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

Primary Purpose

Early Breast Cancer

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Neoadjuvant radiotherapy
Sponsored by
Azienda Ospedaliero-Universitaria Careggi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Early Breast Cancer

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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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Sites / Locations

  • Azienda Ospedaliero Universitaria CareggiRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant radiotherapy arm

Arm Description

Early breast cancer patients eligible for breast conservative surgery will undergo neoadjuvant radiotherapy with Cyberknife robotic system

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Number of patients with pathologic complete response (pCR) after surgery,according to Chevalier score
Rate of pCR according to Chevalier score
Number of patients with complete resection after surgical excision
Rate of complete resection R0 with margin<1cm (except for deep margin)
Number of patients free from locoregional progression at 36 months
locoregional progression free survival measured at 36 months
Number of patients free from metastatic progression at 36 months
Metastasis progression free survival measured at 36 months
Number of patients dying for breast cancer at 36 months
cause-specific free survival measured at 36 months
Number of patients dying for any cause at 36 months
global survival measured at 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
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
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.

Full Information

First Posted
April 19, 2018
Last Updated
October 18, 2019
Sponsor
Azienda Ospedaliero-Universitaria Careggi
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1. Study Identification

Unique Protocol Identification Number
NCT03520894
Brief Title
Radiotherapy in Preoperative Setting With CyberKnife for Breast Cancer
Acronym
ROCK
Official Title
Radiotherapy in Preoperative Setting With CyberKnife as Treatment in Early Breast Cancer: an Explorative Study
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2018 (Actual)
Primary Completion Date
May 1, 2022 (Anticipated)
Study Completion Date
May 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Ospedaliero-Universitaria Careggi

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Early Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Neoadjuvant radiotherapy arm
Arm Type
Experimental
Arm Description
Early breast cancer patients eligible for breast conservative surgery will undergo neoadjuvant radiotherapy with Cyberknife robotic system
Intervention Type
Radiation
Intervention Name(s)
Neoadjuvant radiotherapy
Intervention Description
single 21 Gy fraction of Radiotherapy before surgery
Primary Outcome Measure Information:
Title
Rate of acute skin toxicity events, measured according to RTOG/EORTC scale
Description
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)
Time Frame
15 days
Secondary Outcome Measure Information:
Title
Number of patients with pathologic complete response (pCR) after surgery,according to Chevalier score
Description
Rate of pCR according to Chevalier score
Time Frame
30 days
Title
Number of patients with complete resection after surgical excision
Description
Rate of complete resection R0 with margin<1cm (except for deep margin)
Time Frame
30 days
Title
Number of patients free from locoregional progression at 36 months
Description
locoregional progression free survival measured at 36 months
Time Frame
36 months
Title
Number of patients free from metastatic progression at 36 months
Description
Metastasis progression free survival measured at 36 months
Time Frame
36 months
Title
Number of patients dying for breast cancer at 36 months
Description
cause-specific free survival measured at 36 months
Time Frame
36 months
Title
Number of patients dying for any cause at 36 months
Description
global survival measured at 36 months
Time Frame
36 months
Title
Rate of chronic skin toxicity events, measured according to CTCAE
Description
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
Time Frame
90 days
Title
Rate of chronic extra-cutaneous toxicity, measured according to CTCAE
Description
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
Time Frame
90 days
Title
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
Description
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.
Time Frame
60 days

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Women
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent Women ≥ 50 years old Histological diagnosis of invasive breast cancer ER positive (≥ 10% of tumoral cells present ER) and/or PR positive (≥ 10% of tumoral cells present PR) Grading 1 or 2 Her2 negative (IHC 0-1+; in patients with IHC 2+, absence of amplification at FISH No lymphovascular invasion evidence at biopsy Early breast cancer (T1 N0 M0) clinically and radiologically defined (ultrasound study/ magnetic resonance) Patients eligible for BCS. Exclusion Criteria: Extension of breast disease within 5 mm from the skin surface 2. Tumor size &gt; 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. -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lorenzo Livi, Prof
Phone
+39 055 7947264
Email
lorenzo.livi@unifi.it
First Name & Middle Initial & Last Name or Official Title & Degree
Icro Meattini, Prof
Phone
+39 055 7947264
Email
icro.meattini@unifi.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lorenzo Livi, Prof
Organizational Affiliation
AOU Careggi
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Icro Meattini, Prof
Organizational Affiliation
AOU Careggi
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Giulio Francolini, MD
Organizational Affiliation
AOU Careggi
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Vanessa Di Cataldo, MD
Organizational Affiliation
AOU Careggi
Official's Role
Principal Investigator
Facility Information:
Facility Name
Azienda Ospedaliero Universitaria Careggi
City
Florence
ZIP/Postal Code
50100
Country
Italy
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27025498
Citation
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.
Results Reference
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PubMed Identifier
25605582
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.
Results Reference
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Radiotherapy in Preoperative Setting With CyberKnife for Breast Cancer

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