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Standard or Comprehensive Radiation Therapy in Treating Patients With Early-Stage Breast Cancer Previously Treated With Chemotherapy and Surgery

NCT01872975

Description:

This randomized phase III trial studies standard or comprehensive radiation therapy in treating patients with early-stage breast cancer who have undergone surgery. Radiation therapy uses high-energy x rays to kill tumor cells. It is not yet known whether comprehensive radiation therapy is more effective than standard radiation therapy in treating patients with breast cancer

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Standard or Comprehensive Radiation Therapy in Treating Patients With Early-Stage Breast Cancer Previously Treated With Chemotherapy and Surgery
  • Official Title: A Randomized Phase III Clinical Trial Evaluating Post-Mastectomy Chestwall and Regional Nodal XRT and Post-Lumpectomy Regional Nodal XRT in Patients With Positive Axillary Nodes Before Neoadjuvant Chemotherapy Who Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: NSABP-B-51
  • SECONDARY ID: NCI-2012-03198
  • SECONDARY ID: U10CA012027
  • NCT ID: NCT01872975

Conditions

  • Stage IB Breast Cancer
  • Stage II Breast Cancer

Purpose

This randomized phase III trial studies standard or comprehensive radiation therapy in treating patients with early-stage breast cancer who have undergone surgery. Radiation therapy uses high-energy x rays to kill tumor cells. It is not yet known whether comprehensive radiation therapy is more effective than standard radiation therapy in treating patients with breast cancer

Detailed Description

      PRIMARY OBJECTIVES:

      To evaluate whether the addition of chest wall + regional nodal radiation therapy (XRT)
      after mastectomy or breast + regional nodal XRT after breast conserving surgery will
      significantly reduce the rate of events for invasive breast cancer recurrence-free interval
      (IBC-RFI) in patients who present with histologically positive axillary nodes but convert to
      histologically negative axillary nodes following neoadjuvant chemotherapy.

      SECONDARY OBJECTIVES:

      I. To evaluate whether the addition of chest wall + regional nodal XRT after mastectomy or
      breast + regional nodal XRT after breast conserving surgery will significantly prolong
      overall survival (OS) in patients who present with histologically positive axillary nodes
      but convert to histologically negative axillary nodes following neoadjuvant chemotherapy.

      II. To evaluate whether the addition of chest wall + regional nodal XRT after mastectomy or
      breast + regional nodal XRT after breast conserving surgery will significantly reduce the
      rates of events for local-regional recurrence-free interval (LRRFI) in patients who present
      with histologically positive axillary nodes but convert to histologically negative axillary
      nodes following neoadjuvant chemotherapy.

      III. To evaluate whether the addition of chest wall + regional nodal XRT after mastectomy or
      breast + regional nodal XRT after breast conserving surgery will significantly reduce the
      rate of events for distant recurrence-free interval (DRFI) in patients who present with
      histologically positive axillary nodes but convert to histologically negative axillary nodes
      following neoadjuvant chemotherapy.

      IV. To compare the rates of disease-free survival (DFS)-ductal carcinoma in situ (DCIS) by
      treatment arm.

      V. To compare the rates of second primary cancer (SPC) by treatment arm.

      VI. To compare the effect of adding XRT on the cosmetic outcomes in mastectomy patients who
      have had reconstruction.

      VII. To compare the effect of adding XRT on quality of life including arm problems,
      lymphedema, pain, and fatigue.

      VIII. To evaluate the toxicity associated with each of the radiation therapy regimens.

      IX. To determine whether computed tomography (CT)-based conformal methods
      (intensity-modulated radiation therapy [IMRT] and 3-dimensional conformal radiation therapy
      [3DCRT]) for chestwall + regional nodal XRT post mastectomy and regional nodal XRT with
      breast XRT following breast conserving surgery are feasible in a multi-institutional setting
      and whether dose-volume analyses can be established to assess treatment adequacy and to
      develop normal tissue complication probabilities (NTCP) for the likelihood of toxicity.

      X. To compare the effect of XRT in patients receiving mastectomy and in patients receiving
      lumpectomy.

      XI. To examine the role of proliferation measures as a prognosticator for patients with
      residual disease after neoadjuvant chemotherapy.

      XII. To develop predictors of the degree of reduction in local regional recurrence (LRR).

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM 1: Patients are assigned to 1 of 2 treatment groups.

      GROUP 1A: Lumpectomy patients undergo whole breast radiation therapy using IMRT or 3DCRT
      once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy
      cavity once daily 5 days a week for 1-1/2 weeks.

      GROUP 1B: Mastectomy patients do not undergo radiation therapy.

      ARM 2: Patients are assigned to 1 of 2 treatment groups.

      GROUP 2A: Lumpectomy patients undergo regional nodal radiation therapy with whole breast
      radiation therapy using IMRT or 3DCRT once daily 5 days a week for 5 weeks followed by a
      radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks.

      GROUP 2B: Mastectomy patients undergo regional nodal radiation therapy and chestwall XRT
      using IMRT or 3DCRT once daily 5 days a week for 5 weeks.

      All patients also receive systemic therapy as planned (hormonal therapy for patients with
      hormone-receptor positive breast cancer and trastuzumab or other anti-human epidermal growth
      factor receptor 2 [HER2] therapy for patients with breast cancer that is HER2-positive).

      After completion of study treatment, patients are followed up at 6, 12, 18, and 24 months
      and then yearly for 8 years.
    

Trial Arms

NameTypeDescriptionInterventions
Group 1A Lumpectomy: no regional nodal XRT with WBIActive ComparatorLumpectomy patients undergo whole breast radiation therapy using IMRT or 3D-CRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks.
    Group 1B Mastectomy: No regional nodal or chestwall XRTNo InterventionMastectomy patients do not undergo radiation therapy.
      Group 2A lumpectomy: Regional nodal XRT with WBIExperimentalLumpectomy patients undergo regional nodal radiation therapy with whole breast radiation therapy using IMRT or 3D-CRT once daily 5 days a week for 5 weeks followed by a radiation therapy boost to the lumpectomy cavity once daily 5 days a week for 1-1/2 weeks.
        Group 2B Mastectomy: Regional nodal XRT and chestwall XRTExperimentalMastectomy patients undergo regional nodal radiation therapy using IMRT or 3D-CRT once daily 5 days a week for 5 weeks.

          Eligibility Criteria

                  Inclusion Criteria:
          
                    -  The patient must have signed and dated an Institutional Review Board (IRB)-approved
                       consent form that conforms to federal and institutional guidelines
          
                    -  The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
                       of 0 or 1
          
                    -  Patient must have clinically T1-3, N1 breast cancer at the time of diagnosis (before
                       neoadjuvant therapy); clinical axillary nodal involvement can be assessed by
                       palpation, ultrasound, CT scan, magnetic resonance imaging (MRI), positron emission
                       tomography (PET) scan, or PET/CT scan
          
                    -  Patient must have had pathologic confirmation of axillary nodal involvement at
                       presentation (before neoadjuvant therapy) based on either a positive fine needle
                       aspirate (FNA) (demonstrating malignant cells) or positive core needle biopsy
                       (demonstrating invasive adenocarcinoma); the FNA or core needle biopsy can be
                       performed either by palpation or by image guidance; documentation of axillary nodal
                       positivity by sentinel node biopsy (before neoadjuvant therapy) is not permitted
          
                    -  Patients must have had estrogen receptor (ER) analysis performed on the primary
                       breast tumor before neoadjuvant therapy 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
                       progesterone receptor (PgR) must also be performed according to current ASCO/CAP
                       guideline recommendations for hormone receptor testing (http://www.asco.org)
          
                    -  Patients must have had HER2 testing performed on the primary breast tumor before
                       neoadjuvant chemotherapy according to the current ASCO/CAP guideline recommendations
                       for human epidermal growth factor receptor 2 testing in Breast Cancer
                       (http://www.asco.org); patients who have a primary tumor that is either HER2-positive
                       or HER2-negative are eligible
          
                    -  Patient must have completed a minimum of 12 weeks of standard neoadjuvant
                       chemotherapy consisting of an anthracycline and/or taxane-based regimen
          
                    -  For patients who receive adjuvant chemotherapy after surgery, a maximum of 12 weeks
                       of intended chemotherapy may be administered but must be completed before
                       randomization; (if treatment delays occur, chemotherapy must be completed within 14
                       weeks); the dose and schedule of the adjuvant chemotherapy are at the investigator's
                       discretion; Note: It is preferred that all intended chemotherapy be administered in
                       the neoadjuvant setting
          
                    -  Patients with HER2-positive tumors must have received neoadjuvant trastuzumab or
                       other anti-HER2 therapy (either with all or with a portion of the neoadjuvant
                       chemotherapy regimen), unless medically contraindicated
          
                    -  At the time of definitive surgery, all removed axillary nodes must be histologically
                       free from cancer; acceptable procedures for assessment of axillary nodal status at
                       the time of surgery include:
          
                         -  Axillary node dissection
          
                         -  Sentinel node biopsy alone or
          
                         -  Sentinel node biopsy followed by axillary node dissection
          
                         -  Note: Patients are eligible whether there is residual invasive carcinoma in the
                            surgical breast specimen or whether there is evidence of pathologic complete
                            response; patients who are found to be pathologically node-positive at the time
                            of surgery, based on sentinel node biopsy alone, are candidates for A011202, a
                            study developed by the Alliance in Oncology, an NCI Cooperative Group; if
                            A011202 is open at the investigator's institution, patients should be approached
                            about participating in the A011202 study
          
                    -  Patients with pathologic staging of ypN0(i+) or ypN0(mol+) are eligible (Note:
                       Postneoadjuvant therapy is designated with a "yp" prefix.)
          
                    -  Patient who have undergone either a total mastectomy or a lumpectomy are eligible
          
                    -  For patients who undergo lumpectomy, the margins of the resected specimen or
                       re-excision must be histologically free of invasive tumor and DCIS as determined by
                       the local pathologist; additional operative procedures may be performed to obtain
                       clear margins; if tumor is still present at the resected margin after re-excision(s),
                       the patient must undergo total mastectomy to be eligible; (patients with margins
                       positive for lobular carcinoma in situ [LCIS] are eligible without additional
                       resection)
          
                    -  For patients who undergo mastectomy, the margins must be histologically free of
                       residual (microscopic or gross) tumor
          
                    -  The interval between the last surgery for breast cancer (including re-excision of
                       margins) and randomization must be no more than 56 days; also, if adjuvant
                       chemotherapy was administered, the interval between the last chemotherapy treatment
                       and randomization must be no more than 56 days
          
                    -  The patient must have recovered from surgery with the incision completely healed and
                       no signs of infection
          
                    -  If adjuvant chemotherapy was administered, chemotherapy-related toxicity that may
                       interfere with delivery of radiation therapy should have resolved
          
                  Exclusion Criteria:
          
                    -  Definitive clinical or radiologic evidence of metastatic disease
          
                    -  T4 tumors including inflammatory breast cancer
          
                    -  Documentation of axillary nodal positivity before neoadjuvant therapy by sentinel
                       node biopsy alone
          
                    -  N2 or N3 disease detected clinically or by imaging
          
                    -  Patients with histologically positive axillary nodes post neoadjuvant therapy
          
                    -  Patients with microscopic positive margins after definitive surgery
          
                    -  Synchronous or previous contralateral invasive breast cancer or DCIS; (patients with
                       synchronous and/or previous contralateral LCIS are eligible)
          
                    -  Any prior history, not including the index cancer, of ipsilateral invasive breast
                       cancer or ipsilateral DCIS treated with radiation therapy; (patients with synchronous
                       or previous ipsilateral LCIS are eligible)
          
                    -  History of non-breast malignancies (except for in situ cancers treated only by local
                       excision and basal cell and squamous cell carcinomas of the skin) within 5 years
                       prior to randomization
          
                    -  Any radiation therapy for the currently diagnosed breast cancer prior to
                       randomization
          
                    -  Any continued use of sex hormonal therapy, e.g., birth control pills, ovarian hormone
                       replacement therapy; patients are eligible if these medications are discontinued
                       prior to randomization
          
                    -  Prior breast or thoracic radiation therapy (RT) for any condition
          
                    -  Active collagen vascular disease, specifically dermatomyositis with a creatinine
                       phosphokinase (CPK) level above normal or with an active skin rash, systemic lupus
                       erythematosus, or scleroderma
          
                    -  Pregnancy or lactation at the time of study entry; (Note: Pregnancy testing must be
                       performed within 2 weeks prior to randomization according to institutional standards
                       for women of childbearing potential)
          
                    -  Other non-malignant systemic disease that would preclude the patient from receiving
                       study treatment or would prevent required follow-up
          
                    -  Psychiatric or addictive disorders or other conditions that, in the opinion of the
                       investigator, would preclude the patient from meeting the study requirements
                
          Maximum Eligible Age:N/A
          Minimum Eligible Age:18 Years
          Eligible Gender:Female
          Healthy Volunteers:No

          Primary Outcome Measures

          Measure:IBC-RFI
          Time Frame:Time from randomization until invasive local, regional, or distant recurrence, or death from breast cancer, assessed up to 10 years
          Safety Issue:
          Description:

          Secondary Outcome Measures

          Measure:OS
          Time Frame:Time from randomization to death from any cause, assessed up to 10 years
          Safety Issue:
          Description:
          Measure:LRRFI
          Time Frame:Time from randomization to recurrence of primary cancer w/in breast or lymph nodes in ipsilateral axilla, infraclavicular fossa, or ipsilateral internal mammary chain w/out evidence distant disease, or death due to breast cancer, assessed up to 10 years
          Safety Issue:
          Description:
          Measure:DRFI
          Time Frame:Time from randomization to the development of tumor in all areas beyond local or regional limits, or death due to breast cancer, assessed up to 10 years
          Safety Issue:
          Description:
          Measure:DFS-DCIS
          Time Frame:Time from randomization to local recurrence post-mastectomy/in ipsilateral breast post-lumpectomy, regional/distant recurrence, contralateral disease, second primary cancer, or death from any cause prior to recurrence or SPC, assessed up to 10 years
          Safety Issue:
          Description:
          Measure:Time to SPC
          Time Frame:Time from randomization to the development of a second primary invasive cancer of any site excluding squamous and basal cell carcinoma of the skin, assessed up to 10 years
          Safety Issue:
          Description:
          Measure:Effect of radiation therapy on cosmetic outcome in mastectomy and lumpectomy patients as assessed by quality of life questionnaire
          Time Frame:Assessed prior to randomization, 3 months or at end of RT, and 6, 12, and 24 months from randomization
          Safety Issue:
          Description:
          Measure:Frequencies of adverse events graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
          Time Frame:Up to 30 days after completion of study treatment
          Safety Issue:
          Description:
          Measure:Molecular predictors of recurrence
          Time Frame:Tissue samples collected within 90 days after randomization
          Safety Issue:
          Description:To test the prognostic role of gene expression profiles in residual tumor tissue and to develop predictors of the degree of reduction of loco-regional recurrence.

          Details

          Phase:Phase 3
          Primary Purpose:Interventional
          Overall Status:Recruiting
          Lead Sponsor:NSABP Foundation Inc

          Last Updated

          October 4, 2016