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

Breast Cancer Clinical Trial

— OPAR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02637024
• Other study ID #: OCOG-2015-OPAR
• Status: Completed
• Phase: Phase 2
• Start date: May 2016
• Est. completion date: December 2022

Study information

• Verified date: August 2023
• Source: Ontario Clinical Oncology Group (OCOG)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 280
• Est. completion date: December 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• DCIS

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Simcoe Muskoka Regional Cancer Centre, Royal Victoria Hospital	Barrie	Ontario
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	Grand River Regional Cancer Centre	Kitchener	Ontario
Canada	London Regional Cancer Program; London Health Sciences Centre	London	Ontario
Canada	CHUM Centre Hospitalier de L'Université de Montréal	Montreal	Quebec
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	CHUQ Pavillon Hotel-Dieu Quebec	Quebec City	Quebec
Canada	CHUS - Hopital Fleurimont	Sherbrooke	Quebec
Canada	Odette Cancer Centre, Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Windsor Regional Cancer Centre	Windsor	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Ontario Clinical Oncology Group (OCOG)	Canadian Breast Cancer Foundation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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