Clinical trial NCT01082211: Radiation Therapy in Treating Women With Locally Recurrent Breast Cancer Previously Treated With Repeat Breast-Preserving Surgery
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: invasive ductal breast carcinoma
medullary ductal breast carcinoma with lymphocytic infiltrate
invasive lobular breast carcinoma
tubular ductal breast carcinoma
mucinous ductal breast carcinoma
ductal breast carcinoma in situ
lobular breast carcinoma in situ
recurrent breast cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2010-03-08
Enrollment: 65
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Grade 3+ Treatment-related Skin, Fibrosis, and Breast Pain Adverse Events
timeFrame: From the end of radiation to 1 year.
Secondary outcomes:
measure: In-breast Recurrence
timeFrame: From registration to date of recurrence or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
measure: Freedom From Mastectomy
timeFrame: From registration to date of mastectomy or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
measure: Number of Patients With Detectable/Undetectable/Unevaluable Circulating Tumor Cells (CTCs)
timeFrame: Prior to the start of radiation and 3 weeks after last radiation treatment.
measure: Treatment-related Adverse Events (AEs) Any Time
timeFrame: From the end of radiation to end of follow-up. Will be evaluated at the time of the primary analysis.
measure: Distant Metastasis-free Survival
timeFrame: From registration to date of distant metastasis, death or last follow-up. Analysis occurs after all patient have been potentially followed for 3 years.
measure: Mastectomy-free Survival
timeFrame: From registration to date of mastectomy, death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
measure: Overall Survival
timeFrame: From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years.
measure: Treatment-related Adverse Events Occurring After One Year From Completion of Re-irradiation
timeFrame: After 1 year from the end of radiation.
measure: Change in Patient-Reported Cosmetic Outcomes From Baseline to 12-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS)
timeFrame: Baseline and 12 months from the start of radiation treatment.
measure: Change in Patient-Reported Cosmetic Outcomes From Baseline to 36-Months as Measured by the Breast Cancer Treatment Outcome Scale (BCTOS)
timeFrame: Baseline and 36 months from the start of radiation treatment.
measure: Number of Patients With Good/Excellent Cosmesis Using the NRG Oncology/Radiation Therapy Oncology Group (RTOG) Cosmetic Rating Scale
timeFrame: Baseline,12, and 36 Months from the start of radiation treatment.
measure: 12-Month BCTOS Mean Subscale Scores by 12-Month NRG Oncology/RTOG Cosmetic Rating Scale
timeFrame: 12 Months from the start of radiation treatment.
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Arizona Center for Cancer Care - Peoria
state: Arizona
city: Burbank
country: United States
facility: Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Atlantis
country: United States
facility: JFK Medical Center
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Springfield
country: United States
facility: Cancer Institute at St. John's Hospital
state: Illinois
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: St. Agnes Hospital Cancer Center
state: Maryland
city: Columbia
country: United States
facility: Central Maryland Oncology Center
state: Maryland
city: Glen Burnie
country: United States
facility: Tate Cancer Center at Baltimore Washington Medical Center
state: Maryland
city: Hyannis
country: United States
facility: Cape Cod Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Battle Creek
country: United States
facility: Battle Creek Health System Cancer Care Center
state: Michigan
city: Flint
country: United States
facility: McLaren Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Health Care
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak Campus
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute at Saint Mary's - Saginaw
state: Michigan
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish West County Hospital
state: Missouri
city: Basking Ridge
country: United States
facility: Memorial Sloan-Kettering Cancer Center - Basking Ridge
state: New Jersey
city: Livingston
country: United States
facility: St. Barnabas Medical Center Cancer Center
state: New Jersey
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Marlton
country: United States
facility: Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: Canandaigua
country: United States
facility: Sands Cancer Center
state: New York
city: Commack
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: Highland Hospital of Rochester
state: New York
city: Rochester
country: United States
facility: University Radiation Oncology at Parkridge Hospital
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan-Kettering Cancer Center - Rockville Centre
state: New York
city: Sleepy Hollow
country: United States
facility: Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Barberton
country: United States
facility: Barberton Citizens Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital Cancer Center
state: Ohio
city: Abington
country: United States
facility: Rosenfeld Cancer Center at Abington Memorial Hospital
state: Pennsylvania
city: Drexel Hill
country: United States
facility: Delaware County Regional Cancer Center at Delaware County Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Reading
country: United States
facility: McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Menomonee Falls
country: United States
facility: Community Memorial Hospital Cancer Care Center
state: Wisconsin
city: Mequon
country: United States
facility: Columbia Saint Mary's Hospital - Ozaukee
state: Wisconsin
city: Milwaukee
country: United States
facility: Columbia-Saint Mary's Cancer Care Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute at University of Alberta
state: Alberta
Study officials:
affiliation: Massey Cancer Center
name: Douglas W. Arthur, MD
role: PRINCIPAL_INVESTIGATOR
References: