Breast Cancer
Conditions
Brief summary
This protocol is for patients with newly diagnosed breast cancer with an indication for post-operative radiotherapy after neo-adjuvant chemotherapy and surgery.
Detailed description
Protocol has two cohorts. Cohort 1 will receive radiation to breast and chest wall. Prone whole breast or chest wall 3D-CRT or IMRT at 2.7 Gy x 15 fractions (40.50 Gy) with a concomitant boost of 0.50 (7.5 Gy) to the original tumor bed in post-segmental mastectomy patients or mastectomy scar in post-mastectomy patients. Patients who have undergone reconstruction will not receive concomitant boost. Cohort 2 patients will receive radiation to breast, chest wall and LevelII/SCV nodes. In addition to receiving radiation to the original tumor bed, patients will also receive radiation to Level III axillary nodes and Supraclavicular nodes: 3D-CRT or IMRT at 2.7 Gy X 15 fraction (40.50 Gy). Patients will complete treatment in three weeks (15 fractions). All patients will be followed at 3 months after the completion of treatment then yearly for the next 5 years.
Interventions
RADIATIONRadiation
(Post-segmental Mastectomy, post-mastectomy and Post-mastectomy with expanders or final reconstruction): Prone whole breast or chest wall 3D-CRT or IMRT at 2.7 Gy X 15 fractions (40.50 Gy) with a concomitant boost of 0.50 Gy (7.5 Gy) to the original tumor bed in post-segmental mastectomy patients or mastectomy scar in post-mastectomy patients. Patients who have undergone reconstruction will not receive concomitant boost.
Sponsors
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
19 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
The study will also include patients who because of COVID had undergone up to 3 months neoadjuvant hormonal therapy before surgery for clinical T1/T2 BC. Inclusion Criteria: * Age older than 18 * Pre- or post-menopausal women with Stage I-III breast cancer * Status post neoadjuvant systemic therapy * Status post-chemotherapy breast surgery * Original biopsy-proven invasive breast cancer, excised with negative margins of at least 1 mm (patients with focally positive margin are not excluded). * Status post segmental mastectomy or mastectomy, with either negative sentinel node biopsy and/or axillary node dissection (at least 6 nodes removed). * Patient needs to be able to understand and demonstrate willingness to sign a written informed consent document
Exclusion criteria
* Previous radiation therapy to the ipsilateral breast and/or nodal area * Active connective tissue disorders, such as lupus or scleroderma requiring flare therapy * Pregnant or lactating women * Concurrent chemotherapy, with the exception of anti HER2neu therapies * Inadequate axillary dissection in a setting of positive sentinel node * Patients with more than 5 nodes involved at axillary dissection will be excluded from this study since they will be eligible to receive radiotherapy to level I and II axilla.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute Toxicity Will be Measured by Evaluating the Number of Patients Who Experience Grade II-III Dermatitis Within 60 Days of Radiation Therapy. | 60 days from start of radiation therapy. | feasibility of accelerated radiotherapy in the post-operative setting of breast cancer patients treated by neo-adjuvant chemotherapy and surgery will be measured, by evaluating the number of patients who experience grade II-III dermatitis within 60 days of the end of treatment. Acute Toxicity will be graded using CTCAE v4.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life of Patients. | Baseline, end of radiation, 1 month post radiation. | The patient reported outcomes or quality of life questionnaires are assessed for the aesthetic and functional outcomes after breast radiation therapy. The score value ranges from 1.00 - 4.00, with a higher score reflecting a poorer outcome. Following is the criteria for evaluating breast radiation therapy outcomes in patients: good (1.00-1.75) ; intermediate (1.76-2.50), fair (2.51 -3.25) and poor (3.26 - 4.00). |
| Late Radiation Toxicity in Treated Patients | 2 years and 5 years | incidence of late radiation toxicity (brachial plexopathy, fibrosis and telangiectasia) will be evaluated and genetic determinants of breast fibrosis will be identified. |
| Number of Patients With Grades 2 or Higher Toxicity | 2 years and 5 years | Number of patients with grades 2 or higher toxicity |
| Quality of Life of Patients | 2 years | The patient reported outcomes or quality of life questionnaires are assessed for the aesthetic and functional outcomes after breast radiation therapy. The score value ranges from 1.00 - 4.00, with a higher score reflecting a poorer outcome. Following is the criteria for evaluating breast radiation therapy outcomes in patients: good (1.00-1.75) ; intermediate (1.76-2.50), fair (2.51 -3.25) and poor (3.26 - 4.00). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSilvia Formenti, M.D.
Weill Cornell Medicine - New York Presbyterian Hospital
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (Post-segmental Mastectomy, post-mastectomy and Post-mastectomy with expanders or final reconstruction): Prone whole breast or chest wall 3D-CRT or IMRT at 2.7 Gy X 15 fractions (40.50 Gy) with a concomitant boost of 0.50 Gy (7.5 Gy) to the original tumor bed in post-segmental mastectomy patients or mastectomy scar in post-mastectomy patients. Patients who have undergone reconstruction will not receive concomitant boost.
Radiation therapy : Prone whole breast or chest wall 3D-CRT or IMRT at 2.7 Gy X 15 fractions (40.50 Gy) with a concomitant boost of 0.50 Gy (7.5 Gy) to the original tumor bed in post-segmental mastectomy patients or mastectomy scar in post-mastectomy patients. Patients who have undergone reconstruction will not receive concomitant boost.
Radiation: (Post-segmental Mastectomy, post-mastectomy and Post-mastectomy with expanders or final reconstruction):
Prone whole breast or chest wall 3D-CRT or IMRT at 2.7 Gy X 15 fractions (40.50 Gy) with a concomitant boost of 0.50 Gy (7.5 Gy) to the original tumor bed in post-segmental mastectomy patients or mastectomy scar in post-mastectomy patients. Patients who have undergone reconstruction will not receive concomitant boost. | 47 |
| Cohort 2 In addition to receiving radiation to the original tumor bed, patients will also receive radiation to Level III axillary nodes and Supraclavicular nodes: 3D-CRT or IMRT at 2.7 Gy X 15 fraction (40.50 Gy)
Radiation Therapy : Prone whole breast or chest wall 3D-CRT or IMRT at 2.7 Gy X 15 fractions (40.50 Gy) with a concomitant boost of 0.50 Gy (7.5 Gy) to the original tumor bed in post-segmental mastectomy patients or mastectomy scar in post-mastectomy patients. Patients who have undergone reconstruction will not receive concomitant boost.
Radiation: (Post-segmental Mastectomy, post-mastectomy and Post-mastectomy with expanders or final reconstruction):
Prone whole breast or chest wall 3D-CRT or IMRT at 2.7 Gy X 15 fractions (40.50 Gy) with a concomitant boost of 0.50 Gy (7.5 Gy) to the original tumor bed in post-segmental mastectomy patients or mastectomy scar in post-mastectomy patients. Patients who have undergone reconstruction will not receive concomitant boost. | 41 |
| Total | 88 |
Baseline characteristics
| Characteristic | Total | Cohort 1 | Cohort 2 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 26 Participants | 18 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 62 Participants | 29 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants | 39 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 23 Participants | 12 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 36 Participants | 23 Participants | 13 Participants |
| Region of Enrollment United States | 88 participants | 47 participants | 41 participants |
| Sex: Female, Male Female | 88 Participants | 47 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 47 / 47 | 41 / 41 |
| other Total, other adverse events | 45 / 47 | 41 / 41 |
| serious Total, serious adverse events | 2 / 47 | 0 / 41 |
Outcome results
Primary
Acute Toxicity Will be Measured by Evaluating the Number of Patients Who Experience Grade II-III Dermatitis Within 60 Days of Radiation Therapy.
feasibility of accelerated radiotherapy in the post-operative setting of breast cancer patients treated by neo-adjuvant chemotherapy and surgery will be measured, by evaluating the number of patients who experience grade II-III dermatitis within 60 days of the end of treatment. Acute Toxicity will be graded using CTCAE v4.0.
Time frame: 60 days from start of radiation therapy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Acute Toxicity Will be Measured by Evaluating the Number of Patients Who Experience Grade II-III Dermatitis Within 60 Days of Radiation Therapy. | 0 Participants |
| Cohort 2 | Acute Toxicity Will be Measured by Evaluating the Number of Patients Who Experience Grade II-III Dermatitis Within 60 Days of Radiation Therapy. | 0 Participants |
Secondary
Change in Quality of Life of Patients.
The patient reported outcomes or quality of life questionnaires are assessed for the aesthetic and functional outcomes after breast radiation therapy. The score value ranges from 1.00 - 4.00, with a higher score reflecting a poorer outcome. Following is the criteria for evaluating breast radiation therapy outcomes in patients: good (1.00-1.75) ; intermediate (1.76-2.50), fair (2.51 -3.25) and poor (3.26 - 4.00).
Time frame: Baseline, end of radiation, 1 month post radiation.
Population: Data in the table is representative of those participants who completed the questionnaires.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Change in Quality of Life of Patients. | End of Radiation | 1.80 score on a scale | Standard Deviation 0.876 |
| Cohort 1 | Change in Quality of Life of Patients. | 1 month post radiation | 1.59 score on a scale | Standard Deviation 0.73 |
| Cohort 1 | Change in Quality of Life of Patients. | Baseline | 1.62 score on a scale | Standard Deviation 0.73 |
| Cohort 2 | Change in Quality of Life of Patients. | Baseline | 1.92 score on a scale | Standard Deviation 0.979 |
| Cohort 2 | Change in Quality of Life of Patients. | End of Radiation | 1.82 score on a scale | Standard Deviation 0.855 |
| Cohort 2 | Change in Quality of Life of Patients. | 1 month post radiation | 1.79 score on a scale | Standard Deviation 0.812 |
Secondary
Late Radiation Toxicity in Treated Patients
incidence of late radiation toxicity (brachial plexopathy, fibrosis and telangiectasia) will be evaluated and genetic determinants of breast fibrosis will be identified.
Time frame: 2 years and 5 years
Secondary
Number of Patients With Grades 2 or Higher Toxicity
Number of patients with grades 2 or higher toxicity
Time frame: 2 years and 5 years
Secondary
Quality of Life of Patients
The patient reported outcomes or quality of life questionnaires are assessed for the aesthetic and functional outcomes after breast radiation therapy. The score value ranges from 1.00 - 4.00, with a higher score reflecting a poorer outcome. Following is the criteria for evaluating breast radiation therapy outcomes in patients: good (1.00-1.75) ; intermediate (1.76-2.50), fair (2.51 -3.25) and poor (3.26 - 4.00).
Time frame: 2 years
Other Pre-specified
Distant Recurrences Will be Measured.
Time frame: up to 10 years
Other Pre-specified
Local Control Rates Will be Measured.
Time frame: up to 10 years
Other Pre-specified
Molecular Signatures That Predict Fibrosis Will be Prospectively Measured From Blood Samples.
The purpose of this portion of the study will be to collect blood from each subject accrued to the study and willing to donate a specimen of blood for research, to study the TGF-β1 polymorphisms that have been reported to be correlated with the development of fibrosis following radiotherapy for treatment of breast cancer.
Time frame: 10 years
Other Pre-specified
Overall Survival Will be Measured
Time frame: up to 10 years