Clinical trial NCT05592938: Partial Breast Re-irradiation Using Ultra Hypofractionation (PRESERVE)
Official title: Partial Breast Re-irradiation Using Ultra Hypofractionation: Phase 2 Multi-institutional Study (PRESERVE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Breast Cancer Recurrent
Keywords: Hypofractionated
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Sunnybrook Health Sciences Centre
name: Royal Victoria Regional Health Centre
name: AC Camargo Cancer Center
name: King Hussein Cancer Center
name: Tata Memorial Hospital
name: NYU Langone Health
name: Centre hospitalier de l'Université de Montréal (CHUM)
name: Peter MacCallum Cancer Centre, Australia
name: CHU de Quebec (Université Laval)
name: l'Hopital Maisonneuve-Rosemont
name: L'Institut de recherche du Centre universitaire de sante McGill
First posted: 2022-10-25
Enrollment: 171
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Breast-conserving surgery followed by re-irradiation with partial breast irradiation (rPBI) has recently been found to be a safe alternative to mastectomy for women who have undergone prior whole breast radiation. By reducing the volume of tissue receiving radiation, rPBI has been associated with less toxicity and improved cosmetic outcomes. For many women with early-stage breast cancer, shorter 1-week (5-fraction) courses of breast radiation (ultra-fractionation) have been found to be equivalent to longer fractionation schedules in the upfront treatment setting. These 1-week schedules are more convenient for patients, with fewer treatments and shorter overall treatment time. The investigators hypothesize that a 1-week ultra-hypofractionated rPBI regimen following breast-conserving surgery (BCS) for local recurrence or new primary breast cancer in the previously irradiated breast (LR) will be associated with acceptable toxicity at 1 year (\<13% grade \>3 toxicity).

Detailed description: Most women affected by breast cancer are treated with breast-conserving surgery to remove the tumour, followed by radiation to reduce the risk of recurrence. Unfortunately, some women will experience recurrence of the cancer in the previously treated breast. These recurrences have historically been treated by removing the whole breast or a second breast-conserving surgery followed by 3 to 5 weeks of radiation. These treatments can negatively impact mental health and quality of life or lead to harmful side effects that could impact the skin, breast, ribs, heart and lungs.

Breast-conserving surgery followed by re-irradiation with partial breast irradiation (rPBI) has recently been found to be a safe alternative to mastectomy for women who have undergone prior whole breast radiation. By reducing the volume of tissue receiving radiation, rPBI has been associated with less toxicity and improved cosmetic outcomes. For many women with early-stage breast cancer, shorter 1-week (5-fraction) courses of breast radiation (ultra-fractionation) have been found to be equivalent to longer fractionation schedules in the upfront treatment setting. These 1-week schedules are more convenient for patients, with fewer treatments and shorter overall treatment time. The investigators hypothesize that a 1-week ultra-hypofractionated rPBI regimen following breast-conserving surgery (BCS) for local recurrence or new primary breast cancer in the previously irradiated breast (LR) will be associated with acceptable toxicity at 1 year (\<13% grade \>3 toxicity).

The target population for this study is women with localized recurrent or new primary breast cancer in the previously irradiated breast. This is a prospective single arm phase 2 trial of external beam rPBI using 26Gy in 5 fractions delivered daily over 1-week after a second lumpectomy for LR following prior BCS and adjuvant whole or partial breast irradiation. Using a multi-institutional and international network of comprehensive cancer centers, this study will advance global knowledge of how to optimally treat women with this disease.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years
* In-breast recurrence or new primary (ductal carcinoma in situ (DCIS) or invasive carcinoma)
* Tumour \<3.0 cm in greatest diameter on pathologic examination, including both invasive and non-invasive components
* \>5 years after completion of prior adjuvant whole or partial breast radiotherapy (prior nodal radiotherapy permitted)
* Clinically node negative
* Negative margins (no tumour on ink)
* Recovered from surgery with the incision completely healed and no signs of infection

Exclusion Criteria:

* Multicentric disease (patients with multifocal breast cancer in the same quadrant are eligible)
* Tumour histology limited to lobular carcinoma only
* Extensive intraductal component
* T4 disease
* Node positive or distant metastatic disease
* Serious non-malignant disease (cardiovascular, pulmonary, systemic lupus erythematosus, scleroderma), which would preclude radiation treatment
* Currently pregnant or lactating
* Presence of an ipsilateral breast implant or pacemaker
* Unable to commence radiation within 16 weeks of breast-conserving surgery (or last surgical procedure on the breast) or within 12 weeks from last cycle of adjuvant chemotherapy
* Unable to clearly define the surgical cavity (oncoplastic procedures are permitted provided the tumor bed is well delineated with surgical clips).
* Psychiatric disorders which would preclude obtaining informed consent or adherence to protocol
* Grade II or more late skin toxicity from prior radiation evaluated and graded using CTCAE v5.0

Primary outcomes:
measure: Grade ≥3 toxicity associated with treatment
timeFrame: During accrual period, up to 3 years
Secondary outcomes:
measure: Frequency radiation-associated toxicity (acute)
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Percentage radiation-associated toxicity (acute)
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Frequency radiation-associated toxicity (late)
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Percentage radiation-associated toxicity (late)
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Risk of local recurrence (invasive and DCIS)
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Risk of distant recurrence (invasive and DCIS)
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Location of local recurrence (in-field) (frequency)
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Location of local recurrence (in-field) (percentage)
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Location of local recurrence (out-of-field) (frequency)
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Location of local recurrence (out-of-field) (percentage)
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Risk of local recurrence after rPBI requiring mastectomy
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Invasive breast cancer free survival
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Overall survival
timeFrame: 3 months, 1 year, 2 year, 3 years, 4 years and 5 years post rPBI
measure: Satisfaction with breasts
timeFrame: Baseline, 1 year, 3 years, and 5 years post rPBI
measure: Financial toxicity associated with treatment
timeFrame: Baseline, 3 months, 1 year, and 3 years post rPBI
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: São Paulo
country: Brazil
facility: A.C.Camargo Cancer Center
state: SP
city: London
country: Canada
facility: Verspeeten Family Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: CHU de Québec-Université Laval
state: Quebec
city: Montreal
country: Canada
facility: Hôpital Maisonneuve-Rosemont - CIUSSS de l'Est-de-l'Île-de-Montréal
state: Quebec
city: Montreal
country: Canada
facility: Centre hospitalier de l'Université de Montréal
state: Quebec
city: Amman
country: Jordan
facility: King Hussein Cancer Centre
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Danielle Rodin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Margaret Cancer Centre
name: Anne Koch, MD
role: PRINCIPAL_INVESTIGATOR
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