Genetic Susceptibility to Radiation-Induced Skin Reactions in Racial/Ethnic Groups of Patients With Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Wake Forest Cancer Center CCOP Research Base
ClinicalTrials.gov Identifier:
NCT01407770
First received: July 30, 2011
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

RATIONALE: Radiation therapy uses high-energy x rays to kill tumor cells. Radiation therapy may cause skin reactions when patients are exposed to high-energy x rays. Studying the genetic pattern of patients before and after radiation therapy may help doctors prevent toxicity and plan the best treatment.

PURPOSE: This clinical trial studies genetic susceptibility to radiation-induced skin reactions in racial/ethnic groups of patients with breast cancer.


Condition Intervention
Breast Cancer
Cognitive Ability, General
Fatigue
Pain
Psychosocial Deprivation
Radiation Toxicity
Skin Abnormalities
Genetic: DNA analysis
Genetic: gene expression analysis
Other: enzyme-linked immunosorbent assay
Other: flow cytometry
Other: laboratory biomarker analysis
Other: questionnaire administration
Procedure: adjuvant therapy
Procedure: assessment of therapy complications
Procedure: quality-of-life assessment
Radiation: 3-dimensional conformal radiation therapy
Radiation: breast irradiation
Radiation: external beam radiation therapy
Radiation: hypofractionated radiation therapy
Radiation: intensity-modulated radiation therapy
Radiation: whole breast irradiation

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Impact of Genomics and Exposures on Disparities in Breast Cancer Radiosensitivity

Resource links provided by NLM:


Further study details as provided by Wake Forest Cancer Center CCOP Research Base:

Primary Outcome Measures:
  • Occurrence of RT-induced early adverse skin reaction (EASR) [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    The primary endpoint is RT-related skin reactions which for consistency and clarity across the study we will use the term "Early Adverse Skin Reaction" (EASR). Skin reactions will be assessed at 4 time points from the start of radiotherapy through 2 months of the post radiotherapy follow-up period. The Modified ONS Criteria for Radiation-Induced Acute Skin Toxicity will be used for classification of EASRs related to the skin. The primary outcome variable will be the occurrence (or not) of RT-induced EASR defined as a grade 4 or higher toxicity (based on the ONS criteria) during the 2 months of the follow-up period of the study.


Secondary Outcome Measures:
  • Quality of life [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Quality of life will be assessed using the FACT-B, a modification of the Skindex-16, and a modified version of the NSABP B39 Quality of Life metric.


Biospecimen Retention:   Samples With DNA

blood and urine samples


Enrollment: 1000
Study Start Date: September 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Genetic: DNA analysis
    Genetic
    Genetic: gene expression analysis
    Genetic
    Other: enzyme-linked immunosorbent assay
    Genetic
    Other: flow cytometry
    Genetic
    Other: laboratory biomarker analysis
    Genetic
    Other: questionnaire administration
    Genetic
    Procedure: adjuvant therapy
    Genetic
    Procedure: assessment of therapy complications
    Genetic
    Procedure: quality-of-life assessment
    Genetic
    Radiation: 3-dimensional conformal radiation therapy
    Genetic
    Radiation: breast irradiation
    Genetic
    Radiation: external beam radiation therapy
    Genetic
    Radiation: hypofractionated radiation therapy
    Genetic
    Radiation: intensity-modulated radiation therapy
    Genetic
    Radiation: whole breast irradiation
    Genetic
Detailed Description:

OBJECTIVES:

  • To develop and validate prediction biomarkers for radiation therapy (RT)-induced acute and chronic skin reactions and quality of life in five racial/ethnic groups of breast cancer patients, Whites*, Black/African Americans, Hispanic/Latinos, Asians/Native Hawaiians/Pacific Islanders, and American Indians/Alaskan Natives. NOTE: *This stratum is closed as of April 25, 2012.
  • To develop polygenic models of RT-induced skin reactions with a comprehensive evaluation of genome-wide nonsynonymous single nucleotide polymorphisms (nsSNPs).
  • To evaluate the levels of DNA damage (Comet assay) and radiosensitivity (Cell Cycle G2 Delay assay) in lymphocytes before and after RT.
  • To test the effect of gene-gene and gene-smoking interactions on RT-induced skin reactions.
  • To assess race-ethnic differences in RT-induced skin reactions, DNA damage, and radiosensitivity and to determine if the gene effects are consistent across race-ethnicity (gene-race/ethnic interactions).

OUTLINE: This is a multicenter study. Patients are stratified according to race/ethnicity (Whites* vs Black/African Americans vs Hispanic/Latinos vs Asians/Native Hawaiians/Pacific Islanders vs American Indians/Alaskan Natives). NOTE: *This stratum is closed as of April 25, 2012.

Patients undergo adjuvant radiotherapy after breast-conserving surgery.

Blood and urine samples are collected at baseline and last day of radiotherapy for genotyping, DNA damage, cell cycle assays, urine cotinine, inflammatory immune response biomarkers, and tumor-killing activity by BeadArray System, Comet assay, flow cytometry-based assay, Cell-Cycle G2 Delay Assay, Oxygen Radical Absorbance Capacity (ORAC) assay, and ELISA.

Patients are assessed for acute toxicity by research staff using the ONS Criteria for Radiation-Induced Acute Skin Toxicity at baseline, week 3, and at 1 and 2 months after radiotherapy. Patients are also assessed for chronic toxicity by research staff using the Chronic skin toxicity questionnaire (RTOG SOMA Criteria for RT- Induced Breast/Chest Wall Late Skin Toxicity) at 6 and 12 months after completion of radiotherapy. Photographs of the breast, chest wall, and contralateral breast are also taken at baseline, week 3, last day of radiotherapy, and at 1, 2, 6, and 12 months after completion of radiotherapy.

Patients complete the Breast Cancer Risk Study Questionnaire, the Functional Assessment of Cancer Therapy Breast (FACT-B), the Modified Skindex, and the B39 Quality-of-Life (QOL) Questionnaire at baseline, last day of radiotherapy, and at 1, 2, 6, and 12 months after radiotherapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Race/ethnicity to include Whites*, Black/African Americans (AA), Hispanic/Latinos, Asians/Native Hawaiians/Pacific Islanders, and Native American or Alaskan

Criteria

DISEASE CHARACTERISTICS:

  • Female patients newly diagnosed with breast carcinoma including ductal carcinoma in situ (DCIS)

    • Stage 0-IIIA disease
  • Status post-lumpectomy, -quadrantectomy, or -mastectomy
  • Plan to receive adjuvant radiation to the whole breast or chest wall and/or regional lymph nodes
  • No sites that cannot send blood/urine specimens to Wake Forest by overnight (next day) express shipping

PATIENT CHARACTERISTICS:

  • *This stratum is closed as of April 25, 2012.
  • No patients who do not understand English and are unable to complete form with assistance

PRIOR CONCURRENT THERAPY:

  • Total dose > 40 Gy, dose per fraction > 1.8 - 2.0 Gy, use of 2D, 3D-conformal, or intensity-modulated radiation therapy (IMRT) treatment techniques allowed; a daily fraction of 2.7 Gy to the whole breast is suggested for hypofractionated regimens
  • Concurrent and sequential boost techniques are allowed for both standard and hypofractionated regimens
  • Adjuvant hormonal therapy will be allowed prior to, during, and/or after radiotherapy (RT) at the discretion of a medical oncologist
  • Targeted therapies, such as Herceptin, will be allowed prior to, during, and/or after RT at the discretion of the medical oncologist
  • No prior radiation to the involved breast or chest wall
  • No concurrent chemotherapy
  • No patients who underwent breast reconstruction following mastectomy

    • Placement of tissue expanders and implants are not allowed
  • No patients who have undergone MammoSite® or any other form of brachytherapy as well as those who will be treated with skin-sparing IMRT
  • Patients may not be concurrently enrolled in a protocol that involves treatment of the skin, i.e., applying lotions/moisturizers

    • Protocols that do not involve treatment of the skin are allowed
  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: NCT01407770

Locations
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
Sponsors and Collaborators
Wake Forest Cancer Center CCOP Research Base
Investigators
Principal Investigator: James J. Urbanic, MD Comprehensive Cancer Center of Wake Forest University
  More Information

Additional Information:
No publications provided

Responsible Party: Wake Forest Cancer Center CCOP Research Base
ClinicalTrials.gov Identifier: NCT01407770     History of Changes
Other Study ID Numbers: CCCWFU97609, U10CA081851
Study First Received: July 30, 2011
Last Updated: December 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Wake Forest Cancer Center CCOP Research Base:
radiation toxicity
skin reactions secondary to radiation therapy
pain
fatigue
psychosocial effects of cancer and its treatment
depression
cognitive/functional effects
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage IIIA breast cancer
ductal breast carcinoma in situ

Additional relevant MeSH terms:
Congenital Abnormalities
Breast Neoplasms
Fatigue
Skin Abnormalities
Radiation Injuries
Genetic Predisposition to Disease
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Signs and Symptoms
Wounds and Injuries
Disease Susceptibility
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on July 24, 2014