment. All potentially eligible and consenting patients who do not meet the exclusion criteria will have a Computed Tomography (CT) simulation of the ipsilateral breast prior to randomization. All cases will be required to be planned prior to the randomization to ensure that dosimetric coverage and normal tissue restrictions can be met. If the seroma is not clearly visible or if the surgical clips do not adequately identify a previous surgical cavity, the patient will not be eligible for randomization.

Eligible, consenting patients will be randomly allocated to receive radiotherapy of 3DCRT APBI 30Gy in 5 daily fractions of 6Gy or 27.5Gy in 5 daily fractions of 5.5Gy over one week. Patients will be followed at 12, 24, 36 and 60 months post randomization. Cosmetic outcome will be measured using photographs and evaluated by a panel of trained radiation oncologists using the EORTC Breast Cosmetic Rating System. Radiation toxicity will be assessed using the NCI CTCAE version 4.02. The primary outcome is adverse cosmetic outcome at 2 years. The trial will be conducted in clinical centres within Canada.

Eligibility criteria: Inclusion Criteria:

1. Females with a new histological diagnosis of DCIS or invasive carcinoma of the breast with 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 positive cells only identified by Immunohistochemistry (IHC) as determined either by sentinel node biopsy or axillary node dissection, or a clinical exam for patients with DCIS only.

Exclusion Criteria:

1. Age less than 50 years
2. Known to be Breast Cancer Type 1 Susceptibility Protein (BRCA 1) and/or Breast Cancer Type 2 Susceptibility Protein (BRCA 2) positive
3. Tumour size \>3 cm in greatest diameter on pathological examination (including the invasive and non-invasive components)
4. Tumour invades the skin (i.e. T4 disease)
5. Tumour histology limited to lobular carcinoma only
6. Grade III invasive breast carcinoma or nuclear grade III for patients with DCIS alone
7. Triple negative invasive breast cancer
8. Her2+ve invasive breast cancer that will not receive Herceptin
9. Bilateral invasive malignancy of the breast (synchronous or metachronous)
10. More than one primary tumor in different quadrants of the same breast
11. Presence of an ipsilateral breast implant or pacemaker
12. Status for adjuvant systemic therapy not determined
13. Unable to commence radiation therapy:

    1. within 12 weeks of the last surgical procedure on the breast, or
    2. within 8 weeks of the last dose of chemotherapy
14. Previous or concurrent malignancies except:

    1. Non-melanoma skin cancer
    2. Carcinoma in-situ of the cervix
    3. Invasive carcinoma of the cervix, endometrium, colon and thyroid, treated 5 years prior to study entry with no evidence of disease
15. Serious non-malignant disease (e.g. cardiovascular, pulmonary, systemic lupus erythematosus (SLE), scleroderma) which would preclude definitive radiation treatment.
16. Current pregnancy or lactating.
17. Psychiatric or addictive disorders which would preclude obtaining informed consent or adherence to the protocol.
18. Geographic inaccessibility for follow-up.
19. Inability to localize surgical cavity on CT (i.e. no evidence of surgical clips or seroma)
20. Inability to adequately plan the patient for the experimental technique.

Primary outcomes:
measure: Adverse cosmetic outcome using the EORTC Breast Cosmetic Rating System
timeFrame: 2 years post randomization
Secondary outcomes:
measure: Cosmetic deterioration (defined as any adverse change in the global cosmetic score)
timeFrame: Baseline to two years
measure: Radiation toxicity assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.02
timeFrame: 12, 24, 36 and 60 months
measure: Ipsilateral breast tumour recurrence (IBTR)
timeFrame: Ongoing throughout study up to 5 years
measure: Disease free survival (DFS)
timeFrame: Ongoing throughout study up to 5 years
measure: Overall survival (OS)
timeFrame: From date of randomization until the date of death up to 5 years
Other outcomes:
Locations:
city: Barrie
country: Canada
facility: Simcoe Muskoka Regional Cancer Centre, Royal Victoria 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 Program; London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre, Sunnybrook Health Sciences Centre
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: CHUM Centre Hospitalier de L'Université de Montréal
state: Quebec
city: Quebec City
country: Canada
facility: CHUQ Pavillon Hotel-Dieu Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS - Hopital Fleurimont
state: Quebec
Study officials:
affiliation: Juravinski Cancer Centre
name: Do-Hoon Kim, MD
role: PRINCIPAL_INVESTIGATOR
References: