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Partial Breast Re-irradiation Using Ultra Hypofractionation (PRESERVE)

Sponsor
University Health Network, Toronto (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05592938
Collaborator
Sunnybrook Health Sciences Centre (Other), Royal Victoria Regional Health Centre (Other), AC Camargo Cancer Center (Other), King Hussein Cancer Center (Other), Tata Memorial Hospital (Other)
15
Enrollment
1
Arm
60
Anticipated Duration (Months)

Study Details

Study Description

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 they can accrue sufficient patient with rPBI who will be treated using 26 Gray(Gy) in 5 daily fractions over 1-week. Planned interim analysis after the 15 recruited patients for early toxicity evaluation with stopping rule for unacceptable toxicity.

Condition or Disease Intervention/Treatment Phase
  • Radiation: rPBI
 N/A

Detailed Description

Breast cancer is the leading cause of cancer in women worldwide, with over 2 million cases diagnosed every year. Although advances in treatment have led to an overall reduction in breast cancer mortality, survivors continue to have an ongoing risk of disease recurrence. For women who experience breast recurrence, mastectomy has historically been the only treatment approach offered. However, it has been associated with negative health outcomes, including reduced quality of life, depression and anxiety, and impaired sexual functioning. Fear of mastectomy has also been associated with delays in seeking appropriate and timely management of disease. As a result, there is increasing interest to identify treatment options that include breast preservation.

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. However, previously published studies have used long fractionation regimens for rPBI delivered over 3 to 5 weeks, which can present a challenge for both patients and health systems. This is particularly true in low- and middle-income countries, where more than half of new breast cancer cases now occur.

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 they can accrue sufficient patient with rPBI who will be treated using 26Gy in 5 daily fractions over 1-week. Planned interim analysis after the 15 recruited patients for early toxicity evaluation with stopping rule for unacceptable toxicity.

Using an international network of comprehensive cancer centers, this study will advance global knowledge of how to optimally treat woman with this disease.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
15 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Partial Breast Re-irradiation Using Ultra Hypofractionation: Phase 2 Multi-institutional Study (PRESERVE)
Anticipated Study Start Date :
Dec 1, 2022
Anticipated Primary Completion Date :
Dec 1, 2027
Anticipated Study Completion Date :
Dec 1, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: rPBI

26Gy in 5 daily fractions over 1-week

Radiation: rPBI
External beam partial breast reirradiation (rPBI) using 26Gy in 5 fractions delivered daily over 1-week

Outcome Measures

Primary Outcome Measures

  1. Number of participants accrued to the trial [During accrual period, up to 2 years]

    The primary endpoint will be determined by the ability to complete accrual of 15 patients to the study in 2 years.

Secondary Outcome Measures

  1. Frequency radiation-associated toxicity (acute) [3 months, 1 year, 3 years, and 5 years post rPBI]

    Radiation-associated toxicities (acute) will be graded according to CTCAE v5.0 by physicians. Toxicity associated with treatment will be summarized using frequency with 95% Clopper-Pearson confidence intervals by grade at each scheduled follow up.

  2. Percentage radiation-associated toxicity (acute) [3 months, 1 year, 3 years, and 5 years post rPBI]

    Radiation-associated toxicities (acute) will be graded according to CTCAE v5.0 by physicians. Toxicity associated with treatment will be summarized using percentage with 95% Clopper-Pearson confidence intervals by grade at each scheduled follow up.

  3. Frequency radiation-associated toxicity (late) [3 months, 1 year, 3 years, and 5 years post rPBI]

    Radiation-associated toxicities (late) will be graded according to CTCAE v5.0 by physicians. Toxicity associated with treatment will be summarized using frequency with 95% Clopper-Pearson confidence intervals by grade at each scheduled follow up.

  4. Percentage radiation-associated toxicity (late) [3 months, 1 year, 3 years, and 5 years post rPBI]

    Radiation-associated toxicities (late) will be graded according to CTCAE v5.0 by physicians. Toxicity associated with treatment will be summarized using percentage with 95% Clopper-Pearson confidence intervals by grade at each scheduled follow up.

  5. Risk of local recurrence (invasive and DCIS) [3 months, 1 year, 3 years, and 5 years post rPBI]

    Cumulative incidence function will be used to estimate local recurrence with death as a competing risk.

  6. Risk of distant recurrence (invasive and DCIS) [3 months, 1 year, 3 years, and 5 years post rPBI]

    Cumulative incidence function will be used to estimate distant recurrence and distance recurrence with death as a competing risk.

  7. Location of local recurrence (in-field) (frequency) [3 months, 1 year, 3 years, and 5 years post rPBI]

    Location of recurrence will be summarized by frequency.

  8. Location of local recurrence (in-field) (percentage) [3 months, 1 year, 3 years, and 5 years post rPBI]

    Location of recurrence will be summarized by percentage.

  9. Location of local recurrence (out-of-field) (frequency) [3 months, 1 year, 3 years, and 5 years post rPBI]

    Location of recurrence will be summarized by frequency.

  10. Location of local recurrence (out-of-field) (percentage) [3 months, 1 year, 3 years, and 5 years post rPBI]

    Location of recurrence will be summarized by percentage

  11. Risk of local recurrence after rPBI requiring mastectomy [3 months, 1 year, 3 years, and 5 years post rPBI]

    Cumulative incidence function will be used to estimate local recurrence after rPBI requiring mastectomy with death as a competing risk

  12. Invasive breast cancer free survival [3 months, 1 year, 3 years, and 5 years post rPBI]

    Kaplan-Meier method will be used to estimate invasive breast cancer free survival

  13. Overall survival [3 months, 1 year, 3 years, and 5 years post rPBI]

    Kaplan-Meier method will be used to estimate overall survival

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 99 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Age > 18 years

  • In-breast recurrence confirmed as unicentric

  • Tumour <3.0 cm in greatest diameter on pathologic examination, including both invasive and non-invasive components

  • 1 year after completion of prior adjuvant whole or partial breast radiotherapy

  • Clinically node negative

  • Negative margins (no tumour on ink)

  • Recovered from surgery with the incision completely healed and no signs of infection

  • Negative metastatic work-up (no evidence of distant metastases on bone scan, and computerized tomography (CT) scans of the thorax, abdomen, and pelvis; or using (FDG) Positron emission tomography (PET)-CT).

Exclusion Criteria:

  • Infiltrating Lobular Carcinoma

  • Multifocal or multicentric disease

  • 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 (Level I 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • University Health Network, Toronto
  • Sunnybrook Health Sciences Centre
  • Royal Victoria Regional Health Centre
  • AC Camargo Cancer Center
  • King Hussein Cancer Center
  • Tata Memorial Hospital

Investigators

  • Principal Investigator: Danielle Rodin, MD, Princess Margaret Cancer Centre
  • Principal Investigator: Anne Koch, MD, Princess Margaret Cancer Centre
  • Principal Investigator: Fadwa Abdel-Rahman, MBBS, Princess Margaret Cancer Centre

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT05592938
Other Study ID Numbers:
  • 22-5074
First Posted:
Oct 25, 2022
Last Update Posted:
Oct 25, 2022
Last Verified:
Oct 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by University Health Network, Toronto
Hypofractionated
Additional relevant MeSH terms:
Breast Neoplasms

Study Results

No Results Posted as of Oct 25, 2022