Radiation Therapy in Treating Women With Locally Recurrent Breast Cancer Previously Treated With Repeat Breast-Preserving Surgery
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|ClinicalTrials.gov Identifier: NCT01082211|
Recruitment Status : Active, not recruiting
First Posted : March 8, 2010
Results First Posted : June 8, 2017
Last Update Posted : June 18, 2018
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery kill any remaining tumor cells and may be an effective treatment for breast cancer.
PURPOSE: This phase II trial is studying how well radiation therapy works in treating women with locally recurrent breast cancer previously treated with repeat breast-conserving surgery.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Radiation: 3D-Conformal External Beam||Phase 2|
- To evaluate skin, breast, and chest wall adverse events occurring within 1 year after completion of 3D-conformal partial-breast re-irradiation following repeat breast-preserving surgery in patients with locally recurrent breast carcinoma.
- To evaluate the adverse events occurring after 1 year from the completion of re-irradiation and at any time.
- To evaluate in-breast control rate in patients treated with this regimen.
- To evaluate freedom-from-mastectomy rate in these patients.
- To evaluate the rate of circulating tumor cells (CTCs) in this patient population and to document eradication of CTCs by locoregional therapy.
- To determine whether translational objective will correlate with eradication or presence of CTCs with in-breast recurrence and distant metastasis-free survival.
- To evaluate cosmesis as judged by the patient and independent evaluation.
- To evaluate distant metastasis-free survival, mastectomy-free survival, and overall survival of patients treated with this regimen.
OUTLINE: This is a multicenter study.
Patients undergo 3-dimensional conformal accelerated partial-breast irradiation twice daily, 5 days a week, for 3 weeks.
Some patients undergo blood sample collection at baseline and within 3 weeks after completion of radiotherapy for circulating tumor cells analysis.
Some patients complete questionnaires on cosmesis at baseline and at 1 and 3 years following radiotherapy.
After completion of study therapy, patients are followed up periodically for 4-5 years and then every year thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||65 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Repeat Breast Preserving Surgery and 3D-Conformal Partial Breast Re-Irradiation (PBrI) for Local Recurrence of Breast Carcinoma|
|Study Start Date :||June 2010|
|Actual Primary Completion Date :||November 2014|
|Estimated Study Completion Date :||November 2020|
Experimental: Partial Breast Re-Irradiation
Partial Breast Re-Irradiation (PBrI) 3D-Conformal External Beam 1.5 Gy x 15 (BID) to 45 Gy Total
Radiation: 3D-Conformal External Beam
Radiation was to be delivered in 2 fractions per day, each of 1.5 Gy, separated by at least six hours, given in 15 consecutive working days to a total of 30 fractions and 45 Gy. Radiation was to be prescribed to the treatment unit isocenter, positioned at the approximate center of the planning target volume.
- Number of Participants With Grade 3+ Treatment-related Skin, Fibrosis, and Breast Pain Adverse Events [ Time Frame: From the end of radiation to 1 year. ]Adverse events (AEs) were graded with Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade refers to the severity of the AE. The Common Terminology Criteria for Adverse Events (CTCAE) v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Based on a rate of 4% for the AEs of interest, a rate of ≥ 13% for these AEs with re-irradiation would be unacceptable. A sample size of 55 evaluable pts (eligible & started protocol treatment) would provide: 86% power to conclude an unacceptable rate of the specified AEs, if the true AE rate was at least 13%; 93% probability to not conclude an unacceptable rate of the specified AEs, if the true AE rate is 4%. If ≥ 5 pts have treatment-related AEs, then the treatment-related AE rate was considered unacceptable.
- In-breast Recurrence [ Time Frame: From registration to date of recurrence or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. ]The definition of treatment failure is histologic evidence of recurrent carcinoma, either invasive or non-invasive (except LCIS) in the ipsilateral breast. Clinical evidence of carcinoma by physical examination and/or mammograms and/or MRI will not be construed as evidence of treatment failure without biopsy proof but will be considered as suspicious for recurrence. Ipsilateral breast recurrences will be considered local (infield) if they occur within the prescription isodose volume; they will be considered peripheral if they occur between the prescription isodose volume and a volume 2 cm outside of the prescription isodose volume. Ipsilateral recurrences will be considered non-contiguous or extra field if they are beyond the peripheral volume described above.
- Freedom From Mastectomy [ Time Frame: From registration to date of mastectomy or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. ]Failure is mastectomy of the treated breast. Mastectomy rate at 3 years is reported, using the cumulative incidence with death as competing risk. Mastectomy-free survival is reported in outcome measure 10.
- Number of Patients With Detectable/Undetectable/Unevaluable Circulating Tumor Cells (CTCs) [ Time Frame: Prior to the start of radiation and 3 weeks after last radiation treatment. ]CTCs in peripheral blood were assessed using the CellSearch (trademark) system. A stringent algorithm was used to classify cell images as a CTC. A CTC must express EpCAM [epithelial cell adhesion molecule] and not leukocyte lineage-specific antigens, exhibit cytoplasmic expression of cytokeratin, and contain a nucleus that binds DAPI [4',6-doamidino-2-phenylindole]. A cell image is not a CTC if any of the previous criterion are missing. A subject is categorized as "Detectable" if the patient had a CTC and "Undetectable" if the subject had no CTCs. If neither category could be determined, then the subject was categorized as "Unevaluable."
- Treatment-related Adverse Events (AEs) Any Time [ Time Frame: From the end of radiation to end of follow-up. Will be evaluated at the time of the primary analysis. ]AEs were graded with Common Terminology Criteria for Adverse Events (CTCAE) version 4. Grade refers to the severity of the AE. The Common Terminology Criteria for Adverse Events (CTCAE) v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. The overall highest grade for each patient was computed from all reported adverse events definitely, probably, or possibly related to protocol treatment.
- Cosmesis [ Time Frame: After surgery prior to the start of radiation, 1 year from the end of radiation and 3 years from the end of radiation. Analysis occurs after all patients have been potentially followed for 3 years. ]
- Distant Metastasis-free Survival [ Time Frame: From registration to date of distant metastasis, death or last follow-up. Analysis occurs after all patient have been potentially followed for 3 years. ]Failures are appearance of ipsilateral axillary, infraclavicular, internal mammary, or supraclavicular recurrences; distant metastases confirmed radiographically and/or pathologically; or death due to any cause. Note that a distant metastases was only considered a treatment failure if accompanied by an in-breast recurrence.
- Mastectomy-free Survival [ Time Frame: From registration to date of mastectomy, death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. ]Failure is mastectomy of the treated breast or death due to any cause. Mastectomy-free survival rate at three years was estimated using the Kaplan-Meier method.
- Overall Survival [ Time Frame: From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. ]Failure is death due to any cause. Three-year overall survival rate was estimated using the Kaplan-Meier method.
- Treatment-related Adverse Events Occurring After One Year From Completion of Re-irradiation [ Time Frame: After 1 year from the end of radiation. ]AEs were graded with CTCAE version 4. The overall highest grade for each patient is computed from reported adverse events definitely, probably, or possibly related to protocol treatment occurring after one year from completion of re-irradiation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01082211
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|Principal Investigator:||Douglas W. Arthur, MD||Massey Cancer Center|