Trial of Radiation Fractionation Schedules for Once-a-Day Accelerated Partial Breast Irradiation (OPAR)

A Phase II Randomized Trial of Radiation Fractionation Schedules for Once-a-Day Accelerated Partial Breast Irradiation (OPAR)

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).

Study Overview

• Status: Completed
• Conditions: Breast Cancer; DCIS
• Intervention / Treatment: Radiation: APBI: 30 Gy; Radiation: APBI: 27.5 Gy

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.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Simcoe Muskoka Regional Cancer Centre, Royal Victoria Hospital
    • Hamilton, Ontario, Canada, L8V5C2
      • Juravinski Cancer Centre
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Regional Cancer Centre
    • London, Ontario, Canada, N6A4L6
      • London Regional Cancer Program; London Health Sciences Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre, Sunnybrook Health Sciences Centre
    • Windsor, Ontario, Canada, N8W 2X3
      • Windsor Regional Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuve-Rosemont
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM Centre Hospitalier de l'Université de Montréal
    • Quebec City, Quebec, Canada, G1R 2J6
      • CHUQ Pavillon Hotel-Dieu Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • CHUS - Hôpital Fleurimont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APBI: 30 Gy; Radiotherapy of 3 Dimensional Conformal Radiation Therapy (3DCRT) Accelerated Partial Breast Irradiation (APBI) 30 Gy in 5 daily fractions of 6 Gy	Radiation: APBI: 30 Gy; 30 Gy in 5 fractions of 6 Gy, delivered daily, Monday to Friday, over a period of 5-8 days. A multiple small field 3D-conformal or intensity modulated radiation therapy (IMRT) technique will be used.
Experimental: APBI: 27.5 Gy; Radiotherapy of 3 Dimensional Conformal Radiation Therapy (3DCRT) Accelerated Partial Breast Irradiation (APBI) 27.5 Gy in 5 daily fractions of 5.5 Gy	Radiation: APBI: 27.5 Gy; 27.5 Gy in 5 fractions of 5.5 Gy, delivered daily, Monday to Friday, over a period of 5-8 days. A multiple small field 3D-conformal or intensity modulated radiation therapy (IMRT) technique will be used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse cosmetic outcome using the EORTC Breast Cosmetic Rating System	The primary outcome is adverse cosmesis assessed at 2 years post randomization as determined by photographic assessment. The cosmetic outcome will be assessed by a panel of 3 trained radiation oncologists who are unaware of treatment allocation, using the EORTC Breast Cosmetic Rating System for cosmetic results for breast conserving treatment. The treated breast is compared with the untreated breast for size, shape, location of the areola/nipple, appearance of the surgical scar, presence of telangiectasia, and a global cosmetic score based on these factors. Characteristics are graded on a 4-point scale: 0 = excellent; 1 = good; 2 = fair; 3 = poor. A global cosmetic score of fair or poor will be used as the primary outcome of adverse cosmesis.	2 years post randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cosmetic deterioration (defined as any adverse change in the global cosmetic score)	defined as any adverse change in the global cosmetic score from baseline to 2 years. Subjects with global cosmetic scores that were stable or improved from baseline to 2 years will be scored as 'no deterioration'.	Baseline to two years
Radiation toxicity assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.02	defined as breast induration/fibrosis, shrinkage, and telangiectasia, which will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.02.	12, 24, 36 and 60 months
Ipsilateral breast tumour recurrence (IBTR)	defined as recurrent invasive or in situ cancer in the ipsilateral breast including the axillary tail. Histological evidence of local recurrence will be required.	Ongoing throughout study up to 5 years
Disease free survival (DFS)	defined as the time from randomization to the time of documented recurrent disease in the ipsilateral breast or regional nodes (supraclavicular, axillary or internal mammary) or distant sites (e.g. bone, liver, lung or brain).	Ongoing throughout study up to 5 years
Overall survival (OS)	defined as the time from randomization to death from any cause.	From date of randomization until the date of death up to 5 years

Collaborators and Investigators

• Sponsor: Ontario Clinical Oncology Group (OCOG)
• Collaborators: Canadian Breast Cancer Foundation
• Investigators: Principal Investigator: Do-Hoon Kim, MD, Juravinski Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: December 16, 2015
• First Submitted That Met QC Criteria: December 17, 2015
• First Posted (Estimated): December 22, 2015

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Breast Cancer; Radiotherapy; DCIS; Partial breast irradiation; Radiation fractions
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: OCOG-2015-OPAR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO