Cytokine Expression During Radiation for Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00836186
First received: February 3, 2009
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

To assess the magnitude and frequency of changes in chemo/cytokine expression in women receiving radiation treatment. To asses the impact of race/ethnicity on the magnitude and frequency of changes in chemo/cytokine expression during radiation therapy for breast cancer. And finally to assess the interaction between radiation-induced chemo/cytokine expression changes, and race/ethnicity, with respect to normal tissue reactions to radiation and tumor-associated outcomes.


Condition Intervention
Breast Cancer
Radiation: radiation therapy

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Cytokine Expression During Radiation for Breast Cancer

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • To systematically and quantitatively assess the magnitude and frequency (increases/decreases) of changes in chemo/cytokine (TNFα, PDGF, TGFβ, IL-1, IL-6, IL-8) expression in women receiving radiation therapy for breast cancer. [ Time Frame: 7 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To asses the impact of race/ethnicity on the magnitude and frequency of changes in chemo/cytokine expression during radiation therapy for breast cancer. [ Time Frame: 7 years ] [ Designated as safety issue: No ]
  • To assess the interaction between radiation-induced chemo/cytokine expression changes, and race/ethnicity, with respect to normal tissue reactions to radiation and tumor-associated outcomes. [ Time Frame: 7 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: March 2009
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Radiation: radiation therapy
    Patients will receive whole breast radiation therapy at a dose of 180-200 cGy per fraction for 23-27 fractions to a total dose of 4600 - 4860 cGy. Additional radiation to the lumpectomy bed (Boost) is at the discretion of the treating physician. The total dose to the tumor bed cannot exceed 6600cGy. Treatments will be given Monday through Friday.
Detailed Description:

It is well recognized that the diagnostic and therapeutic gains made in the management of breast cancer over the last 2 decades are not fully realized by all groups. African American women with breast cancer have greater risk of recurrence, shorter overall survival, shorter survival after relapse, worse toxicity and worse cosmetic outcome than their Caucasian counterparts.(1-5) These differences in outcome persist even when controlling for age, and stage at presentation.(1, 6, 7) Being similarly treated with modern breast conserving therapy (lumpectomy and adjuvant whole breast irradiation) at recognized centers of excellence does little to alleviate the disparities in outcomes.(5, 8) Controlling for socioeconomic factors decreases the severity of these disparities, but it does not completely explain them.(4) Theories abound as to the cause of outcome inequality. Many of these theories take either a psychosocial, or biologic bent. One potential biologic cause may be chemokine and cytokine expression.

Chemokines and cytokines (chemo/cytokines) are proteins and peptides used for cell signaling. Primarily secreted by T cells and macrophages, they influence cellular activation, differentiation, and function and act as mediators for inflammatory and immune responses.(9) There has been substantial research linking some of these chemo/cytokines (TNFα, PDGF, TGFβ, Il-6,and IL-8) to tumor promotion and progression. For example, TNFα has been linked to greater cell survival despite genomic injury which in turn leads to greater genetic alterations and malignant transformation. TNFα has been associated with breast cancer progression and metastases.(10) Blocking the receptor for PDGF appears to decrease the metastatic potential of breast cancer cell lines.(11, 12) TGFβ inhibits T cell and B cell lymphocytes and natural killer cell cytotoxicity.(13) This immuno-suppression has been shown to promote tumor progression in mammary cancer cells lines.(13, 14) The ability of TGFβ to promote tumor progression is so well recognized that it has become a therapeutic target by some researchers.(15, 16) IFNγ has been shown to inhibit mammary cancer cell proliferation and angiogenesis in vitro and in vivo.(17) Clinically, Lyon et al reported significantly higher circulating levels of TNFα, Il-6, and IL-8 in women with breast cancer compared to women with a negative breast biopsy.(18) Additionally, researchers have directly correlated increased levels of IL-6 with the development and progression of breast cancer, and decreased overall survival (OAS).(19) Conclusion: Expression of certain chemokines and cytokines is associated with development and progression of breast cancer.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  • Patient must be 18 years of age or older
  • Patients must have histologically confirmed (by routine H&E staining) adenocarcinoma of the breast any T or N No M disease Patients with squamous carcinomas or sarcomas of the breast cancer are NOT eligible
  • Patients must have undergone a segmental mastectomy SM with a level I and ll axillary dissection or sentinel lymph node biopsy Surgical margins at time of local surgery must be negative greater or equal to 2mm for both invasive carcinoma and for non-invasive ductal carcinoma Patients who have post-operative margins which are negative but less than 2mm will be considered eligible if the surgeon states that the margin in question cannot be improved. Patients treated with a mastectomy are NOT eligible
  • Patients must be registered such that radiation therapy begins within 10 weeks of last surgery
  • Patients must have a performance status 0 or 1 by ECOG criteria or a 80-100 Karnofsky Performance Scale at time of consult
  • Patients must not have received prior radiation therapy to the breast at any time for any reason
  • Any patient with active local-regional disease prior to registration is not eligible
  • No other prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer from which the patient has been disease-free for at least 5 years
  • Patients must not be pregnant due to the potential for fetal harm as a result of this treatment regimen. Women of child-bearing potential must use effective non hormonal contraception while undergoing radiation therapy
  • Patients must not have a serious medical or psychiatric illness which prevents informed consent or compliance with treatment
  • All patients must be informed of the investigational nature of this study and give written informed consent in accordance with institutional and federal guidelines
  • Women of all races and ethnic groups are eligible for this trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00836186

Contacts
Contact: Richard Zellars, MD 410-502-1421 zellari@jhmi.edu
Contact: Kelly Szajna, RN, BSN 410-502-9242 kszajna1@jhmi.edu

Locations
United States, Maryland
The Johns Hopkins University School of Medicne Recruiting
Baltimore, Maryland, United States, 21231
Sub-Investigator: Deborah Frassica, MD         
Sub-Investigator: Fariba Asrari, MD         
Sub-Investigator: Leisha Emens, MD         
Sub-Investigator: Kala Visvanathan, MD         
Sub-Investigator: Jeremy Walston, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Richard Zellars, MD The Johns Hopkins University School of Medicine
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00836186     History of Changes
Other Study ID Numbers: J08130, NA_00024399
Study First Received: February 3, 2009
Last Updated: March 28, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on August 28, 2014