Breast Cancer Lung Late Effects (BELLE)

August 21, 2024 updated by: University of Florida

Early Markers of Subclinical Pulmonary Vascular Radiation Toxicity in Breast Cancer

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
41

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32611
        • Department of Radiation Oncology Davis Cancer Pavilion
      • Jacksonville, Florida, United States, 32206
        • University of Florida Health Proton Therapy Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

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.

Description

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 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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).
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.
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 Names:
  • conformal RT

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
2 years
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.
2 years
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).
2 years
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.
2 years
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.
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
8 years
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.
8 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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,
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Florida

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Florida Department of Health

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Walter O'Dell, PhD, University of Florida
  • Principal Investigator: Julie Bradley, PhD, University of Florida

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 14, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 14, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 21, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 28, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 1, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 22, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 21, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB201600387
  • OCR14962 (Other Identifier: UF OnCore)
  • 6BC09 (Other Grant/Funding Number: FL DEPT OF HLTH BANKHEAD-COLEY CANCER RE)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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