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出境医 / 临床实验 / Adjuvant Radiotherapy on Circulating Cells in Breast Cancer Patients (CCB-RT)

Adjuvant Radiotherapy on Circulating Cells in Breast Cancer Patients (CCB-RT)

Study Description
Brief Summary:
Radiation applied to the preserved breast during radiotherapy treatment activates numerous molecular cascades in tumor bed adjacent cells causing an inflammatory state. During this process, pre-clinical studies demonstrated CD11b + and CD11b+cKit+cells mobilization in the blood. These cells are involved in numerous processes during tumor progression/control and metastases development. The expected results in clinical setting allow us to investigate the development of innovative therapeutic and monitoring strategies. The clinical repercussions would consist in identifying new predictive and prognostic targets in breast cancer.

Condition or disease Intervention/treatment
Breast Cancer Other: blood samples collection

Detailed Description:

Every year, around one million women are newly diagnosed with breast cancer. Early screening and adjuvant treatments with curative intent such as radiotherapy, hormone therapy, chemotherapy, immunotherapy, have reduced the incidence of breast cancer specific mortality. Despite this, breast cancer remains the main cause of cancer mortality in Europe. The primary cause is due to metastases development in different organs, such as lung, liver, bones and brain. A significant decrease in mortality in breast cancer patients is likely to be achieved by preventing the formation of metastases or by implementing the efficacy of their treatment. Radiotherapy is one of the pillars of breast cancer adjuvant treatments with important survival benefits.

Mutual and dynamic communications between tumor cells and the tumor microenvironment (TME) influence the development and evolution of the tumor as well as the appearance of distant metastases. The mediators of the immune and inflammatory response that constitute TME, as well as mediators of tumor progression, are also considered "targets" of future therapeutic strategies.

Radiation applied to the preserved breast during radiotherapy treatment activates numerous molecular cascades in tumor bed adjacent cells causing an inflammatory state. During this process, pre-clinical studies demonstrated CD11b + and CD11b+cKit+cells mobilization in the blood. These cells are involved in numerous processes during tumor progression/control and metastases development. The results allow us to investigate the development of innovative therapeutic and monitoring strategies. The clinical repercussions would consist in identifying new predictive and prognostic targets in breast cancer.

Study Design
Layout table for study information
Study Type : Observational
Actual Enrollment : 13 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Effects of Adjuvant Radiotherapy on Bone-marrow Derived and Immune Cells in Breast Cancer Patients
Actual Study Start Date : October 25, 2015
Actual Primary Completion Date : September 15, 2020
Actual Study Completion Date : December 30, 2020
Arms and Interventions
Group/Cohort Intervention/treatment
GROUP I/GROUP I bis
20 breast cancer patients who performed radiotherapy treatment
 Other: blood samples collection
blood samples collection are performed at 4 different timepoints: preop, pre rt, week 6 rt, week 12-14 (fu) for GROUP I and GROUP II; blood samples collection are performed at 3 different timepoints: pre rt, week 6 rt, week 12-14 (fu) for GROUP I bis; blood samples collection are performed just once for control GROUP.
GROUP II
maximum 10 patients who performed radiotherapy and chemotherapy and/or immunotherapy and/or neo-adjuvant hormone therapy or/and adjuvant immunotherapy/hormone therapy.
 Other: blood samples collection
blood samples collection are performed at 4 different timepoints: preop, pre rt, week 6 rt, week 12-14 (fu) for GROUP I and GROUP II; blood samples collection are performed at 3 different timepoints: pre rt, week 6 rt, week 12-14 (fu) for GROUP I bis; blood samples collection are performed just once for control GROUP.
CONTROLS GROUP
healthy women with +/- 5 years compared to breast cancer patients age
 Other: blood samples collection
blood samples collection are performed at 4 different timepoints: preop, pre rt, week 6 rt, week 12-14 (fu) for GROUP I and GROUP II; blood samples collection are performed at 3 different timepoints: pre rt, week 6 rt, week 12-14 (fu) for GROUP I bis; blood samples collection are performed just once for control GROUP.
Outcome Measures
Primary Outcome Measures :
  1. the frequency of CD11b⁺cKit⁺ cells in peripheral blood and/or gene expression in circulating CD11b⁺ cells [ Time Frame: pre surgery ]
    validate the hypothesis that adjuvant radiotherapy in breast cancer modulates the frequency of CD11b⁺cKit⁺ cells in peripheral blood and / or gene expression in circulating CD11b⁺ cells, evaluating their trend at different time points compared to radiotherapy treatment.

  2. the frequency of CD11b⁺cKit⁺ cells in peripheral blood and/or gene expression in circulating CD11b⁺ cells [ Time Frame: pre radiotherapy ]
    validate the hypothesis that adjuvant radiotherapy in breast cancer modulates the frequency of CD11b⁺cKit⁺ cells in peripheral blood and / or gene expression in circulating CD11b⁺ cells, evaluating their trend at different time points compared to radiotherapy treatment.

  3. the frequency of CD11b⁺cKit⁺ cells in peripheral blood and/or gene expression in circulating CD11b⁺ cells [ Time Frame: week 6 of radiotherapy ]
    validate the hypothesis that adjuvant radiotherapy in breast cancer modulates the frequency of CD11b⁺cKit⁺ cells in peripheral blood and / or gene expression in circulating CD11b⁺ cells, evaluating their trend at different time points compared to radiotherapy treatment.


Secondary Outcome Measures :
  1. radiotherapy alters in a potentially predictive way the frequency of CD11b⁺cKit⁺ cells in peripheral blood [ Time Frame: week 12-14 (fu) ]
    validate the hypothesis that adjuvant radiotherapy alters in a potentially predictive way the frequency of CD11b⁺cKit⁺ cells in peripheral blood and / or gene expression in circulating CD11b⁺ cells.


Biospecimen Retention:   Samples With DNA
blood samples

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   female
Sampling Method:   Non-Probability Sample
Study Population
patients performing treatments for breast cancer
Criteria

Inclusion Criteria:

  • breast cancer diagnosis bioptically proven with pre-operative clinical stage cT1-4, N0-1, M0;
  • patients who are candidates for conservative surgery (tumorectomy / quadrantectomy +/- lymphadenectomy or sentinel lymph node) or patients already undergoing conservative surgery;
  • patients who are candidates for an adjuvant mammary radiotherapy treatment +/- adjuvant or neoadjuvant chemotherapy due to a triple negative or a high ki67 value that has indicated it;
  • understanding of the Italian language for the Coordinating Center, understanding of the French language for the satellite center.

Exclusion Criteria:

  • previous mastectomy surgery;
  • concomitant cancer diseases;
  • previous chemo / radiotherapy treatments in the last three years.
Contacts and Locations

Locations
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Switzerland
Clinica Luganese Moncucco
Lugano, Ticino, Switzerland, 6900
Sponsors and Collaborators
Clinica Luganese Moncucco
Curzio Rüegg, MD, Head of Department, University of Fribourg
Swiss National Science Foundation
Tsoutsou Pelagia MD, Head of Radation Therapy Department
Investigators
Layout table for investigator information
Principal Investigator: Alessandra Franzetti Pellanda, MD Clinica Luganese Moncucco
Tracking Information
First Submitted Date June 25, 2019
First Posted Date June 28, 2019
Last Update Posted Date April 27, 2021
Actual Study Start Date October 25, 2015
Actual Primary Completion Date September 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 27, 2019)
  • the frequency of CD11b⁺cKit⁺ cells in peripheral blood and/or gene expression in circulating CD11b⁺ cells [ Time Frame: pre surgery ]
    validate the hypothesis that adjuvant radiotherapy in breast cancer modulates the frequency of CD11b⁺cKit⁺ cells in peripheral blood and / or gene expression in circulating CD11b⁺ cells, evaluating their trend at different time points compared to radiotherapy treatment.
  • the frequency of CD11b⁺cKit⁺ cells in peripheral blood and/or gene expression in circulating CD11b⁺ cells [ Time Frame: pre radiotherapy ]
    validate the hypothesis that adjuvant radiotherapy in breast cancer modulates the frequency of CD11b⁺cKit⁺ cells in peripheral blood and / or gene expression in circulating CD11b⁺ cells, evaluating their trend at different time points compared to radiotherapy treatment.
  • the frequency of CD11b⁺cKit⁺ cells in peripheral blood and/or gene expression in circulating CD11b⁺ cells [ Time Frame: week 6 of radiotherapy ]
    validate the hypothesis that adjuvant radiotherapy in breast cancer modulates the frequency of CD11b⁺cKit⁺ cells in peripheral blood and / or gene expression in circulating CD11b⁺ cells, evaluating their trend at different time points compared to radiotherapy treatment.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: June 27, 2019) 		radiotherapy alters in a potentially predictive way the frequency of CD11b⁺cKit⁺ cells in peripheral blood [ Time Frame: week 12-14 (fu) ]
validate the hypothesis that adjuvant radiotherapy alters in a potentially predictive way the frequency of CD11b⁺cKit⁺ cells in peripheral blood and / or gene expression in circulating CD11b⁺ cells.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Adjuvant Radiotherapy on Circulating Cells in Breast Cancer Patients
Official Title Effects of Adjuvant Radiotherapy on Bone-marrow Derived and Immune Cells in Breast Cancer Patients
Brief Summary Radiation applied to the preserved breast during radiotherapy treatment activates numerous molecular cascades in tumor bed adjacent cells causing an inflammatory state. During this process, pre-clinical studies demonstrated CD11b + and CD11b+cKit+cells mobilization in the blood. These cells are involved in numerous processes during tumor progression/control and metastases development. The expected results in clinical setting allow us to investigate the development of innovative therapeutic and monitoring strategies. The clinical repercussions would consist in identifying new predictive and prognostic targets in breast cancer.
Detailed Description

Every year, around one million women are newly diagnosed with breast cancer. Early screening and adjuvant treatments with curative intent such as radiotherapy, hormone therapy, chemotherapy, immunotherapy, have reduced the incidence of breast cancer specific mortality. Despite this, breast cancer remains the main cause of cancer mortality in Europe. The primary cause is due to metastases development in different organs, such as lung, liver, bones and brain. A significant decrease in mortality in breast cancer patients is likely to be achieved by preventing the formation of metastases or by implementing the efficacy of their treatment. Radiotherapy is one of the pillars of breast cancer adjuvant treatments with important survival benefits.

Mutual and dynamic communications between tumor cells and the tumor microenvironment (TME) influence the development and evolution of the tumor as well as the appearance of distant metastases. The mediators of the immune and inflammatory response that constitute TME, as well as mediators of tumor progression, are also considered "targets" of future therapeutic strategies.

Radiation applied to the preserved breast during radiotherapy treatment activates numerous molecular cascades in tumor bed adjacent cells causing an inflammatory state. During this process, pre-clinical studies demonstrated CD11b + and CD11b+cKit+cells mobilization in the blood. These cells are involved in numerous processes during tumor progression/control and metastases development. The results allow us to investigate the development of innovative therapeutic and monitoring strategies. The clinical repercussions would consist in identifying new predictive and prognostic targets in breast cancer.
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
blood samples
Sampling Method Non-Probability Sample
Study Population patients performing treatments for breast cancer
Condition Breast Cancer
Intervention Other: blood samples collection
blood samples collection are performed at 4 different timepoints: preop, pre rt, week 6 rt, week 12-14 (fu) for GROUP I and GROUP II; blood samples collection are performed at 3 different timepoints: pre rt, week 6 rt, week 12-14 (fu) for GROUP I bis; blood samples collection are performed just once for control GROUP.
Study Groups/Cohorts
  • GROUP I/GROUP I bis
    20 breast cancer patients who performed radiotherapy treatment
    Intervention: Other: blood samples collection
  • GROUP II
    maximum 10 patients who performed radiotherapy and chemotherapy and/or immunotherapy and/or neo-adjuvant hormone therapy or/and adjuvant immunotherapy/hormone therapy.
    Intervention: Other: blood samples collection
  • CONTROLS GROUP
    healthy women with +/- 5 years compared to breast cancer patients age
    Intervention: Other: blood samples collection
Publications *
  • Rüegg CR, Chiquet-Ehrismann R, Alkan SS. Tenascin, an extracellular matrix protein, exerts immunomodulatory activities. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7437-41.
  • Lorusso G, Rüegg C. The tumor microenvironment and its contribution to tumor evolution toward metastasis. Histochem Cell Biol. 2008 Dec;130(6):1091-103. doi: 10.1007/s00418-008-0530-8. Epub 2008 Nov 6. Review.
  • Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012 Mar 20;21(3):309-22. doi: 10.1016/j.ccr.2012.02.022. Review.
  • Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002 Dec 19-26;420(6917):860-7. Review.
  • Schlaeppi M, Rüegg C, Trân-Thang C, Chapuis G, Tevaearai H, Lahm H, Sordat B. Role of integrins and evidence for two distinct mechanisms mediating human colorectal carcinoma cell interaction with peritoneal mesothelial cells and extracellular matrix. Cell Adhes Commun. 1997 Mar;4(6):439-55.
  • Boylan AM, Rüegg C, Kim KJ, Hébert CA, Hoeffel JM, Pytela R, Sheppard D, Goldstein IM, Broaddus VC. Evidence of a role for mesothelial cell-derived interleukin 8 in the pathogenesis of asbestos-induced pleurisy in rabbits. J Clin Invest. 1992 Apr;89(4):1257-67.
  • Rüegg C, Pytela R, Erle DJ. Characterization of the leukocyte integrin subunit beta 7. Chest. 1993 Feb;103(2 Suppl):86S.
  • Sharma P, Sahni NS, Tibshirani R, Skaane P, Urdal P, Berghagen H, Jensen M, Kristiansen L, Moen C, Sharma P, Zaka A, Arnes J, Sauer T, Akslen LA, Schlichting E, Børresen-Dale AL, Lönneborg A. Early detection of breast cancer based on gene-expression patterns in peripheral blood cells. Breast Cancer Res. 2005;7(5):R634-44. Epub 2005 Jun 14.
  • Kuonen F, Secondini C, Rüegg C. Molecular pathways: emerging pathways mediating growth, invasion, and metastasis of tumors progressing in an irradiated microenvironment. Clin Cancer Res. 2012 Oct 1;18(19):5196-202. doi: 10.1158/1078-0432.CCR-11-1758. Epub 2012 Jun 22. Review.
  • Drooger JC, Hooning MJ, Seynaeve CM, Baaijens MH, Obdeijn IM, Sleijfer S, Jager A. Diagnostic and therapeutic ionizing radiation and the risk of a first and second primary breast cancer, with special attention for BRCA1 and BRCA2 mutation carriers: a critical review of the literature. Cancer Treat Rev. 2015 Feb;41(2):187-96. doi: 10.1016/j.ctrv.2014.12.002. Epub 2014 Dec 8. Review.
  • Rüegg C, Yilmaz A, Bieler G, Bamat J, Chaubert P, Lejeune FJ. Evidence for the involvement of endothelial cell integrin alphaVbeta3 in the disruption of the tumor vasculature induced by TNF and IFN-gamma. Nat Med. 1998 Apr;4(4):408-14.
  • Han M, Liew CT, Zhang HW, Chao S, Zheng R, Yip KT, Song ZY, Li HM, Geng XP, Zhu LX, Lin JJ, Marshall KW, Liew CC. Novel blood-based, five-gene biomarker set for the detection of colorectal cancer. Clin Cancer Res. 2008 Jan 15;14(2):455-60. doi: 10.1158/1078-0432.CCR-07-1801. Epub 2008 Jan 18.
  • Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, Thürlimann B, Senn HJ; Panel Members. Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. 2015 Aug;26(8):1533-46. doi: 10.1093/annonc/mdv221. Epub 2015 May 4.
  • Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the member states relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Med Etika Bioet. 2002 Spring-Summer;9(1-2):12-9.
  • Dixon JR Jr. The International Conference on Harmonization Good Clinical Practice guideline. Qual Assur. 1998 Apr-Jun;6(2):65-74.
  • [The Helsinki Declaration of the World Medical Association (WMA). Ethical principles of medical research involving human subjects]. Pol Merkur Lekarski. 2014 May;36(215):298-301. Polish.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: April 26, 2021) 		13
Original Estimated Enrollment
 (submitted: June 27, 2019) 		60
Actual Study Completion Date December 30, 2020
Actual Primary Completion Date September 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • breast cancer diagnosis bioptically proven with pre-operative clinical stage cT1-4, N0-1, M0;
  • patients who are candidates for conservative surgery (tumorectomy / quadrantectomy +/- lymphadenectomy or sentinel lymph node) or patients already undergoing conservative surgery;
  • patients who are candidates for an adjuvant mammary radiotherapy treatment +/- adjuvant or neoadjuvant chemotherapy due to a triple negative or a high ki67 value that has indicated it;
  • understanding of the Italian language for the Coordinating Center, understanding of the French language for the satellite center.

Exclusion Criteria:

  • previous mastectomy surgery;
  • concomitant cancer diseases;
  • previous chemo / radiotherapy treatments in the last three years.
Sex/Gender
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: female
Ages 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Not Provided
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number NCT04002570
Other Study ID Numbers CirculatingCellsBreast-RT
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Alessandra Franzetti Pellanda, Clinica Luganese Moncucco
Study Sponsor Clinica Luganese Moncucco
Collaborators
  • Curzio Rüegg, MD, Head of Department, University of Fribourg
  • Swiss National Science Foundation
  • Tsoutsou Pelagia MD, Head of Radation Therapy Department
Investigators
Principal Investigator: Alessandra Franzetti Pellanda, MD Clinica Luganese Moncucco
PRS Account Clinica Luganese Moncucco
Verification Date April 2021

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