Clinical Trials /

Assessing the Accuracy of Tumor Biopsies After Chemotherapy to Determine if Patients Can Avoid Breast Surgery

NCT03188393

Description:

This phase II trial studies how well biopsy of breast after chemotherapy works in predicting pathologic response in patients with stage II-IIIA breast cancer undergoing breast conserving surgery. Tumor tissue collected from biopsy before surgery may help to check if chemotherapy destroyed the breast cancer cells and may be compared to the tumor removed during surgery to check if they are the same.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Suspended

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Assessing the Accuracy of Tumor Biopsies After Chemotherapy to Determine if Patients Can Avoid Breast Surgery
  • Official Title: A Phase II Trial Assessing the Accuracy of Tumor Bed Biopsies in Predicting Pathologic Response in Patients With Clinical/Radiologic Complete Response After Neoadjuvant Chemotherapy in Order to Explore the Feasibility of Breast Conserving Treatment Without Surgery

Clinical Trial IDs

  • ORG STUDY ID: NRG-BR005
  • SECONDARY ID: NCI-2016-01825
  • SECONDARY ID: NRG-BR005
  • SECONDARY ID: NRG-BR005
  • SECONDARY ID: NRG-BR005
  • SECONDARY ID: U10CA180868
  • NCT ID: NCT03188393

Conditions

  • Invasive Breast Carcinoma
  • Stage II Breast Cancer
  • Stage IIA Breast Cancer
  • Stage IIB Breast Cancer
  • Stage IIIA Breast Cancer

Purpose

This phase II trial studies how well biopsy of breast after chemotherapy works in predicting pathologic response in patients with stage II-IIIA breast cancer undergoing breast conserving surgery. Tumor tissue collected from biopsy before surgery may help to check if chemotherapy destroyed the breast cancer cells and may be compared to the tumor removed during surgery to check if they are the same.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the accuracy of post-neoadjuvant systemic therapy (NST) image-directed tumor bed
      biopsy for pathologic complete response (pCR), defined as resolution of both invasive disease
      and ductal carcinoma in situ (DCIS), in cases of clinical and radiologic complete response
      with trimodality imaging.

      SECONDARY OBJECTIVES:

      I. To collect axillary pathology results, surgical staging methods (sentinel lymph node
      biopsy and/or axillary lymph node dissection), and management (surgery and/or radiation) in
      order to determine axillary nodal response to neoadjuvant chemotherapy and its relationship
      to breast pCR.

      II. To correlate imaging results with pathologic nodal status following neoadjuvant
      chemotherapy for future planning of axillary management in the next study.

      III. To retrospectively assess the negative predictive value (NPV) of a trimodality imaging
      algorithm in combination with the tumor bed biopsy for predicting pCR.

      IV. To collect all trimodality imaging data to determine which combination of the trimodality
      imaging best identifies the group achieving pCR.

      V. To correlate the number of needle cores and tumor bed clip retrieval with the NPV of the
      tumor site biopsy.

      VI. To determine the clinical, imaging, pathologic, and molecular tumor factors associated
      with the highest NPVs of post-NST tumor bed biopsies.

      VII. To improve identification and selection of patients with breast and possible axillary
      pCR for future trial planning, routine biomarkers (estrogen receptor [ER], progesterone
      receptor [PR], HER2 neu, and Ki67) will be collected to allow comparison to image/clinical
      complete response (CR), and tumor bed biopsies.

      OUTLINE:

      After completion of neoadjuvant therapy, patients undergo stereotactic biopsy of breast tumor
      any time prior to breast conserving surgery. Patients then undergo breast conserving surgery
      as per standard of care. Patients may also undergo postoperative radiation therapy per
      standard of care or adjuvant therapy at the investigator's discretion.
    

Trial Arms

NameTypeDescriptionInterventions
Diagnostic (biopsy of breast)ExperimentalAfter completion of neoadjuvant therapy, patients undergo stereotactic biopsy of breast tumor any time prior to breast conserving surgery. Patients then undergo breast conserving surgery as per standard of care. Patients may also undergo postoperative radiation therapy per standard of care or adjuvant therapy at the investigator's discretion.

    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
    
              -  Patients must have had ER analysis performed on the primary breast tumor collected
                 prior to 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. Patients who have a primary tumor that is hormone
                 receptor-positive or hormone receptor-negative are eligible.
    
              -  Patients must have had HER2 testing performed on the primary breast tumor collected
                 prior to neoadjuvant chemotherapy according to the current ASCO/CAP guideline
                 recommendations for human epidermal growth factor receptor 2 testing in breast cancer;
                 patients who have a primary tumor that is HER2-positive, HER2-equivocal, or
                 HER2-negative are eligible
    
              -  Patients must have had a biopsy marker placed within the tumor bed with imaging
                 confirmation (preferably mammogram but ultrasound or magnetic resonance imaging [MRI]
                 is acceptable) of marker placement prior to neoadjuvant chemotherapy
    
              -  Patients with operable focal or multifocal (T1-T3, stage II or III invasive ductal
                 carcinoma [all receptor phenotypes]), and who have completed neoadjuvant chemotherapy
                 with a clinical complete response (by clinical examination)
    
              -  Patients with synchronous bilateral breast cancer are eligible if at least one of the
                 synchronous breast cancers has a cCR, and the side with a cCR meets criteria.
                 (Patients with previous contralateral invasive breast cancer treated with anti-cancer
                 therapy are eligible.)
    
              -  Patients must have achieved a complete or near complete radiologic tumor response on
                 breast imaging with mammogram, ultrasound, and MRI during or after completion of
                 appropriate neoadjuvant chemotherapy defined as:
    
                   -  Mammogram with malignant appearing calcification or mass ≤ 1 cm; or
    
                   -  Ultrasound with a hypoechoic area ≤ 2 cm; or
    
                   -  Breast MRI not demonstrating a residual mass with rapid rise and washout type III
                      kinetics.
    
              -  At the time of consent, the patient's intent must be to undergo breast conserving
                 therapy.
    
              -  Patient must be able to undergo stereotactic-vacuum-assisted breast biopsy with clip
                 placement after completion of neoadjuvant chemotherapy. (The patient must be enrolled
                 on the study before performing the post-neoadjuvant stereotactic-vacuum-assisted
                 breast biopsy.)
    
              -  Patient must have completed neoadjuvant chemotherapy.
    
              -  Patients with HER2-positive tumors must have received neoadjuvant anti-HER2 therapy
                 (either with all or with a portion of the neoadjuvant chemotherapy regimen), unless
                 medically contraindicated.
    
              -  Patients treated with PD-1 or PD-L1 inhibitors, CDK 4/6 inhibitors, or other
                 immune-based therapy are eligible.
    
            Exclusion Criteria:
    
              -  T4 tumors including inflammatory breast cancer
    
              -  Patients with distant metastatic disease
    
              -  Lumpectomy performed prior to study entry
    
              -  Patients with any history of prior radiation therapy in the affected breast
    
              -  Patients with a prior history of ipsilateral invasive breast cancer; (patients with
                 previous ipsilateral/contralateral DCIS or previous contralateral invasive breast
                 cancer treated with anti-cancer therapy are eligible)
    
              -  Patients with invasive lobular carcinoma
    
              -  Patients who have multicentric disease
    
              -  Patients treated with neoadjuvant hormonal therapy only are not eligible
    
              -  Patients who are medically unfit to undergo surgical resection
    
              -  Patients without breast biopsy marker documented by imaging at tumor bed site prior to
                 initiation of neoadjuvant therapy
    
              -  Patients with one or more of the following imaging criteria from any of the 3 imaging
                 modalities after completion of NCT demonstrating incomplete radiologic response are
                 not eligible:
    
                   -  Mammogram with malignant appearing calcifications or mass > 1 cm; or
    
                   -  Ultrasound with a hypoechoic area > 2 cm; or
    
                   -  Breast MRI demonstrating a residual mass with rapid rise and washout type III
                      kinetics.
    
              -  Psychiatric or addictive disorders or other conditions that, in the opinion of the
                 investigator, would preclude the patient from meeting the study requirements or
                 interfere with interpretation of study results
    
              -  Pregnancy or lactation at the time of study registration; (Note: Pregnancy testing
                 according to institutional standards for women of childbearing potential must be
                 performed within 2 weeks prior to study registration.)
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Proportion of patients with pCR
    Time Frame:Up to 18 months
    Safety Issue:
    Description:The proportion of tumor bed biopsies that are negative among those who are shown to have pCR at surgery will be determined. The point estimate and 95% confidence interval will be calculated.

    Secondary Outcome Measures

    Measure:Improvement of negative predictive value
    Time Frame:Up to 18 months
    Safety Issue:
    Description:Analysis will be performed to assess the improvement in the negative predictive value of the trimodality imaging algorithm when the results of tumor bed biopsy are added.
    Measure:Incidence of adverse events associated with tumor bed biopsy
    Time Frame:Up to 18 months
    Safety Issue:
    Description:Descriptive analysis will be performed to determine the frequencies of adverse events associated with tumor bed biopsy.
    Measure:Number of needle cores performed
    Time Frame:Up to 18 months
    Safety Issue:
    Description:Descriptive analysis will be performed to determine the distribution of the number of needle cores performed and the proportion of clips retrieved.
    Measure:Proportion of clips retrieved
    Time Frame:Up to 18 months
    Safety Issue:
    Description:Descriptive analysis will be performed.
    Measure:Residual cancer burden score
    Time Frame:Up to 18 months
    Safety Issue:
    Description:Descriptive analysis will be performed to determine the distribution of residual cancer burden score.
    Measure:Trimodality imaging algorithm +/- biopsy as a predictor of pCR
    Time Frame:Up to18 months
    Safety Issue:
    Description:Analysis will be performed to assess the improvement in the negative predictive value of the trimodality imaging algorithm when the results of tumor bed biopsy are added.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Suspended
    Lead Sponsor:NRG Oncology

    Last Updated

    August 22, 2019