Breast CancerPhase 1/2NCT00581256
A Randomized Comparison of Radiation Therapy Techniques in the Management of Node Positive Breast Cancer
A Phase 1/2 study testing IMRT and 3D in people with Breast Cancer, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
Radiotherapy has been shown to reduce breast-cancer specific mortality in patients at high risk for distant dissemination. It has also been shown to increase rates of non-breast cancer deaths and morbidity due to cardiovascular and pulmonary toxicity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- IMRT and 3D
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2006to Apr 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eligibility Criteria
- Breast cancer diagnosis: Patients must have histologically confirmed adenocarcinoma of the breast requiring comprehensive loco-regional irradiation that includes treatment to the intact breast/chest wall, supraclavicular (SCV), infraclavicular nodes (ICV), and internal mammary nodes (IMN).
- Patients must have pathologic T 1, 2, 3 or 4, N 1, 2, or 3 Stage II or III disease as defined by the AJCC Staging System, 6th edition. Patients who do not undergo axillary staging but are at risk for nodal involvement may also be treated.
- All patients must have left-sided breast cancer.
- Both men and women are eligible.
- Patients must be adults (18 years of age or older)
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- For women of child-bearing age, effective contraception must be used. A written statement must be obtained that the patient is not pregnant. If there is any question of pregnancy at time of therapeutic RT or at time of each SPECT-CT scan, a pregnancy test will be done to confirm the patient is not pregnant.
- Performance status should be 0-2 by ECOG criteria.
- Patients that have received prior RT may be enrolled on the present study if the new breast lesion can be treated with no overlap of RT fields.
- Patients must be aware of the neoplastic nature of her/his disease.
- Patients must be informed of the investigational nature of this study and must sign an informed consent in accordance with the Institutional Review Board (IRB) of the University of Michigan and federal guidelines.
- Patients' blood tests should indicate they are able to tolerate radiotherapy. Tests must be done within 28 days of registration:
- CBC with differential and platelet count (Hemoglobin > 8.0 g/dl; wbc > 2000/mm3; absolute neutrophil count > 1000/mm3; platelet count > 75,000/mm3.
Who cannot join
- Patients who are pregnant or are nursing are excluded.
- Pathologically node negative breast cancer unless treated with neo-adjuvant chemotherapy.
- Performance status > 2 by ECOG criteria
- Patients who are unable to lie on their back and raise their arm above their head in the treatment planning position for radiotherapy
- Patients with a clinically unstable medical condition
- Patients with a life-threatening disease state
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- History or suspicion of serious life-threatening allergic reaction to Tc-99m imaging agents.
- Patients that have had breast-conservation surgery with positive margins or any patient with negative margins with a tumor positive for an extensive intraductal component.
- Patients that are not able to use the ABC device.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Health Systems
Ann Arbor, Michigan, 48109-5010
About this study
Radiotherapy has been shown to reduce breast-cancer specific mortality in patients at high risk for distant dissemination. It has also been shown to increase rates of non-breast cancer deaths and morbidity due to cardiovascular and pulmonary toxicity. Although treatment planning has improved significantly through the years, recent reports still demonstrate treatment-related morbidity even with 3-dimensional planned techniques. Thus, while 3D planning represents the state of the art treatment for loco-regional radiotherapy for breast cancer, further improvement is needed to continue to decrease heart and lung exposure. The ultimate goal of the proposed research is to determine whether treatment planning using intensity-modulated radiotherapy (IMRT), the "next generation" of radiation treatment delivery systems, results in less radiation exposure to the heart and lungs than the best current RT technique in women with node positive breast cancer. This proposal will test the potential clinical value of IMRT compared to the best standard 3D plan (partially wide tangent fields, PWTF) in the treatment of breast cancer. These two treatment techniques will be studied in a Phase II randomized trial using quantitative indicators of potential cardiac and lung toxicity. The preliminary data generated from this trial will be used to ultimately justify a multi-institutional comparison of the two treatment techniques with long-term clinical cardiac and pulmonary toxicity as endpoints.
Read the detailed description
- Primary Objective 1.1 To compare the extent of new myocardial perfusion defects following breast cancer radiotherapy using the best standard 3-D radiotherapy technique, partially wide tangent fields, versus the best optimized technique.
- Secondary Objectives 2.1 To compare changes in ejection fraction and alterations in cardiac wall motion with treatment by technique 2.2 To compare changes in lung perfusion defects and pulmonary function tests (DLCO, FEV1, and FVC) by technique 2.3 To compare rates of pericarditis and pneumonitis by technique
Cardiac Endpoints: Myocardial SPECT-CT perfusion defects, ejection fraction, alterations in cardiac wall motion, per SPECT-CT (adenosine stress and rest (if necessary)) scan.
Pulmonary Endpoints: Lung SPECT-CT perfusion defects per SPECT-CT scan, and changes in pulmonary function tests: DLCO, FEV1, FVC Clinical Endpoints: pericarditis and pneumonitis.
- Conditions
- Breast Cancer
- Being tested
- IMRT, 3D
- Keywords
- left sided
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMRTRadiation
All patients treated with the optimized plan will be treated to the entire target volume to 52.2 Gy in 1.74 Gy fractions, which is biologically equivalent to 50 Gy in 2 Gy fractions. This fractionation scheme will allow the boost of 10 Gy to be incorporated into the planning directive and to be delivered simultaneously with the treatment to the remaining target volume.
3DRadiation
All patients treated using the best standard technique will receive 50 Gy in 2 Gy fractions or 50.4 Gy in 1.8 Gy fractions to the entire target volume delivering one treatment per day, five fractions per week (excluding holidays). A boost of 10 Gy to the tumor bed of an intact breast will be delivered. Patients treated to the chest wall will receive a 10Gy scar boost if mastectomy margins are positive in a patient with Stage II disease or if the patient was originally diagnosed with T3 or T4 (Stage III) disease
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Best Delivery-optimized radiotherapy technique (IMRT) Receives: Radiation: IMRT |
| 2 | Active comparator | Best 3-dimensional standard PWTF technique Receives: Radiation: 3D |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Participants With a Significant Increase in Perfusion Defects (PD)
To compare the extent of new myocardial perfusion defects following breast cancer radiotherapy using the best standard 3-D radiotherapy technique, partially wide tangent fields, versus the best optimized technique. Perfusion defects (PD) were assessed by comparing normalized perfusion distributions against our institution's normal polar map databases for the left anterior descending artery (LAD) using thresholds of 2.5-SD (standard deviation) and 1.5-SD below the normal mean. On the basis of interest variability, a PD increase greater than 5% or 10% was considered significant for 2.5- and 1.5-SD thresholds, respectively.
Measured: 1 Year
Secondary outcomes (3)
Mean Percent Change in Ejection Fraction (LVEF)
To compare change in ejection fraction between treatment arms.
Measured: baseline to approx 1 year
Number of Participants With New Lung Perfusion Defects
To compare changes in lung perfusion defects by treatment arm. Perfusion defects (PD) were assessed by comparing normalized perfusion distributions against our institution's normal polar map databases for the left anterior descending artery (LAD).
Measured: baseline to approx 1 year
The Number of Participants That Experience Pericarditis and Pneumonitis
To compare rates of pericarditis and pneumonitis by treatment arm.
Pericarditis (inflammation of the pericardium):
Grade1: Asymptomatic, ECG or physical exam; changes consistent with pericarditis Grade 2: Symptomatic pericarditis Grade 3: Pericarditis with physiologic consequences Grade 4: Life-threatening Pneumonitis (inflammation of the walls of the alveoli in the lungs) Grade 1: Asymptomatic, radiographic findings only Grade 2: Symptomatic, not interfering with ADL (activities of daily living) Grade 3: Symptomatic, interfering with ADL Grade 4: Life-threatening
Measured: approx 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2007 (estimated)
- Study startApr 2006
- Primary completionApr 2015
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lori Pierce, MD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00581256
- Sponsor's protocol ID
- UMCC 2004.038
- Other IDs
- IRB #2002-387 ~ HUM 39607
- Status last verified
- Sep 2017
- First submitted
- 20 Dec 2007
- Last updated
- 31 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Jagsi R, Griffith KA, Moran JM, Ficaro E, Marsh R, Dess RT, Chung E, Liss AL, Hayman JA, Mayo CS, Flaherty K, Corbett J, Pierce L. A Randomized Comparison of Radiation Therapy Techniques in the Management of Node-Positive Breast Cancer: Primary Outcomes Analysis. Int J Radiat Oncol Biol Phys. 2018 Aug 1;101(5):1149-1158. doi: 10.1016/j.ijrobp.2018.04.075. Epub 2018 May 5.
PubMed 30012527
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Comparison of Radiation Therapy Techniques in the Management of Node Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT00581256
- Acronym / sponsor ID
- UMCC 2004.038
- Conditions
- Breast Cancer
- Keywords
- left sided
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Apr 2006
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 27 Dec 2007 (estimated)
- Results
- Posted 1 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Radiotherapy has been shown to reduce breast-cancer specific mortality in patients at high risk for distant dissemination. It has also been shown to increase rates of non-breast cancer deaths and morbidity due to cardiovascular and pulmonary toxicity. Although treatment planning has improved significantly through the years, recent reports still demonstrate treatment-related morbidity even with 3-dimensional planned techniques. Thus, while 3D planning represents the state of the art treatment for loco-regional radiotherapy for breast cancer, further improvement is needed to continue to decrease heart and lung exposure. The ultimate goal of the proposed research is to determine whether treatment planning using intensity-modulated radiotherapy (IMRT), the "next generation" of radiation treatment delivery systems, results in less radiation exposure to the heart and lungs than the best current RT technique in women with node positive breast cancer. This proposal will test the potential clinical value of IMRT compared to the best standard 3D plan (partially wide tangent fields, PWTF) in the treatment of breast cancer. These two treatment techniques will be studied in a Phase II randomized trial using quantitative indicators of potential cardiac and lung toxicity. The preliminary data generated from this trial will be used to ultimately justify a multi-institutional comparison of the two treatment techniques with long-term clinical cardiac and pulmonary toxicity as endpoints.
Detailed description
- Primary Objective 1.1 To compare the extent of new myocardial perfusion defects following breast cancer radiotherapy using the best standard 3-D radiotherapy technique, partially wide tangent fields, versus the best optimized technique.
- Secondary Objectives 2.1 To compare changes in ejection fraction and alterations in cardiac wall motion with treatment by technique 2.2 To compare changes in lung perfusion defects and pulmonary function tests (DLCO, FEV1, and FVC) by technique 2.3 To compare rates of pericarditis and pneumonitis by technique
Cardiac Endpoints: Myocardial SPECT-CT perfusion defects, ejection fraction, alterations in cardiac wall motion, per SPECT-CT (adenosine stress and rest (if necessary)) scan.
Pulmonary Endpoints: Lung SPECT-CT perfusion defects per SPECT-CT scan, and changes in pulmonary function tests: DLCO, FEV1, FVC Clinical Endpoints: pericarditis and pneumonitis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Radiation: IMRTBest Delivery-optimized radiotherapy technique (IMRT) |
| 2 | Active comparator | Radiation: 3DBest 3-dimensional standard PWTF technique |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Eligibility Criteria
- Breast cancer diagnosis: Patients must have histologically confirmed adenocarcinoma of the breast requiring comprehensive loco-regional irradiation that includes treatment to the intact breast/chest wall, supraclavicular (SCV), infraclavicular nodes (ICV), and internal mammary nodes (IMN).
- Patients must have pathologic T 1, 2, 3 or 4, N 1, 2, or 3 Stage II or III disease as defined by the AJCC Staging System, 6th edition. Patients who do not undergo axillary staging but are at risk for nodal involvement may also be treated.
- All patients must have left-sided breast cancer.
- Both men and women are eligible.
Key exclusion criteria (9 listed)
- Patients who are pregnant or are nursing are excluded.
- Pathologically node negative breast cancer unless treated with neo-adjuvant chemotherapy.
- Performance status > 2 by ECOG criteria
- Patients who are unable to lie on their back and raise their arm above their head in the treatment planning position for radiotherapy
- Patients with a clinically unstable medical condition
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IMRTAll patients treated with the optimized plan will be treated to the entire target volume to 52.2 Gy in 1.74 Gy fractions, which is biologically equivalent to 50 Gy in 2 Gy fractions. This fractionation scheme will allow the boost of 10 Gy to be incorporated into the planning directive and to be delivered simultaneously with the treatment to the remaining target volume. | Radiation | 1 |
| 3DAll patients treated using the best standard technique will receive 50 Gy in 2 Gy fractions or 50.4 Gy in 1.8 Gy fractions to the entire target volume delivering one treatment per day, five fractions per week (excluding holidays). A boost of 10 Gy to the tumor bed of an intact breast will be delivered. Patients treated to the chest wall will receive a 10Gy scar boost if mastectomy margins are positive in a patient with Stage II disease or if the patient was originally diagnosed with T3 or T4 (Stage III) disease | Radiation | 2 |
Primary outcome
The Number of Participants With a Significant Increase in Perfusion Defects (PD)
Time frame: 1 Year
To compare the extent of new myocardial perfusion defects following breast cancer radiotherapy using the best standard 3-D radiotherapy technique, partially wide tangent fields, versus the best optimized technique. Perfusion defects (PD) were assessed by comparing normalized perfusion distributions against our institution's normal polar map databases for the left anterior descending artery (LAD) using thresholds of 2.5-SD (standard deviation) and 1.5-SD below the normal mean. On the basis of interest variability, a PD increase greater than 5% or 10% was considered significant for 2.5- and 1.5-SD thresholds, respectively.
3 secondary outcomes
Mean Percent Change in Ejection Fraction (LVEF)
Time frame: baseline to approx 1 year
Number of Participants With New Lung Perfusion Defects
Time frame: baseline to approx 1 year
The Number of Participants That Experience Pericarditis and Pneumonitis
Time frame: approx 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30012527Jagsi R, Griffith KA, Moran JM, Ficaro E, Marsh R, Dess RT, Chung E, Liss AL, Hayman JA, Mayo CS, Flaherty K, Corbett J, Pierce L. A Randomized Comparison of Radiation Therapy Techniques in the Management of Node-Positive Breast Cancer: Primary Outcomes Analysis. Int J Radiat Oncol Biol Phys. 2018 Aug 1;101(5):1149-1158. doi: 10.1016/j.ijrobp.2018.04.075. Epub 2018 May 5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lori Pierce, MD principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IMRT and 3D in people with Breast Cancer, run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Number of Participants With a Significant Increase in Perfusion Defects (PD) (time frame: 1 Year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00581256, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2017.