Partial Breast Re-irradiation Using Ultra Hypofractionation (PRESERVE)

Breast Cancer Clinical Trial

— PRESERVE  

Official title:

Partial Breast Re-irradiation Using Ultra Hypofractionation: Phase 2 Multi-institutional Study (PRESERVE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05592938
• Other study ID #: 22-5074
• Status: Recruiting
• Phase: N/A
• Start date: June 27, 2023
• Est. completion date: June 27, 2027

Study information

• Verified date: June 2023
• Source: University Health Network, Toronto
• Contact: Danielle Rodin, MD
• Phone: (416) 946-6513
• Email: danielle.rodin[@]rmp.uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: June 27, 2027
• Est. primary completion date: June 27, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Cancer Recurrent
• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (9)

Lead Sponsor	Collaborator
University Health Network, Toronto	AC Camargo Cancer Center, Centre hospitalier de l'Université de Montréal (CHUM), King Hussein Cancer Center, NYU Langone Health, Peter MacCallum Cancer Centre, Australia, Royal Victoria Regional Health Centre, Sunnybrook Health Sciences Centre, Tata Memorial Hospital

Country where clinical trial is conducted

Canada, 

References & Publications (12)

Abdel-Razeq H, Mansour A, Jaddan D. Breast Cancer Care in Jordan. JCO Glob Oncol. 2020 Feb;6:260-268. doi: 10.1200/JGO.19.00279. — View Citation

Arthur DW, Winter KA, Kuerer HM, Haffty B, Cuttino L, Todor DA, Anne PR, Anderson P, Woodward WA, McCormick B, Cheston S, Sahijdak WM, Canaday D, Brown DR, Currey A, Fisher CM, Jagsi R, Moughan J, White JR. Effectiveness of Breast-Conserving Surgery and 3-Dimensional Conformal Partial Breast Reirradiation for Recurrence of Breast Cancer in the Ipsilateral Breast: The NRG Oncology/RTOG 1014 Phase 2 Clinical Trial. JAMA Oncol. 2020 Jan 1;6(1):75-82. doi: 10.1001/jamaoncol.2019.4320. — View Citation

Barrios CH, Reinert T, Werutsky G. Global Breast Cancer Research: Moving Forward. Am Soc Clin Oncol Educ Book. 2018 May 23;38:441-450. doi: 10.1200/EDBK_209183. — View Citation

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum In: CA Cancer J Clin. 2020 Jul;70(4):313. — View Citation

Brunt AM, Haviland JS, Sydenham M, Agrawal RK, Algurafi H, Alhasso A, Barrett-Lee P, Bliss P, Bloomfield D, Bowen J, Donovan E, Goodman A, Harnett A, Hogg M, Kumar S, Passant H, Quigley M, Sherwin L, Stewart A, Syndikus I, Tremlett J, Tsang Y, Venables K, Wheatley D, Bliss JM, Yarnold JR. Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer. J Clin Oncol. 2020 Oct 1;38(28):3261-3272. doi: 10.1200/JCO.19.02750. Epub 2020 Jul 14. — View Citation

Fingeret MC, Nipomnick S, Guindani M, Baumann D, Hanasono M, Crosby M. Body image screening for cancer patients undergoing reconstructive surgery. Psychooncology. 2014 Aug;23(8):898-905. doi: 10.1002/pon.3491. Epub 2014 Feb 6. — View Citation

Khader J, Glicksman RM, Mheid S, Mansour A, Giuliani ME, Gospodarowicz M, Almousa A, Abdel-Razeq H, Rodin D. Enhancing International Cancer Organization Collaborations: King Hussein Cancer Center and Princess Margaret Cancer Centre Model for Collaboration. J Cancer Educ. 2022 Jun;37(3):763-769. doi: 10.1007/s13187-020-01878-z. Epub 2020 Sep 14. — View Citation

Korzets Y, Lee G, Espin-Garcia O, Purdie T, Koch AC, Hodgson D, Barry A, Fyles A. The Role of Partial Breast Radiation in the Previously Radiated Breast. Am J Clin Oncol. 2019 Dec;42(12):932-936. doi: 10.1097/COC.0000000000000584. — View Citation

Loibl S, Poortmans P, Morrow M, Denkert C, Curigliano G. Breast cancer. Lancet. 2021 May 8;397(10286):1750-1769. doi: 10.1016/S0140-6736(20)32381-3. Epub 2021 Apr 1. Erratum In: Lancet. 2021 May 8;397(10286):1710. — View Citation

Martei YM, Vanderpuye V, Jones BA. Fear of Mastectomy Associated with Delayed Breast Cancer Presentation Among Ghanaian Women. Oncologist. 2018 Dec;23(12):1446-1452. doi: 10.1634/theoncologist.2017-0409. Epub 2018 Jun 29. — View Citation

Murray Brunt A, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, Chan C, Churn M, Cleator S, Coles CE, Goodman A, Harnett A, Hopwood P, Kirby AM, Kirwan CC, Morris C, Nabi Z, Sawyer E, Somaiah N, Stones L, Syndikus I, Bliss JM, Yarnold JR; FAST-Forward Trial Management Group. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020 May 23;395(10237):1613-1626. doi: 10.1016/S0140-6736(20)30932-6. Epub 2020 Apr 28. — View Citation

Rodin D, Tawk B, Mohamad O, Grover S, Moraes FY, Yap ML, Zubizarreta E, Lievens Y. Hypofractionated radiotherapy in the real-world setting: An international ESTRO-GIRO survey. Radiother Oncol. 2021 Apr;157:32-39. doi: 10.1016/j.radonc.2021.01.003. Epub 2021 Jan 14. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants accrued to the trial	The primary endpoint will be determined by the ability to complete accrual of 15 patients to the study in 2 years.	During accrual period, up to 2 years
Secondary	Frequency radiation-associated toxicity (acute)	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.	3 months, 1 year, and 3 years post rPBI
Secondary	Percentage radiation-associated toxicity (acute)	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 months, 1 year, and 3 years post rPBI
Secondary	Frequency radiation-associated toxicity (late)	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.	3 months, 1 year, and 3 years post rPBI
Secondary	Percentage radiation-associated toxicity (late)	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.	3 months, 1 year, and 3 years post rPBI
Secondary	Risk of local recurrence (invasive and DCIS)	Cumulative incidence function will be used to estimate local recurrence with death as a competing risk.	3 months, 1 year, and 3 years post rPBI
Secondary	Risk of distant recurrence (invasive and DCIS)	Cumulative incidence function will be used to estimate distant recurrence and distance recurrence with death as a competing risk.	3 months, 1 year, and 3 years post rPBI
Secondary	Location of local recurrence (in-field) (frequency)	Location of recurrence will be summarized by frequency.	3 months, 1 year, and 3 years post rPBI
Secondary	Location of local recurrence (in-field) (percentage)	Location of recurrence will be summarized by percentage.	3 months, 1 year, and 3 years post rPBI
Secondary	Location of local recurrence (out-of-field) (frequency)	Location of recurrence will be summarized by frequency.	3 months, 1 year, and 3 years post rPBI
Secondary	Location of local recurrence (out-of-field) (percentage)	Location of recurrence will be summarized by percentage	3 months, 1 year, and 3 years post rPBI
Secondary	Risk of local recurrence after rPBI requiring mastectomy	Cumulative incidence function will be used to estimate local recurrence after rPBI requiring mastectomy with death as a competing risk	3 months, 1 year, and 3 years post rPBI
Secondary	Invasive breast cancer free survival	Kaplan-Meier method will be used to estimate invasive breast cancer free survival	3 months, 1 year, and 3 years post rPBI
Secondary	Overall survival	Kaplan-Meier method will be used to estimate overall survival	3 months, 1 year, and 3 years post rPBI