Accelerated Partial Breast Irradiation Versus Standard or Hypofractionated Whole-Breast Irradiation, in Early Breast Cancer, After Breast-conserving Surgery

Malignant Neoplasm of Breast Clinical Trial

— LAPIDARY  

Official title:

Clinical Trial, Randomized, Open Label, With an Active Comparator to Assess the Efficacy and Safety of Using Accelerated Partial Irradiation Versus Standard or Hypofractionated Irradiation of the Entire Breast in Patients With Initial Breast Cancer After Conservative Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04669873
• Other study ID #: 38341220.8.0000.0072
• Status: Recruiting
• Phase: N/A
• Start date: March 4, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: November 2020
• Source: Instituto Brasileiro de Controle do Cancer
• Contact: Eduardo Barbieri
• Phone: +551198639-1945
• Email: edurxt[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Radiotherapy has been confirmed as an important treatment breast-conserving surgery reducing the risk of any recurrence of breast cancer and breast cancer-related mortality in patients with early breast cancer. There are no comparative data on the ideal radiotherapy treatment regimen for patients with early stage breast cancer who underwent conservative surgery in the Brazilian population.

Description:

The investigators propose a prospective, randomized, pilot study, with active control, to evaluate the viability and safety of accelerated partial breast irradiation, in 5 fractions, comparing with the radiotherapy regimens of the whole breast in 15 and 5 fractions, in patients with breast cancer, in initial stage, who underwent conservative surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: December 31, 2026
• Est. primary completion date: December 7, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years to 90 Years

Eligibility

Inclusion Criteria:

• Information to the patient and signed informed consent;
• Women aged =50 years
• Breast conserving surgery
• Pathologic tumor size < 3 cm (maximum microscopic diameter of the invasive component)
• Invasive adenocarcinoma (except classic invasive lobular carcinoma)
• Unifocal disease
• Histopathologic grades I or II
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Lymphovascular invasion absent
• Negative axillary lymph nodes
• Minimum microscopic margins of non-cancerous tissue of 2mm (excluding deep margin when in deep fascia)
• No prior breast or mediastinal radiotherapy
• No hematogenous metastases

Exclusion Criteria:

• Previous malignancy (except non-melanomatous skin cancer)
• Mastectomy
• Classical-Type Invasive Lobular Carcinoma
• Neoadjuvant chemotherapy
• Human Epidermal growth factor Receptor-type 2 positive (HER2+)
• Triple-negative breast cancers
• Intravascular lymphoma present
• Contraindications to radiotherapy.
• No geographical, social or psychologic reasons that would prevent study follow

Related Conditions & MeSH terms

• Breast Neoplasms
• Malignant Neoplasm of Breast
• Neoplasms

Intervention

Radiation:
• Active Comparator: Standard
Radiation: Whole Breast Irradiation + Boost Whole breast, either 40Gy, in 15 fractions, in 3 weeks
• Experimental 1: Hypofractionated radiotherapy
Radiation: Hypofractionated irradiation Whole Breast Irradiation 26Gy in 5 fractions in one week
• Experimental 2: Accelerated Partial Breast Irradiation
Radiation: Accelerated partial breast irradiation Tumor bed 26Gy in 5 fractions, in 5 days.

Locations

Country	Name	City	State
Brazil	IBCC Oncologia	Sao Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Brasileiro de Controle do Cancer

Country where clinical trial is conducted

Brazil, 

References & Publications (11)

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

Coles CE, Griffin CL, Kirby AM, Titley J, Agrawal RK, Alhasso A, Bhattacharya IS, Brunt AM, Ciurlionis L, Chan C, Donovan EM, Emson MA, Harnett AN, Haviland JS, Hopwood P, Jefford ML, Kaggwa R, Sawyer EJ, Syndikus I, Tsang YM, Wheatley DA, Wilcox M, Yarnold JR, Bliss JM; IMPORT Trialists. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet. 2017 Sep 9;390(10099):1048-1060. doi: 10.1016/S0140-6736(17)31145-5. Epub 2017 Aug 2. — View Citation

Correa C, Harris EE, Leonardi MC, Smith BD, Taghian AG, Thompson AM, White J, Harris JR. Accelerated Partial Breast Irradiation: Executive summary for the update of an ASTRO Evidence-Based Consensus Statement. Pract Radiat Oncol. 2017 Mar - Apr;7(2):73-79. doi: 10.1016/j.prro.2016.09.007. Epub 2016 Sep 17. — View Citation

Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011 Nov 12;378(9804):1707-16. doi: 10.1016/S0140-6736(11)61629-2. Epub 2011 Oct 19. Review. — View Citation

Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, Dobbs HJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Simmons S, Sydenham MA, Venables K, Bliss JM, Yarnold JR; START Trialists' Group. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol. 2013 Oct;14(11):1086-1094. doi: 10.1016/S1470-2045(13)70386-3. Epub 2013 Sep 19. — View Citation

Imielinski K. [Sexuality and personality]. Ginekol Pol. 1981 Mar;52(3):293-7. Polish. — View Citation

Livi L, Meattini I, Marrazzo L, Simontacchi G, Pallotta S, Saieva C, Paiar F, Scotti V, De Luca Cardillo C, Bastiani P, Orzalesi L, Casella D, Sanchez L, Nori J, Fambrini M, Bianchi S. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer. 2015 Mar;51(4):451-463. doi: 10.1016/j.ejca.2014.12.013. Epub 2015 Jan 17. — View Citation

Olivotto IA, Whelan TJ, Parpia S, Kim DH, Berrang T, Truong PT, Kong I, Cochrane B, Nichol A, Roy I, Germain I, Akra M, Reed M, Fyles A, Trotter T, Perera F, Beckham W, Levine MN, Julian JA. Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol. 2013 Nov 10;31(32):4038-45. doi: 10.1200/JCO.2013.50.5511. Epub 2013 Jul 8. — View Citation

Polgár C, Fodor J, Major T, Sulyok Z, Kásler M. Breast-conserving therapy with partial or whole breast irradiation: ten-year results of the Budapest randomized trial. Radiother Oncol. 2013 Aug;108(2):197-202. doi: 10.1016/j.radonc.2013.05.008. Epub 2013 Jun 3. — View Citation

Strnad V, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, Lyczek J, Guinot JL, Dunst J, Gutierrez Miguelez C, Slampa P, Allgäuer M, Lössl K, Polat B, Kovács G, Fischedick AR, Wendt TG, Fietkau R, Hindemith M, Resch A, Kulik A, Arribas L, Niehoff P, Guedea F, Schlamann A, Pötter R, Gall C, Malzer M, Uter W, Polgár C; Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet. 2016 Jan 16;387(10015):229-38. doi: 10.1016/S0140-6736(15)00471-7. Epub 2015 Oct 19. — View Citation

Veronesi U, Orecchia R, Maisonneuve P, Viale G, Rotmensz N, Sangalli C, Luini A, Veronesi P, Galimberti V, Zurrida S, Leonardi MC, Lazzari R, Cattani F, Gentilini O, Intra M, Caldarella P, Ballardini B. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013 Dec;14(13):1269-77. doi: 10.1016/S1470-2045(13)70497-2. Epub 2013 Nov 11. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of local recurrence	To estimate and compare the rate of local recurrence between the experimental and control arms.	5 years
Secondary	Time to occurrence of distant metastases	Distant tumor time is defined as number of days from randomization until occurrence of distant metastases, death without prior distant progression, or end of follow-up.	5 years
Secondary	Disease-free survival	Disease-free survival, defined as number of days from randomization until the first occurrence of local recurrence, distant metastases, tumor-related death, death without prior progression, or end of follow-up.	5 years
Secondary	Overall survival	Overall survival time, defined as number of days from randomization until death or end of follow-up.	5 years
Secondary	Medico-economic study	To evaluate and compared the cost between Accelerated Partial Breast Irradiation with Standard and Hypofractionated irradiation	Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end
Secondary	Health-related Quality of Life	To evaluate the patients quality of life with the help of the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). This questionnaire was designed to be cancer specific, multidimensional in structure, suitable for self-administration (brief and easy to complete), and applicable in a wide range of cultural contexts. The scores in each dimension are uniformly transformed to dimensions ranging from 0 to 100, with 0 denoting the negative (low functioning, high symptom burden) and 100 the positive end (high functioning, low symptom burden) of the continuum.	Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end
Secondary	Evaluation of quality of life change by European Organization for Research and Treatment of Cancer Breast-Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23)	To evaluate the patient quality of life with the help of the European Organization for Research and Treatment of Cancer Breast-Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23). The 23-item EORTC QLQ BR23 contains two breast cancer specific functional scales (body image and sexuality) and three symptom scales evaluating arm symptoms, breast symptoms, and systemic therapy symptoms. The minimum and maximum values are 0 and 100, and higher scores mean a better outcome.	Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end
Secondary	Fatigue Questionnaire (Functional Assessment of Cancer Therapy-Fatigue - FACT-F)	To evaluate the patient quality of life with the help of the Functional Assessment of Cancer Therapy-Fatigue (FACT-F). Scores are interpreted according to the guidelines of the Scoring Manual. The higher the number of points, the better the quality of life. To obtain the score, the negative questions are reverted; then the answers of the domains are added up, and a proportional average is carried out in case of non answered items.	Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end
Secondary	Measurement Satisfaction of Body Image of the participants	To evaluate the patient quality of life and patient satisfaction with the help of the Body Image Scale (BIS). Scores are interpreted according to the guidelines of the Scoring Manual. The Body Image Scale (BIS) is a self-assessment scale designed to assess cancer patients' perceptions of their appearance and identify any changes to those perceptions resulting from a disease or a treatment. The total score ranges from 0 to 30. A higher score means a higher level of body image disturbance.	Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end
Secondary	Changes in anxiety and depression	To evaluate the patient quality of life and patient satisfaction with the help of the Hospital Anxiety and Depression Scale (HADS). Scores for each sub scale (depression and anxiety) are summed-up and range from 0 to 21. Values from 0-7 indicate normal levels, 8-10 are border values and values from 11-21 are considered to be pathological.	Baseline and 3 months, 6 months, 12 months, 2 years, 5 years after treatment end
Secondary	Early and late adverse effects in normal tissues	To evaluate the results reported by patient and evaluated by doctors, as well as, photographic assessments.	5 years
Secondary	Late adverse effects	To evaluate if the patient had symptoms of swelling or edema in the arm, breast shrinkage, hardness, pigmentation, necrosis, pain and tenderness in the breast.	5 years
Secondary	Acute toxicity rate	To evaluate acute toxicity rate. The maximum grade for acute toxicity will be recorded for each patient at each treatment evaluation using Common Terminology Criteria for Adverse Events.	5 years