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Breast Cancer Lung Late Effects (BELLE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2016 by University of Florida
Sponsor:
Collaborator:
Florida Department of Health
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT02725840
First received: March 21, 2016
Last updated: December 13, 2016
Last verified: December 2016
  Purpose

Through improved early detection and treatment, the number of long term breast cancer survivors continues to increase. There are now 2.8 million breast cancer survivors in the U.S. Florida alone adds over 9,000 women to the survivorship pool each year. Most receive radiation treatment (RT) of the affected breast and chest wall to reduce risk of recurrence. Even with advanced radiation techniques for dose conformality to minimize exposure of the highly sensitive lung, 14% of breast cancer patients treated with radiation develop clinical pulmonary toxicity, with 4% overall experiencing high grade clinical toxicity. Early diagnosis and intervention to mitigate lung radiation toxicity is increasingly important for the long term care of these survivors.

The investigators' goal is to better identify breast cancer patients at high risk for experiencing severe pulmonary toxicity requiring medical intervention, provide a means to identify toxicity early on, and tailor treatment and/or early intervention on a per-patient basis.


Condition Intervention
Radiation Injury
Breast Cancer
Radiation: Proton beam radiation therapy.
Radiation: X-ray based radiation therapy
Procedure: Computed Tomography (CT) Scan
Procedure: Pulmonary Function Test (PFT)

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Early Markers of Subclinical Pulmonary Vascular Radiation Toxicity in Breast Cancer

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • The lower dose limit for measurable change in number of small blood vessels as characterized from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy. [ Time Frame: 2 years ]
    The investigators seek to identify differences between the treatment modalities (proton versus X-ray) in regards to the lower dose limits for change in number of small blood vessels as measured from chest CT scans and quantified using the team's analysis technique.

  • Vessel number change dose-response relationship as measured from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy. [ Time Frame: 2 years ]
    Identify change in number of small blood vessels as measured from chest CT scans and quantified using the team's analysis technique, as a function of radiation dose exposure across the lung.

  • Recovery of number of small blood vessels as measured from chest CT scans acquired at 1,3,6, 12 and 24 months (= 2 years) and compared between proton versus X-ray radiation therapy. [ Time Frame: 2 years ]
    Identify differences in temporal patterns of vessel regeneration following radiation exposure as a function of dose and of modality (proton versus X-ray).

  • Temporal patterns of blood cytokines following radiation exposure as measured from blood draws a pre-treatment and at 1,3,6, 12 and 24 months (= 2 years), and compared between proton versus X-ray radiation therapy. [ Time Frame: 2 years ]
    Quantify differences in temporal patterns of levels of cytokines in the blood in breast cancer patients receiving conventional X-ray versus proton RT using serial blood draws that are time-matched with the CT chest scans.

  • Correlate change in number of small blood vessels as measured from chest CT scans at 1,3,6, 12 and 24 months (= 2 years) with clinical pulmonary function test outcomes at 6 and 12 months. [ Time Frame: 1 year ]
    Correlate change in number of small blood vessels as measured from chest CT scans and quantified using the team's analysis technique, with clinical pulmonary function test (spirometry and diffusion capacity for carbon monoxide) outcomes to identify potential predictive value of early vascular changes to conventional clinical measures of late effects.


Secondary Outcome Measures:
  • Compare incidence of long-term clinical grade 2 and higher radiation toxicity to the lung as documented in patient medical records and compared between proton versus X-ray radiation therapy. [ Time Frame: 8 years ]
    The goal is to monitor long-term (>8 year) incidence of clinical pulmonary toxicity in these subjects to identify any difference between X-ray and proton treatment methodologies.

  • Compare duration of overall survival and whether death was attributed to lung radiation toxicity as documented in patient medical records and compared between proton versus X-ray radiation therapy. [ Time Frame: 8 years ]
    The goal is to monitor long-term (>8 year) survival in these subjects to identify any difference between X-ray and proton treatment methodologies.


Other Outcome Measures:
  • Document patterns of metastatic presentation as observed from chest CT scans at 1,3,6, 12 and 24 months (= 2 years). [ Time Frame: 2 years ]
    To identify patterns of asymptomatic metastatic progression in those subjects who develop recurrence to the thorax during the follow-up imaging period,


Biospecimen Retention:   Samples With DNA
blood plasma collection

Estimated Enrollment: 55
Study Start Date: May 2016
Estimated Study Completion Date: April 2021
Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Proton beam radiation therapy
The participants in this group will be receiving proton therapy of the affected breast and chest wall as part of their standard of care. In addition, a Computed Tomography (CT) Scan of the chest wall will be performed, and pulmonary function test (PFT).
Radiation: Proton beam radiation therapy.
Proton bean radiation therapy interact differently with tissue with the result that protons are absorbed completely within the tissue instead of primarily passing through the entire body. The maximal depth of penetration is dependent upon the incoming velocity (energy) of the protons. Proton therapy utilizes this property to deliver radiation with very little dose beyond the targeted lesion. The dose-rate will be managed as part of the standard of care.
Other Name: PTI
Procedure: Computed Tomography (CT) Scan
Computed Tomography (CT) Scan of the chest will be performed at 1, 3, 6, 12, 18 and 24 months
Procedure: Pulmonary Function Test (PFT)
Pulmonary function test (PFT) will be performed at pre-treatment, and at 6 and 12 months.
X-ray based radiation therapy
The participants in this group will be receiving X-ray radiation therapy of the affected breast and chest wall as part of their standard of care. In addition, a Computed Tomography (CT) Scan of the chest wall will be performed, and pulmonary function test (PFT).
Radiation: X-ray based radiation therapy
The three-dimensional (3D) mapping of radiation dose distributions permits detailed assessment of local vascular damage as a function of treatment factors of dose, dose-rate. The dose-rate will be managed as part of the standard of care.
Other Name: conformal RT
Procedure: Computed Tomography (CT) Scan
Computed Tomography (CT) Scan of the chest will be performed at 1, 3, 6, 12, 18 and 24 months
Procedure: Pulmonary Function Test (PFT)
Pulmonary function test (PFT) will be performed at pre-treatment, and at 6 and 12 months.

Detailed Description:

This project involves repeat chest computed tomography (CT) imaging and blood draws in subjects with breast cancer with radiation treatment to the affected breast and chest wall. The investigators are studying women receiving one of 2 types of radiation, either conventional X-rays (IMRT) or protons at the University of Florida Health Proton Therapy Institute (UFHPTI). These subjects typically would not receive follow-up chest CTs as per standard of care. All subjects will have received a pre-treatment chest CT scan as part of the treatment planning process. The investigators will enroll 30 subjects in the X-ray treatment group and 25 subjects in the proton group.

The investigative team has recently solved the technical challenges of extracting and characterizing lung vascular anatomy from clinical CT images of the chest and used these tools to characterize acute and chronic changes to pulmonary vascular structure in breast cancer patients receiving radiation to the chest wall for treatment of their cancer.

In Aim 1 of this study the investigators will compare lung vascular damage in women treated with conventional radiation with those treated at the UFHPTI. In Aim 2 they will use blood samples of the subjects of Aim 1 to investigate the differential role of inflammatory cytokines in the initiation and progression of pulmonary vascular radiation response in conventional versus proton radiation exposures. Aim 3 compares vascular damage with clinical pulmonary function assessment using spirometry and diffusion capacity of carbon monoxide (DLCO). Aim 4 ties together Aims 1-3 by employing and extending existing mathematical models of radiobiological response to improve and solidify the scientific understanding of the biological mechanisms of radiation response.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Breast cancer patients who are 18 years of age or older and have Stage II or higher disease and who are scheduled to receive conventional X-ray RT (n=30) or proton therapy (n=25) to the breast and chest wall for the treatment of breast cancer will be enrolled in this study.
Criteria

Inclusion Criteria:

  • Women who are at least 18 years of age.
  • Women with Stage II or higher primary breast cancer and who are scheduled to receive conventional X-ray RT (n=30) or proton therapy (n=25) to the breast and chest wall.

Exclusion Criteria:

  • Patients not willing or able to submit to repeat chest CT scans with injected vascular contrast and blood draws.
  • Pregnant women.
  • Patients who have previously had radiation treatment where any portion of the lung received greater than 5 Gy of radiation exposure.
  • Women with bilateral breast cancer or metastatic disease to sites near the chest where additional radiation exposure to any portion of the lung of greater than 5 Gy is anticipated.
  • Women with allergic reaction to all common CT contrast agents.
  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: NCT02725840

Locations
United States, Florida
Department of Radiation Oncology Davis Cancer Pavilion Recruiting
Gainesville, Florida, United States, 32611
Contact: John M Lybarger, MPH    352-265-0680 ext 87829    lybarj@shands.ufl.edu   
Principal Investigator: Walter O'Dell, PhD         
Sub-Investigator: Karen Daily, DO         
Sub-Investigator: Judith Lightsey, MD         
Sub-Investigator: Coy Heldermon, MD, PhD         
Sub-Investigator: David Wymer, MD         
Sub-Investigator: Fei Zou, PhD         
Sub-Investigator: Paul Okunieff, MD         
Sub-Investigator: Jorge Lascano, MD         
University of Florida Health Proton Therapy Institute Not yet recruiting
Jacksonville, Florida, United States, 32206
Contact: Julie Bradley, MD    904-588-1800    jbradley@floridaproton.org   
Contact: Ashley Williams, BA, CCRP    (904) 588-1451    awilliams@floridaproton.org   
Sub-Investigator: Nancy Mendenhall, MD         
Sub-Investigator: Christopher Klassen, MD, PhD         
Sub-Investigator: Michael Rutenberg, MD         
Sub-Investigator: Roi Dagan, MD, MS         
Principal Investigator: Julie Bradley         
Sponsors and Collaborators
University of Florida
Florida Department of Health
Investigators
Principal Investigator: Walter O'Dell, PhD University of Florida
Principal Investigator: Julie Bradley, PhD University of Florida
  More Information

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02725840     History of Changes
Other Study ID Numbers: IRB201600387
Study First Received: March 21, 2016
Last Updated: December 13, 2016
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by University of Florida:
pulmonary vasculature
radiation late effects
proton therapy

Additional relevant MeSH terms:
Breast Neoplasms
Radiation Injuries
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Wounds and Injuries

ClinicalTrials.gov processed this record on April 26, 2017