NCT01349322Active, not recruitingPhase 3
A Phase III Trial of Accelerated Whole Breast Irradiation With Hypofractionation Plus Concurrent Boost Versus Standard Whole Breast Irradiation Plus Sequential Boost for Early-Stage Breast Cancer
Radiation Therapy Oncology Group807 sites in 1 country2,354 target enrollmentStarted: May 24, 2011Last updated:
Conditions
Interventions
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Enrollment
- 2,354
- Locations
- 807
- Primary Endpoint
- Percentage of Participants With In-breast Recurrence (Local Failure)
Study Overview
Brief Summary
RATIONALE: It is not yet know whether higher per daily radiation therapy is equally as effective as standard per daily radiation therapy in treating breast cancer.
PURPOSE: This randomized phase III trial studies how well an accelerated course of higher per daily radiation therapy with concomitant boost works compared to standard per daily radiation therapy with a sequential boost in treating patients with early-stage breast cancer that was removed by surgery.
Detailed Description
OBJECTIVES:
Primary
- To determine whether an accelerated course of hypofractionated whole-breast irradiation (WBI) including a concomitant boost to the tumor bed in 15 fractions following lumpectomy will prove to be non-inferior in local control to a regimen of standard WBI with a sequential boost following lumpectomy for early-stage breast cancer patients.
Secondary
- To determine whether breast-related symptoms and cosmesis from accelerated WBI that is hypofractionated (in only 3 weeks) with a concomitant boost is non-inferior to standard WBI with sequential boost.
- To determine whether the risk of late cardiac toxicity in patients with left-sided breast cancer treated with hypofractionation will be non-inferior to conventional fractionated radiation therapy (RT) based upon analysis of radiation dosimetry from CT-based treatment planning and normal tissue complication probability (NTCP) calculations.
- To determine whether CT-based conformal methods intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for WBI are feasible in a multi-institutional setting following lumpectomy in early-stage breast cancer patients and whether dose-volume analyses can be established to assess treatment adequacy and likelihood of toxicity.
- To determine that cosmetic results and breast-related symptoms 3 years after hypofractionated breast radiation with concomitant boost will not be inferior to that obtained 3 years after WBI with sequential boost.
- To determine whether future correlative studies can identify individual gene expressions and biological host factors associated with toxicity and/or local recurrence from standard and hypofractionated WBI.
- If shown to be non-inferior, to then determine if accelerated course of hypofractionated WBI including a concomitant boost to the tumor bed in 15 fractions following lumpectomy will prove to be superior in local control to a regimen of standard WBI with a sequential boost following lumpectomy for early-stage breast cancer patients.
- To determine whether treatment costs for hypofractionated WBI with concomitant boost are not higher than WBI with sequential boost.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Pathologically proven diagnosis of breast cancer resected by lumpectomy and whole breast irradiation with boost without regional nodal irradiation planned
- •The patient must be female
- •The patient must meet at least one of the three following criteria:
- •A. Pathological stage I, II Breast Cancer AND at least one of the following:
- •Age < 50 years or
- •Positive axillary nodes or
- •Lymphovascular space invasion or
- •2 or more close resection margins (> 0 mm to ≤ 2 mm) or
- •1 close resection margin and extensive intraductal component (EIC) [Per College of American Pathologist (CAP) Recommendation] or
- •Focally positive resection margins or
- •Non-hormone sensitive breast cancer (estrogen receptor (ER)- and progesterone receptor(PR)-negative) or
- •Grade III histology or
- •Oncotype recurrence score > 25 or
- •B. Pathological stage 0 breast cancer with nuclear grade 3 ductal carcinoma in situ (DCIS) and patient age <50 years or
- •C. Post-neoadjuvant pathological 0, I, II breast cancer resected by lumpectomy after neoadjuvant systemic therapy
- •Study entry must be within 50 days from whichever comes later: last surgery (breast or axilla) or last chemotherapy. The day of surgery is Day "0".
- •If multifocal breast cancer, then it must have been resected through a single lumpectomy incision with negative margins
- •Breast-conserving surgery with margins defined as follows: (also see 3.1.3 for eligibility)
- •Negative margins defined as no tumor at the resected specimen edge.
- •Close resection margins > 0 mm to ≤ 2 mm. as follows:
- •One close resection margin and EIC (per College of American Pathologist (CAP) Recommendation)
- •2 or more close resection margins.
- •A focally positive resection margin
- •For invasive breast cancer the axilla must be staged by one of the following:
- •Sentinel node biopsy alone, if sentinel node is negative, i.e. any of the following:
- •pN0: no regional lymph node metastasis identified histologically,
- •pN0(i-): pN0 and immunohistochemical (IHC) negative, or
- •pN0(i+): pN0 and IHc positive;
- •Sentinel node biopsy alone, OR followed by axillary node dissection per investigator discretion, for clinically node negative patients as described below:
- •microscopic sentinel node positive (pN1mic)
- •one or two sentinel nodes positive (pN1) without extracapsular extension
- •negative sentinel node biopsy after neoadjuvant chemotherapy
- •Axillary node dissection is required following sentinel node (SN) biopsy with a minimum total of 6 axillary nodes if any of the following exist:
- •for > 2 positive SN
- •any positive SN biopsy after neoadjuvant chemotherapy
- •for clinically (by either imaging or examination) T3 disease
- •for extracapsular extension
- •Axillary dissection alone (with a minimum of 6 axillary nodes)
- •CT-imaging of the ipsilateral breast within 28 days prior to study entry for the radiation treatment planning. Must be able to delineate on CT scan the extent of the target lumpectomy cavity for boost
- •Appropriate stage for protocol entry, including no clinical evidence for distant metastases, based upon the following minimum diagnostic workup:
- •History/physical examination, including breast exam (inspection and palpation of the breasts) and documentation of weight and Zubrod Performance Status of 0-2 within 28 days prior to study entry;
- •Right and left mammography within 90 days of diagnostic biopsy establishing diagnosis
- •Patients must have had ER analysis performed on the primary breast tumor prior to study entry according to current American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) Guideline Recommendations for hormone receptor testing. If negative for ER, assessment of PR must also be performed according to current ASCO/CAP Guideline Recommendations for hormone receptor testing (http://www.asco.org)
- •Complete blood count (CBC)/differential obtained within 14 days prior to study entry, with adequate bone marrow function defined as follows:
- •Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3
- •Platelets ≥ 75,000 cells/mm3
- •Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
- •Women of childbearing potential must have a negative urine or serum pregnancy test within 14 days of study entry
- •Women of childbearing potential must be non-pregnant and non-lactating and willing to use medically acceptable form of contraception during radiation therapy
- •Patient must provide study specific informed consent prior to study entry
- +1 more not shown
Exclusion Criteria
- •American Joint Committee on Cancer (AJCC) pathologic T4, N2 or N3, M1 pathologic stages III or IV breast cancer
- •Treatment plan that includes regional node irradiation
- •Prior invasive non-breast malignancy (except non-melanomatous skin cancer, carcinoma in situ of the cervix) unless disease free for a minimum of 5 years prior to study entry
- •Prior invasive or in-situ carcinoma of the breast [-prior lobular carcinoma in situ (LCIS) is eligible]
- •Two or more breast cancers not resectable through a single lumpectomy incision
- •Bilateral breast cancer
- •DCIS only (without an invasive component) and age ≥ 50 years
- •DCIS nuclear grade 1 or 2 only (without an invasive component) and age < 50 years
- •Invasive breast cancer and low risk for 5-year in breast recurrence after lumpectomy with negative margins that does not meet one of the eligibility factors in 3.1.
- •Unable to delineate on CT scan the extent of the target lumpectomy cavity for boost (Placement of surgical clips to assist in treatment planning of the boost is strongly recommended, see Section 6.4.2 for details)
- •Suspicious unresected microcalcification, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign
- •Non-epithelial breast malignancies such as sarcoma or lymphoma
- •Paget's disease of the nipple
- •Male breast cancer
- •Prior radiotherapy to the breast or prior radiation to the region of the ipsilateral breast that would result in overlap of radiation therapy fields
- •Intention to administer concurrent chemotherapy for current breast cancer.
- •Severe, active co-morbidity, defined as follows:
- •Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- •Transmural myocardial infarction within the last 6 months
- •Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
- •Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration;
- •Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol
- •Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive
- •Pregnancy or women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception
- •Active systemic lupus, erythematosus, or any history of scleroderma, dermatomyositis with active rash
- •Medical, psychiatric or other condition that would prevent the patient from receiving the protocol therapy or providing informed consent
Arms & Interventions
Whole breast irradiation + sequential boost
Active Comparator
Standard fractionation whole breast irradiation (WBI) with sequential boost.
Intervention: Standard fractionation whole breast irradiation (Radiation)
Whole breast irradiation + sequential boost
Active Comparator
Standard fractionation whole breast irradiation (WBI) with sequential boost.
Intervention: Sequential boost (Radiation)
Hypofractionated whole breast irradiation + concurrent boost
Experimental
Hypofractionated whole breast (H-WBI) irradiation with a concurrent boost
Intervention: Hypofractionated whole breast irradiation (Radiation)
Hypofractionated whole breast irradiation + concurrent boost
Experimental
Hypofractionated whole breast (H-WBI) irradiation with a concurrent boost
Intervention: Concurrent boost (Radiation)
Outcomes
Primary Outcomes
Percentage of Participants With In-breast Recurrence (Local Failure)
Time Frame: From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are reported here.
In-breast recurrence (IBR) is defined as any of the following: invasive local recurrence-ipsilateral breast (within treatment field); invasive local recurrence-ipsilateral breast (outside treatment field); non-invasive local recurrence-ipsilateral breast (within treatment field); or non-invasive local recurrence-ipsilateral breast (outside treatment field). Time to IBR is defined as time from randomization to the date of first IBR, last known follow-up (censored), or death without IBR (competing risk). IBR rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 5-year rates are provided.
Secondary Outcomes
- Percentage of Participants Alive Without Disease(From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are provided here.)
- Percentage of Participants With a Physician-reported Cosmetic Score of Excellent or Good at 3 Years(3 years)
- Translational Research of Single Nucleotide Polymorphisms (SNPs) in Transforming Growth Factor Beta 1 (TGFB1) and Ataxia-Telangiesctasia Mutated (ATM) Genes(From randomization to last follow-up.)
- Percentage of Participants Alive Without Distant Disease(From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are provided here.)
- Correlation Between Dose-volume Data and Both Adverse Events and Efficacy(From randomization to end of follow-up.)
- Percentage of Participants Alive(From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are provided here.)
- Number of Participants by Highest Grade Adverse Event Reported as Definitely, Probably, or Possibly Related to Protocol Treatment(From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years.)
- Change in Breast Cancer Treatment Outcome Scale (BCTOS) Cosmesis Subscale Score From Baseline to 3 Years(Baseline and 3 years)
- Treatment Cost(From randomization to end of treatment.)
Investigators
Study Sites (807)
Loading locations...
Similar Trials
Completed
Not Applicable
RAPID: Randomized Trial of Accelerated Partial Breast IrradiationBreast CancerNCT00282035Ontario Clinical Oncology Group (OCOG)2,135
Completed
Phase 3
Study Comparing Whole Breast Radiotherapy With a Daily Versus a Weekly TumorBreast CancerNCT01000662NYU Langone Health412
Unknown
Phase 2
Accelerated Partial Breast Radiotherapy With Either Mammosite or Intensity Modulated RadiotherapyBreast CancerNCT01185145Rocky Mountain Cancer Centers291
Completed
Phase 2
Accelerated Partial Breast Radiation Therapy Using High-Dose Rate Brachytherapy in Treating Patients With Early Stage Breast Cancer After SurgeryDuctal Breast Carcinoma In SituEstrogen Receptor PositiveInvasive Breast CarcinomaProgesterone Receptor PositiveStage IA Breast CancerStage IB Breast CancerStage IIA Breast CancerNCT02526498Rutgers, The State University of New Jersey200
Completed
Phase 2
Hypofractionated Radiotherapy for Limited Stage Small Cell Lung CancerSmall Cell CarcinomaLung NeoplasmNCT00907569AHS Cancer Control Alberta2