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Hypofractionated Partial Breast Irradiation in Treating Patients With Early Stage Breast Cancer

Primary Purpose

Ductal Breast Carcinoma In Situ, Early-Stage Breast Carcinoma, Invasive Breast Carcinoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Partial Breast Irradiation
Questionnaire Administration
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ductal Breast Carcinoma In Situ

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of pathologically-confirmed invasive breast cancer or ductal carcinoma in situ
  • Pathologic T stage of Tis, T1, or T2 with total size of tumor =< 3 cm (this size criteria applies to both pure DCIS and invasive tumors)
  • For patients with invasive breast cancer, pathologic N stage of N0, N0 (i-), or N0 (i+); pathologic staging of the axilla is not required for patients with pure DCIS
  • Treatment with breast conserving surgery
  • Unifocal primary tumor based on imaging and clinical assessment; microscopic multifocality is allowed
  • Final surgical margins negative defined as no tumor on ink; lobular carcinoma in situ involving the final surgical margin will be disregarded
  • For invasive cancers, the tumor must be estrogen receptor positive (defined as 10% or greater expression of estrogen receptor)
  • If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed at least one month prior to study registration and the patient must have no evidence of disease for this prior non-breast cancer
  • Patients must be enrolled on the trial within 12 weeks of the later of two dates: the final breast conserving surgical procedure or administration of the last cycle of cytotoxic chemotherapy
  • Final criteria for eligibility established after simulation: The tumor bed can be readily visualized on simulation computed tomography (CT) and is localized to one quadrant or region of the breast that is amenable to partial breast irradiation

Exclusion Criteria:

  • Tumor invasion of the skin including dermis, chest wall, or pectoralis musculature
  • Any evidence of nodal positivity beyond pathologic stage of pN0(i+)
  • Systemic chemotherapy prior to final breast conserving surgery
  • Patient is pregnant or nursing
  • History of therapeutic irradiation to the breast, lower neck, mediastinum or other area in which there could potentially be overlap with the affected breast
  • History of prior invasive or in situ cancer in either breast
  • Current diagnosis of bilateral breast cancer
  • History of lupus or scleroderma

Sites / Locations

  • Baptist MD Anderson Cancer Center
  • Piedmont Hospital
  • Community Cancer Center East
  • Covenant Medical Center Harrison
  • Summit Medical Group
  • Cooper Hospital University Medical Center
  • MD Anderson Cancer Center at Cooper-Voorhees
  • Presbyterian Hospital
  • OhioHealth Mansfield Hospital
  • MD Anderson in The Woodlands
  • M D Anderson Cancer Center
  • MD Anderson West Houston
  • MD Anderson League City
  • Saint Luke's Baptist Health System
  • MD Anderson in Sugar Land

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (hypofractionated partial breast irradiation)

Arm II (hypofractionated partial breast irradiation)

Arm Description

Patients undergo hypofractionated partial breast irradiation daily for 5 days. Patients may then receive 3 additional boost fractions at the discretion of the doctor.

Patients undergo standard breast irradiation daily for 15 days. Patients may then receive 5 additional boost fractions at the discretion of the doctor.

Outcomes

Primary Outcome Measures

Risk of grade 2 or higher toxicity
Will evaluate whether or not the risk of this outcome is higher than the risk of grade 2+ toxic events in the best performing arm of our prior clinical trial that evaluated dosing schedules of whole breast irradiation (2010-0559).

Secondary Outcome Measures

Patient-reported cosmetic outcome
Patient-reported cosmetic outcome, functional status, and breast pain will be measured using the Breast Cancer Treatment Outcomes Scale (BCTOS) and will be compared for the IMPORT Low versus OPAL regimens. Each outcome will be evaluated both as a continuous variable and as a dichotomous variable with a cutpoint of >= 2.5, indicating a moderate or greater average change in the treated breast compared to the untreated breast which serves as an internal control. Will use descriptive statistics to summarize patient-reported cosmetic outcome, functional status, and breast pain over time. Box plots and graphical measures will be used to display the distribution of these outcomes over time and by treatment arm. Will conduct linear mixed models to assess changes in patient-reported cosmetic outcome, functional status, and breast pain scores over time. A random intercept will be included to account for within-subject correlations.
Physician-reported and photographically-assessed cosmetic outcome
Physician-reported cosmetic outcome, functional status, and breast pain will be measured using the Breast Cancer Treatment Outcomes Scale (BCTOS) and will be compared for the IMPORT Low versus OPAL regimens. Each outcome will be evaluated both as a continuous variable and as a dichotomous variable with a cutpoint of >= 2.5, indicating a moderate or greater average change in the treated breast compared to the untreated breast which serves as an internal control. Will use descriptive statistics to summarize patient-reported cosmetic outcome, functional status, and breast pain over time. Box plots and graphical measures will be used to display the distribution of these outcomes over time and by treatment arm. Will conduct linear mixed models to assess changes in patient-reported cosmetic outcome, functional status, and breast pain scores over time. A random intercept will be included to account for within-subject correlations.
Risk of pathologically-confirmed invasive and/or ipsilateral breast tumor recurrence (IBTR)
Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. IBTR will be measured from the date of treatment initiation to the date of last evaluation or IBTR. The 5-year risk of IBTR and any recurrence will be estimated along with 95% confidence intervals. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.
Risk of any recurrence of breast cancer
Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. Recurrence-free survival will be measured from the date of radiation treatment initiation to the earliest date of last clinic visit, date of first recurrence, or date of death. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.
Disease free survival (DFS)
Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. DFS will be measured from date of treatment initiation to the earliest date of last clinic visit, date of progression, date of recurrence, date of metastasis, or date of death. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.
Overall survival
Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. OS will be measured from the date of treatment initiation to the earliest date of last contact or death. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.
Incidence of adverse events
Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4. Differences in National Cancer Institute CTCAE and Subjective, Objective, Management, Analytic (SOMA) toxicity by treatment arm will be evaluated using chi-square test or Fisher's exact test, as appropriate.
Feasibility of conducting multi-center radiation therapy trials within the MD Anderson Network
The trial will be considered feasible if >= 90% of enrolled and treated patients receive the prescribed radiation dosing per protocol without deviations.
TGF-beta analysis
For this analysis, the primary outcome is grade 2 or higher breast fibrosis measured using the Subjective, Objective, Management, Analytic/Late Effects Normal Tissue Task Force scale at the 3.5 year follow up visit. The exposure of interest is the presence of at least one copy of the C-509T allele in germline deoxyribonucleic acid (DNA). Will also conduct exploratory analyses to assess the association of TGF-beta genotype with cosmetic outcome, other PROs, and toxicities. T-test or rank-sum test will be used for continuous measures and chi-squared or Fishers exact test will be used for categorical measures.

Full Information

First Posted
March 6, 2017
Last Updated
July 18, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03077841
Brief Title
Hypofractionated Partial Breast Irradiation in Treating Patients With Early Stage Breast Cancer
Official Title
Optimizing Preventative Adjuvant Linac-Based Radiation: The OPAL Trial a Phase II/III Study of Hypofractionated Partial Breast Irradiation in Women With Early Stage Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 6, 2017 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
August 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies how well hypofractionated partial breast irradiation works in treating patients with early stage breast cancer. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Treating only the part of the breast where the cancer started may lead to fewer side effects than standard treatment.
Detailed Description
PRIMARY OBJECTIVE: I. The risk of grade 2 or higher toxicity occurring during radiation and through the 6 month post-radiation follow up visit in patients treated with Optimizing Preventative Adjuvant Linac-based Radiation (OPAL) regimen. SECONDARY OBJECTIVES: I. To measure patient-reported cosmetic outcome, functional status, and breast pain with the OPAL regimen at 6 months, one year, two years, three years, four years, and five years after completing the OPAL regimen. II. To measure physician-reported and photographically-assessed cosmetic outcome at 6 months, one year, two years, three years, four years, and five years after completing the OPAL regimen and to compare this to the best performing arm of 2010-0559. III. To determine the 5-year risk of pathologically-confirmed invasive and/or in situ ipsilateral breast tumor recurrence (IBTR) for patients with ductal breast carcinoma in situ (DCIS) and early invasive breast cancer. IV. To determine the 5-year risk of any recurrence of breast cancer, disease-free survival, and overall survival. V. To determine maximal late (within 5 years) toxicities using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0 scale. VI. To establish the feasibility of conducting multi-center radiation therapy trials within the MD Anderson Network. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo hypofractionated partial breast irradiation daily for 5 days. Patients may then receive 3 additional boost fractions at the discretion of the doctor. ARM II: Patients undergo standard breast irradiation daily for 15 days. Patients may then receive 5 additional boost fractions at the discretion of the doctor. After completion of study treatment, patients are followed up at 6 months, and at 1.5, 3.5, and 5.5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ductal Breast Carcinoma In Situ, Early-Stage Breast Carcinoma, Invasive Breast Carcinoma, Stage 0 Breast Cancer AJCC v6 and v7, Stage I Breast Cancer AJCC v7, Stage IA Breast Cancer AJCC v7, Stage IB Breast Cancer AJCC v7, Stage II Breast Cancer AJCC v6 and v7, Stage IIA Breast Cancer AJCC v6 and v7, Stage IIB Breast Cancer AJCC v6 and v7

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
928 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I (hypofractionated partial breast irradiation)
Arm Type
Experimental
Arm Description
Patients undergo hypofractionated partial breast irradiation daily for 5 days. Patients may then receive 3 additional boost fractions at the discretion of the doctor.
Arm Title
Arm II (hypofractionated partial breast irradiation)
Arm Type
Active Comparator
Arm Description
Patients undergo standard breast irradiation daily for 15 days. Patients may then receive 5 additional boost fractions at the discretion of the doctor.
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Radiation
Intervention Name(s)
Partial Breast Irradiation
Intervention Description
Undergo hypofractionated partial breast irradiation
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Risk of grade 2 or higher toxicity
Description
Will evaluate whether or not the risk of this outcome is higher than the risk of grade 2+ toxic events in the best performing arm of our prior clinical trial that evaluated dosing schedules of whole breast irradiation (2010-0559).
Time Frame
At 6 months post radiation
Secondary Outcome Measure Information:
Title
Patient-reported cosmetic outcome
Description
Patient-reported cosmetic outcome, functional status, and breast pain will be measured using the Breast Cancer Treatment Outcomes Scale (BCTOS) and will be compared for the IMPORT Low versus OPAL regimens. Each outcome will be evaluated both as a continuous variable and as a dichotomous variable with a cutpoint of >= 2.5, indicating a moderate or greater average change in the treated breast compared to the untreated breast which serves as an internal control. Will use descriptive statistics to summarize patient-reported cosmetic outcome, functional status, and breast pain over time. Box plots and graphical measures will be used to display the distribution of these outcomes over time and by treatment arm. Will conduct linear mixed models to assess changes in patient-reported cosmetic outcome, functional status, and breast pain scores over time. A random intercept will be included to account for within-subject correlations.
Time Frame
At 6 months, one year, two years, three years, four years, and five years after completing the optimizing preventative adjuvant linac-based radiation (OPAL) regimen
Title
Physician-reported and photographically-assessed cosmetic outcome
Description
Physician-reported cosmetic outcome, functional status, and breast pain will be measured using the Breast Cancer Treatment Outcomes Scale (BCTOS) and will be compared for the IMPORT Low versus OPAL regimens. Each outcome will be evaluated both as a continuous variable and as a dichotomous variable with a cutpoint of >= 2.5, indicating a moderate or greater average change in the treated breast compared to the untreated breast which serves as an internal control. Will use descriptive statistics to summarize patient-reported cosmetic outcome, functional status, and breast pain over time. Box plots and graphical measures will be used to display the distribution of these outcomes over time and by treatment arm. Will conduct linear mixed models to assess changes in patient-reported cosmetic outcome, functional status, and breast pain scores over time. A random intercept will be included to account for within-subject correlations.
Time Frame
At 6 months, one year, two years, three years, four years, and five years after completing the OPAL regimen
Title
Risk of pathologically-confirmed invasive and/or ipsilateral breast tumor recurrence (IBTR)
Description
Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. IBTR will be measured from the date of treatment initiation to the date of last evaluation or IBTR. The 5-year risk of IBTR and any recurrence will be estimated along with 95% confidence intervals. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.
Time Frame
At 5 years
Title
Risk of any recurrence of breast cancer
Description
Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. Recurrence-free survival will be measured from the date of radiation treatment initiation to the earliest date of last clinic visit, date of first recurrence, or date of death. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.
Time Frame
At 5 years
Title
Disease free survival (DFS)
Description
Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. DFS will be measured from date of treatment initiation to the earliest date of last clinic visit, date of progression, date of recurrence, date of metastasis, or date of death. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.
Time Frame
At 5 years
Title
Overall survival
Description
Will be estimated using Kaplan and Meier product-limit estimator and modeled with Cox proportional hazards regression. OS will be measured from the date of treatment initiation to the earliest date of last contact or death. Differences in each of these outcomes by treatment arm will be assessed using the log-rank test. Cox proportional hazards regression and/or competing risks regression will be used if needed to account for imbalance among treatment arms with respect to risk factors for these outcomes.
Time Frame
At 5 years
Title
Incidence of adverse events
Description
Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4. Differences in National Cancer Institute CTCAE and Subjective, Objective, Management, Analytic (SOMA) toxicity by treatment arm will be evaluated using chi-square test or Fisher's exact test, as appropriate.
Time Frame
Up to 5 years
Title
Feasibility of conducting multi-center radiation therapy trials within the MD Anderson Network
Description
The trial will be considered feasible if >= 90% of enrolled and treated patients receive the prescribed radiation dosing per protocol without deviations.
Time Frame
5 years
Title
TGF-beta analysis
Description
For this analysis, the primary outcome is grade 2 or higher breast fibrosis measured using the Subjective, Objective, Management, Analytic/Late Effects Normal Tissue Task Force scale at the 3.5 year follow up visit. The exposure of interest is the presence of at least one copy of the C-509T allele in germline deoxyribonucleic acid (DNA). Will also conduct exploratory analyses to assess the association of TGF-beta genotype with cosmetic outcome, other PROs, and toxicities. T-test or rank-sum test will be used for continuous measures and chi-squared or Fishers exact test will be used for categorical measures.
Time Frame
Up to 5 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of pathologically-confirmed invasive breast cancer or ductal carcinoma in situ Pathologic T stage of Tis, T1, or T2 with total size of tumor =< 3 cm (this size criteria applies to both pure DCIS and invasive tumors) For patients with invasive breast cancer, pathologic N stage of N0, N0 (i-), or N0 (i+); pathologic staging of the axilla is not required for patients with pure DCIS Treatment with breast conserving surgery Unifocal primary tumor based on imaging and clinical assessment; microscopic multifocality is allowed Final surgical margins negative defined as no tumor on ink; lobular carcinoma in situ involving the final surgical margin will be disregarded For invasive cancers, the tumor must be estrogen receptor positive (defined as 10% or greater expression of estrogen receptor) If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed at least one month prior to study registration and the patient must have no evidence of disease for this prior non-breast cancer Patients must be enrolled on the trial within 12 weeks of the later of two dates: the final breast conserving surgical procedure or administration of the last cycle of cytotoxic chemotherapy Final criteria for eligibility established after simulation: The tumor bed can be readily visualized on simulation computed tomography (CT) and is localized to one quadrant or region of the breast that is amenable to partial breast irradiation Exclusion Criteria: Tumor invasion of the skin including dermis, chest wall, or pectoralis musculature Any evidence of nodal positivity beyond pathologic stage of pN0(i+) Systemic chemotherapy prior to final breast conserving surgery Patient is pregnant or nursing History of therapeutic irradiation to the breast, lower neck, mediastinum or other area in which there could potentially be overlap with the affected breast History of prior invasive or in situ cancer in either breast Current diagnosis of bilateral breast cancer History of lupus or scleroderma
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin D Smith
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Baptist MD Anderson Cancer Center
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Piedmont Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Community Cancer Center East
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46219
Country
United States
Facility Name
Covenant Medical Center Harrison
City
Saginaw
State/Province
Michigan
ZIP/Postal Code
48602
Country
United States
Facility Name
Summit Medical Group
City
Berkeley Heights
State/Province
New Jersey
ZIP/Postal Code
07922
Country
United States
Facility Name
Cooper Hospital University Medical Center
City
Camden
State/Province
New Jersey
ZIP/Postal Code
08103
Country
United States
Facility Name
MD Anderson Cancer Center at Cooper-Voorhees
City
Voorhees
State/Province
New Jersey
ZIP/Postal Code
08043
Country
United States
Facility Name
Presbyterian Hospital
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
OhioHealth Mansfield Hospital
City
Mansfield
State/Province
Ohio
ZIP/Postal Code
44903
Country
United States
Facility Name
MD Anderson in The Woodlands
City
Conroe
State/Province
Texas
ZIP/Postal Code
77384
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
MD Anderson West Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77079
Country
United States
Facility Name
MD Anderson League City
City
League City
State/Province
Texas
ZIP/Postal Code
77573
Country
United States
Facility Name
Saint Luke's Baptist Health System
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
MD Anderson in Sugar Land
City
Sugar Land
State/Province
Texas
ZIP/Postal Code
77478
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdsnderson.org
Description
MD AnDERSON CANCRER CENTER WEBSITE

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Hypofractionated Partial Breast Irradiation in Treating Patients With Early Stage Breast Cancer

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