Radiotherapy in Preoperative Setting With CyberKnife for Breast Cancer (ROCK)

Radiotherapy in Preoperative Setting With CyberKnife as Treatment in Early Breast Cancer: an Explorative Study

The aim of this study is to prospectively evaluate, in patients affected by early breast cancer, safety and feasibility of single fraction radiotherapy with Cyberknife R in preoperative setting, and to identify factors predictive for outcome based on biologic and clinical parameters.

Study Overview

• Status: Recruiting
• Conditions: Early Breast Cancer
• Intervention / Treatment: Radiation: Neoadjuvant radiotherapy

Detailed Description

Monocentric, open-label, single-arm phase II study evaluating safety and efficacy of neoadjuvant radiotherapy in early breast cancer patients. Patients eligible are women aged 50 or more years old, affected by histologically proven invasive breast cancer, with positive hormonal receptors, grading 1 or 2, HER-2 negative, without lymphovascular invasion, and tumour size up to 2 cm (measured on mammography, ultrasound or magnetic resonance), negative clinical nodal status, eligible for BCS.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lorenzo Livi, Prof; Phone Number: +39 055 7947264; Email: lorenzo.livi@unifi.it
• Study Contact Backup: Name: Icro Meattini, Prof; Phone Number: +39 055 7947264; Email: icro.meattini@unifi.it

Study Locations

• Italy
  • Florence, Italy, 50100
    • Recruiting
    • Azienda Ospedaliero Universitaria Careggi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Signed informed consent
2. Women ≥ 50 years old
3. Histological diagnosis of invasive breast cancer
4. ER positive (≥ 10% of tumoral cells present ER) and/or PR positive (≥ 10% of tumoral cells present PR)
5. Grading 1 or 2
6. Her2 negative (IHC 0-1+; in patients with IHC 2+, absence of amplification at FISH
7. No lymphovascular invasion evidence at biopsy
8. Early breast cancer (T1 N0 M0) clinically and radiologically defined (ultrasound study/ magnetic resonance)
9. Patients eligible for BCS.

Exclusion Criteria:

Extension of breast disease within 5 mm from the skin surface 2. Tumor size > 2 cm 3. Patients affected by collagenopathies 4. Patients with BRCA1/2 mutations 5. Previous irradiation to homolateral breast 6. Previous irradiation to homolateral thoracic wall 7. DCIS and/or Paget's disease 8. Psychiatric disorders preventing informed consent signature.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant radiotherapy arm; Early breast cancer patients eligible for breast conservative surgery will undergo neoadjuvant radiotherapy with Cyberknife robotic system	Radiation: Neoadjuvant radiotherapy; single 21 Gy fraction of Radiotherapy before surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of acute skin toxicity events, measured according to RTOG/EORTC scale	Acute skin toxicity (from the end of radiotherapy to surgery) according to Radiation Therapy Oncology Group (RTOG)/ European Organization for research and treatment of cancer (EORTC) scale. Measuring acute skin toxicity from a minimum of 0 (no change over baseline) to a maximum of 4 (Ulceration, Hemorrage, necrosis)	15 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with pathologic complete response (pCR) after surgery,according to Chevalier score	Rate of pCR according to Chevalier score	30 days
Number of patients with complete resection after surgical excision	Rate of complete resection R0 with margin<1cm (except for deep margin)	30 days
Number of patients free from locoregional progression at 36 months	locoregional progression free survival measured at 36 months	36 months
Number of patients free from metastatic progression at 36 months	Metastasis progression free survival measured at 36 months	36 months
Number of patients dying for breast cancer at 36 months	cause-specific free survival measured at 36 months	36 months
Number of patients dying for any cause at 36 months	global survival measured at 36 months	36 months
Rate of chronic skin toxicity events, measured according to CTCAE	Incidence of chronic skin toxicity (over 90 days since the end of radiotherapy; fibrosis, telangiectasia, tardive oedema) according to Common terminology criteria for adverse events (CTCAE) v 4.03. From a minimum of 1 (Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; to a maximum of 4 (Life-threatening consequences; urgent intervention indicated	90 days
Rate of chronic extra-cutaneous toxicity, measured according to CTCAE	Incidence of chronic extra-skin toxicity (over 90 days from the end of radiotherapy; lung fibrosis, pericarditis, myocardial ischemia, valvulopathy, thoracic wall pain, fracture) according to according to Common terminology criteria for adverse events (CTCAE) v 4.03. From a minimum of 1 (Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; to a maximum of 4 (Life-threatening consequences; urgent intervention indicated	90 days
Correlation of differential genetic expression, immunologic and histopathologic features of tumor sample and biomarkers in blood and urine samples with toxicity and rate of response to radiotheraèy	Radiogenomic: confirm of differential genetic expression of genes already validated in previous literature (30-Radiation- induced gene signature; AOI 16-gene breast signature; IRDS gene signature) with Next Generation Sequencing (NGS, RNA-seq) or Real Time PCR on frozen biopsy tissue. Immunologic: quantitative analysis of infiltrating leucocytes (MS and M1 macrophages, CD8+ and CD4+ lymphocytes) with immunohistochemistry on fresh biopsy tissue Histopathologic: qualitative analyses (pericytes) and quantitative pattern of vascularization in immunohistochemistry. Biochemical: analysis of oxidative stress markers on peripheral blood and urines: a) 1 hour before SBRT; b) 1 hour after SBRT; c) 1 week after SBRT; d) during 24 hours before BCS; e) during 2-4 weeks after BCS.	60 days

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria Careggi
• Investigators: Study Chair: Lorenzo Livi, Prof, AOU Careggi; Study Chair: Icro Meattini, Prof, AOU Careggi; Principal Investigator: Giulio Francolini, MD, AOU Careggi; Principal Investigator: Vanessa Di Cataldo, MD, AOU Careggi

Publications and helpful links

General Publications

• 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.
• Meattini I, Guenzi M, Fozza A, Vidali C, Rovea P, Meacci F, Livi L. Overview on cardiac, pulmonary and cutaneous toxicity in patients treated with adjuvant radiotherapy for breast cancer. Breast Cancer. 2017 Jan;24(1):52-62. doi: 10.1007/s12282-016-0694-3. Epub 2016 Mar 30.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: April 19, 2018
• First Submitted That Met QC Criteria: April 28, 2018
• First Posted (Actual): May 11, 2018

Study Record Updates

• Last Update Posted (Actual): October 22, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: ROCK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes