Radiation Therapy in Treating Women With Locally Recurrent Breast Cancer Previously Treated With Repeat Breast-Preserving Surgery

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01082211
• Other study ID #: RTOG 1014
• Secondary ID: CDR0000666991
• Status: Completed
• Phase: Phase 2
• Start date: June 2010
• Est. completion date: May 20, 2022

Study information

• Verified date: May 2022
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

OBJECTIVES:

Primary

• 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.

Secondary

• 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: May 20, 2022
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed locally recurrent breast carcinoma consistent with the following cell types:

• Invasive ductal breast carcinoma

• Medullary ductal breast carcinoma

• Tubular ductal breast carcinoma

• Mucinous ductal breast carcinoma

• Lobular breast carcinoma

• Ductal carcinoma in situ (DCIS)

• No Paget disease of the nipple

• Target lumpectomy cavity must be clearly defined and the target lumpectomy cavity/ whole-breast reference volume must be < 30% based on a post-operative, pre-treatment CT scan

• Tumor size = 3 cm in greatest dimension on pathologic specimen

• Negative histologic margins of resection and no tumor on ink following breast-preserving surgery of local recurrence (Re-excision is permitted to achieve negative margins)

• Axilla negative or = 3 positive lymph nodes without extracapsular extension

• If the in-breast recurrence is DCIS and/or microinvasive disease, a sentinel lymph node (SLN) evaluation is not required, but if performed:

• Patients with a negative sentinal lymph node (SLN) biopsy are eligible for enrollment

• Patients with a positive SLN biopsy require an axillary lymph node (ALN) dissection (ALND is not required if the SLN is not identified)

• Patient is eligible if 0-3 positive ALNs without extracapsular extension is documented

• If the in-breast recurrence is invasive disease and:

• No prior ALN dissection or SLN dissection only:

• Patient is required to undergo axillary evaluation with either a SLN or ALN dissection

• If the SLN is not identified or if the SLN is positive for metastatic disease then an ALN dissection is required

• Patient is eligible for enrollment if encounter 0-3 positive lymph nodes without extracapsular extension

• • Prior ALN dissection: negative clinical exam: patient is eligible for enrollment

• It is recommended, but not required, that the patient undergo ultrasound evaluation of the axilla and the lymph node draining regions of the breast; any suspicious areas are to be biopsied and if positive followed with an ALN dissection

• Patient is eligible for enrollment if biopsies are negative or 0-3 axillary lymph nodes without extracapsular extension are encountered

• Prior ALN dissection: positive clinical exam: biopsy required

• If biopsy is negative, patient is eligible for enrollment

• If biopsy is positive an ALN dissection is required

• Patient is eligible for enrollment if biopsies are negative or 0-3 axillary lymph nodes without extracapsular extension encountered

• Ipsilateral breast mammogram and MRI within 120 days prior to study entry

• Contralateral breast mammogram within 12 months of study entry

• For invasive in-breast recurrence, no more than 120 days since whole-body (positron emission tomography) PET-CT scan OR CT scan of the chest, abdomen, and pelvis, and bone scan

• No multicentric ipsilateral breast recurrence or regional recurrence (other than axilla)

• Patients must have a breast technically amenable to partial-breast irradiation

• No metastatic disease documented by physical exam or radiographic evaluation (for patients with invasive disease)

• No skin involvement

• No prior contralateral mastectomy

• Estrogen and progesterone status must be known

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1

• Menopausal status not specified

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other invasive malignancy within the past 3 years except ipsilateral breast cancer and/or nonmelanoma skin cancer

• No collagenous diseases, specifically systemic lupus erythematosus, scleroderma, or dermatomyositis

• No psychiatric or addictive disorders that would preclude obtaining informed consent

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 2 weeks since prior chemotherapy and recovered

• No concurrent intensity-modulated radiotherapy

• No concurrent chemotherapeutic agents, including trastuzumab

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Canada	Cross Cancer Institute at University of Alberta	Edmonton	Alberta
United States	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	JFK Medical Center	Atlantis	Florida
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	Barberton Citizens Hospital	Barberton	Ohio
United States	Memorial Sloan-Kettering Cancer Center - Basking Ridge	Basking Ridge	New Jersey
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center	Burbank	California
United States	Sands Cancer Center	Canandaigua	New York
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Central Maryland Oncology Center	Columbia	Maryland
United States	Memorial Sloan-Kettering Cancer Center	Commack	New York
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	McLaren Cancer Institute	Flint	Michigan
United States	Tate Cancer Center at Baltimore Washington Medical Center	Glen Burnie	Maryland
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Cape Cod Hospital	Hyannis	Massachusetts
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	St. Barnabas Medical Center Cancer Center	Livingston	New Jersey
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Community Memorial Hospital Cancer Care Center	Menomonee Falls	Wisconsin
United States	Columbia Saint Mary's Hospital - Ozaukee	Mequon	Wisconsin
United States	Columbia-Saint Mary's Cancer Care Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	Arizona Center for Cancer Care - Peoria	Peoria	Arizona
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	Highland Hospital of Rochester	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	University Radiation Oncology at Parkridge Hospital	Rochester	New York
United States	Memorial Sloan-Kettering Cancer Center - Rockville Centre	Rockville Centre	New York
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Barnes-Jewish West County Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center	Sleepy Hollow	New York
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Grade 3+ Treatment-related Skin, Fibrosis, and Breast Pain Adverse Events	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.	From the end of radiation to 1 year.
Secondary	In-breast Recurrence	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.	From registration to date of recurrence or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
Secondary	Freedom From Mastectomy	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.	From registration to date of mastectomy or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
Secondary	Number of Patients With Detectable/Undetectable/Unevaluable Circulating Tumor Cells (CTCs)	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."	Prior to the start of radiation and 3 weeks after last radiation treatment.
Secondary	Treatment-related Adverse Events (AEs) Any Time	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.	From the end of radiation to end of follow-up. Will be evaluated at the time of the primary analysis.
Secondary	Distant Metastasis-free Survival	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.	From registration to date of distant metastasis, death or last follow-up. Analysis occurs after all patient have been potentially followed for 3 years.
Secondary	Mastectomy-free Survival	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.	From registration to date of mastectomy, death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
Secondary	Overall Survival	Failure is death due to any cause. Three-year overall survival rate was estimated using the Kaplan-Meier method.	From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
Secondary	Treatment-related Adverse Events Occurring After One Year From Completion of Re-irradiation	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.	After 1 year from the end of radiation.
Secondary	Change in Patient-Reported Cosmetic Outcomes From Baseline to 12-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS)	The Breast Cancer Treatment Outcome Scale (BCTOS) is a 22-item tool to assess cosmetic results using patient self-reports. This brief self-report instrument has high reliability and validity, and it has been used in a variety of previous studies on recovery from breast cancer treatment. It is comprised of three subscales (functional status, cosmetic status, and breast specific pain). Response options for each BCTOS item form a four-point Likert scale evaluating the differences between the treated and the untreated breast (1=no, 2=slight, 3=moderate, 4=large difference). The score for each subscale is the mean of the ratings over all items belonging to that specific subscale. Change was calculated as the value at 12 months minus the value at baseline. A positive change reflects a decline at 12 months and a negative change reflects an improvement at 12 months.	Baseline and 12 months from the start of radiation treatment.
Secondary	Change in Patient-Reported Cosmetic Outcomes From Baseline to 36-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS)	The Breast Cancer Treatment Outcome Scale (BCTOS) is a 22-item tool to assess cosmetic results using patient self-reports. This brief self-report instrument has high reliability and validity, and it has been used in a variety of previous studies on recovery from breast cancer treatment. It is comprised of three subscales (functional status, cosmetic status, and breast specific pain). Response options for each BCTOS item form a four-point Likert scale evaluating the differences between the treated and the untreated breast (1=no, 2=slight, 3=moderate, 4=large difference). The score for each subscale is the mean of the ratings over all items belonging to that specific subscale. Change was calculated as the value at 36 months minus the value at baseline. A positive change reflects a decline at 36 months and a negative change reflects an improvement at 36 months.	Baseline and 36 months from the start of radiation treatment.
Secondary	Number of Patients With Good/Excellent Cosmesis Using the NRG Oncology/Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale	Physicians rated cosmesis using a 4 point NRG Oncology/RTOG established criteria scale: Excellent - when compared to the untreated breast or the original appearance of the breast, there is minimal/no difference in the size or shape of the treated breast.; Good - there is a slight difference in the size or shape of the treated breast as compared to the opposite breast or the original appearance of the treated breast.; Fair - obvious differences in the size and shape of the treated breast. This change involves quarter or less of the breast.; Poor - marked change in the appearance of the treated breast involving more than a quarter of the breast tissue.	Baseline,12, and 36 Months from the start of radiation treatment.
Secondary	12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale	Patient-Reported BCTOS is comprised of 3 subscales (functional status, cosmetic status, breast specific pain). Responses for each item form a 4-point Likert scale evaluating the differences between the treated and untreated breast (1=no, 2=slight, 3=moderate, 4=large difference). Higher scores reflect poorer outcomes.; Physicians rated cosmesis using a 4 point NRG Oncology/RTOG established criteria scale: Excellent - when compared to the untreated breast or the original appearance of the breast, there is minimal/no difference in the size or shape of the treated breast.; Good - there is a slight difference in the size or shape of the treated breast as compared to the opposite breast or the original appearance of the treated breast.; Fair - obvious differences in the size and shape of the treated breast. This change involves quarter or less of the breast.; Poor - marked change in the appearance of the treated breast involving more than a quarter of the breast tissue.	12 Months from the start of radiation treatment.