Eliminating Surgery or Radiotherapy after Neoadjuvant Systemic Therapy in Treating Patients with Breast Cancer
This clinical trial studies three groups of different patients with eliminating surgery or radiotherapy after systemic therapy when no evidence of disease is found.
Inclusion Criteria
- COHORT A1/A2: Patients on this portion of the study can receive radiation treatment at any MD Anderson Cancer Center or any outside hospital and may be enrolled prior to, during, or following neoadjuvant systemic therapy provided they meet the following eligibility and ineligibility requirements noted below
- COHORT A1/A2: Pathologically confirmed unicentric invasive breast cancer defined as radiologic clinical stage T1 or T2 (=< 5 cm), N0 or N1 (=< 4 abnormal axillary nodes on initial ultrasound), clinical stage M0
- COHORT A1/A2: HER2 positive (immunohistochemistry [IHC] 3+ and or fluorescence in situ hybridization [FISH] amplified) or triple receptor negative (triple negative [TN], estrogen receptor [ER]/progesterone receptor [PR] < 10% HER2 negative [IHC 1+ or 2+ FISH non-amplified]) receiving any standard routine clinical NST regimen
- COHORT A1/A2: Patient desires breast conserving therapy
- COHORT A1/A2: Age 40 years or older; this age cutoff is justified because breast cancers in women under the age of 40 are known to have a significantly higher risk of IBTR presumably due to underlying biologic differences
- COHORT A1/A2: Female sex
- COHORT A1/A2: If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed prior to study registration and the patient must have no evidence of disease for this prior non-breast cancer
- COHORT A1/A2: Patient must have an initial nodal ultrasound that does not demonstrate more than four suspicious lymph nodes, any suspicious lymph nodes should be biopsied to determine if nodal metastatic disease present
- COHORT A1/A2: Patient and treatment team understands that the breast lesion size on final breast imaging must be less than or equal to 2 cm and the size documented on the radiology reports after neoadjuvant systemic therapy prior to the biopsy procedure being performed on study. If the biopsy shows residual carcinoma or any atypical or suspicious lesions the patient will be taken off study following standard surgery for study completion
- COHORT B1/B2: Patients on this portion of the study will be limited to receive radiation treatment at MD Anderson Cancer Center or other approved locations and must be enrolled prior to any neoadjuvant systemic therapy provided they meet the following eligibility and ineligibility requirements noted below
- COHORT B1/B2: ER and/or PR positive, HER2 negative
- COHORT B1/B2: Clinical stage T1N0M0, unicentric non-lobular breast cancer, no lymphovascular space invasion
- COHORT B1/B2: At least 40 years of age
- COHORT B1/B2: Oncotype =< 25 if age >= 50 years
- COHORT B1/B2: Oncotype 0-20 and tumor size =< 1.5 cm if age 40-49 years
- COHORT B1/B2: Patient agrees to take anti-estrogen therapy and is interested in breast conservation
- COHORT B1/B2: Female sex
- COHORT B1/B2: If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed prior to study registration and the patient must have no evidence of disease for this prior non-breast cancer
- COHORT B1/B2: No history of prior radiation to the area of the breast that would require protocol-mandated treatment
- COHORT C1/C2: Patients on this portion of the study can receive surgical treatment at any MD Anderson Cancer Center or any outside hospital and may be enrolled prior to, during, or following neoadjuvant systemic therapy provided they meet the following eligibility and ineligibility requirements noted below
- COHORT C1/C2: Patients on C1 should have pathologically confirmed invasive breast cancer defined as radiologic clinical stage T1 or T2 (=< 5 cm), N0, clinical stage M0 cancer defined as radiologic clinical stage T1 or T2 (≤ 5 cm), N0, clinical stage M0 and HER2 positive (IHC 3+ and or FISH amplified) receiving any standard routine clinical NST regimen containing her-2 directed therapy OR pathologically confirmed invasive breast cancer defined as radiologic clinical stage T1 (≤ 2 cm), N0, clinical stage M0 and triple negative, receiving any standard routine clinical NST regimen. Patients on C2 should have pathologically confirmed invasive breast cancer defined as radiologic clinical stage T1 or T2 (≤ 5 cm), N0 or N1, clinical stage M0 and HER2 positive (IHC 3+ and or FISH amplified) receiving any standard routine clinical NST regimen containing her-2 directed therapy OR triple negative, receiving any standard routine clinical NST regimen
- COHORT C1/C2: For cohort C1/C2 patients participating in the optional pretreatment biopsy, the patient should be able undergo biopsy or surgery of the primary tumor site of suspected or proven invasive breast cancer and should be planned to receive neoadjuvant systemic therapy
- COHORT C1/C2: Patient desires breast conserving therapy
- COHORT C1/C2: Patients on C1 should be age 30 years or older if HER2 positive or age 50 or older if HER2 negative (triple negative). Patients on C2 should be age 30 years or older
- COHORT C1/C2: Female sex
- COHORT C1/C2: If the patient has a history of a prior non-breast cancer, all treatment for this cancer must have been completed prior to study registration and the patient must have no evidence of disease for this prior non-breast cancer
- COHORT C1/C2:: Patient must have an initial nodal ultrasound; any suspicious lymph nodes should be biopsied to determine if nodal metastatic disease present
- COHORT C1/C2: Patient must have no evidence of residual invasive tumor or ductal carcinoma in situ (DCIS) on pathologic review of the lumpectomy surgical specimen
- COHORT C1/C2: Patient must have no evidence of metastatic disease involving the lymph nodes on pathologic review of the lymph node surgical specimen
- COHORT C1/C2: Unifocal disease or limited multifocal disease that can be excised in a single lumpectomy specimen
- COHORT D: Patients on this portion of the study meet all eligibility requirements for cohort C, but have not enrolled onto the study to omit radiation. Patients in Cohort D can be identified at the time of diagnosis or prior to lumpectomy. They are not required to participate in one of the treatment arms of the study, but can ultimately choose to move to an omission Cohort at a later time point
- COHORT D: Patients with triple negative or her-2 positive tumor who are amenable to breast conserving treatment and have received or are planned for neoadjuvant systemic therapy prior to surgery are eligible for Cohort D
- COHORT D: Eligible patients in cohort D who have undergone optional ARTIDIS biopsies of the primary breast tumor at the time of diagnosis, prior to starting neoadjuvant therapy, or following completion of systemic therapy, at the time of surgery, may later move to Cohort A or C if they meet all eligibility requirements and ultimately desire surgery or radiation omission
Exclusion Criteria
- Radiologic evidence for a stage T3 or clinical stage T4 breast cancer in Cohort A1/A2/C1/C2; radiologic evidence for a stage T2-T3 or clinical stage T4 breast cancer in Cohort B1/B2
- Clinical or pathologic evidence for distant metastases
- Prior diagnosis of invasive or ductal carcinoma in situ breast cancer in the ipsilateral breast
- Clinical evidence of progression of disease > 20% in the breast or new evidence of nodal metastases
- Patient is known to be pregnant
- Patient is participating in a NST protocol in which surgical excision of the breast and or lymph nodes are required in Cohort A1/A2/B1/B2
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02945579.
Locations matching your search criteria
United States
Arizona
Gilbert
Florida
Jacksonville
Minnesota
Rochester
New Jersey
Voorhees
North Carolina
Charlotte
Pennsylvania
Pittsburgh
Texas
Conroe
Houston
League City
Sugar Land
PRIMARY OBJECTIVES:
I. To determine the 6 months (mo), 1, 2, 3, 5, 7 and 10-year biopsy confirmed ipsilateral breast tumor recurrence rate (IBTR, invasive, and/or in situ) among patients who do not undergo surgery. (Cohort A1 and A2)
II. To determine the pathologic complete response (pCR) rate 6 or 12 months after radiation therapy based on image-guided biopsy. (Cohort B)
III. To determine the 6 mo, 1, 2, 3, 5, 7 and 10-year ipsilateral breast tumor recurrence rate among patients who undergo surgery alone without radiation. (Cohort C1/C2/D)
SECONDARY OBJECTIVES:
I. To determine the 6 mo, 1, 2, 3, 5, 7 and 10-year biopsy confirmed ipsilateral breast tumor recurrence rate (IBTR, invasive and/or in situ) among patients who do not undergo surgery. (Cohort B)
II. To determine the number (%) of patients where final biopsy reveals residual disease and quantify the residual disease (residual cancer burden, RCB) determined by routine pathologic examination of surgery specimens.
III. To assess baseline, 6 months, 1, 3, 5, 7 and 10 years decisional comfort of clinical trial participation using the Decisional Regret Scale (DRS).
IV. To determine patient-reported cosmetic outcome, breast pain, and functional status using the Breast Cancer Treatment Outcomes Scale (BCTOS) at baseline, 6 months, 1, 3, 5, 7, and 10 years.
V. To determine the 6 mo, 1, 2, 3, 5, 7, and 10 years incidence of ipsilateral breast and nodal recommendation and performance of biopsy based on breast imaging follow-up.
VI. Correlate "liquid biopsy" analyses (after neoadjuvant systemic therapy [NST], 6 months and one year postradiotherapy or surgery) among protocol participants with pCR, utilizing circulating tumor cells (CTCs) and circulating tumor-deoxyribonucleic acid (DNA) (ctDNA).
VII. Among patients who decide to proceed with routine surgery, record the results of final biopsy compared with routine pathologic examination of surgery specimens.
VIII. To determine patient-reported quality of life using the Functional Assessment of Cancer Therapy-Breast version 4 (FACT B+4) instrument at baseline, 6 months, 1, 3, 5, 7 and 10 years after treatment.
IX. To explore if radiation genomic sensitivity scores and Oncotype performed on the initial diagnostic core biopsy specimen correlate with pCR rates in Cohort B.
X. To determine if changes in blood-based ribonucleic acid (RNA) sequencing are elicited with radiation in Cohort B, measured at baseline, at the first 4-6 week follow-up after radiation, and at the 6 month post-radiation follow-up.
XI. To determine the 3 year rate of tumor control/ progression free survival (PFS) (Cohort B).
XII. To determine whether nanomechanical biomarkers or quantification of stromal and tumor infiltrating lymphocytes (TILS) can predict for low risk of local recurrence in exceptional responders who omit radiation therapy(Cohort C1/C2/D).
XIII. To record 6 mo, 1, 2, 3, 5, 7, and 10 year breast cancer disease-free and overall survival (Cohorts A/B/C/D).
XIV. Correlate nanomechanical biomarker analyses with pCR and/or local recurrence in patients with triple negative or her-2 positive breast cancer treated with lumpectomy +/- radiation. (Cohort D)
OUTLINE: Patients are assigned to 1 of 4 cohorts.
COHORT A1 and A2: Patients undergo image-guided biopsy at any point after completing chemotherapy and prior to radiation therapy. Patients whose biopsy results show no evidence of disease undergo whole breast irradiation over 15-25 fractions on consecutive days. Patients then undergo external beam radiation therapy (EBRT) boost over 7 fractions on consecutive days beginning the day following completion of whole breast irradiation. Patients may also undergo magnetic resonance imaging (MRI) and/or mammograms, as well as blood collection throughout the trial.
COHORT B1 and B2: Within 3 months of completing endocrine therapy, patients undergo ultrasound. Patients whose tumor size remains the same, decreases, or does not increase by a certain amount undergo stereotactic ablative body radiation therapy (SABR) over 5 fractions followed by endocrine therapy for 6-12 months. Patients may also undergo additional ultrasounds, MRI and/or mammograms, blood collection, and biopsies throughout the trial.
COHORT C1 and C2: Patients undergo standard of care surgery with lumpectomy and nodal surgery. Patients with results showing no evidence of disease do not receive radiation therapy. Patients may also undergo MRI and/or mammograms, blood collection, and biopsies throughout the trial.
COHORT D: Patients may undergo standard of care surgery and radiation therapy and biopsy pre-treatment and post-surgery.
After completion of study treatment, patients are followed up every 6 months for 5 years and then yearly until 10 years.
Trial PhaseNo phase specified
Trial Typetreatment
Lead OrganizationUT MD Anderson Cancer Center
Principal InvestigatorHenry Mark Kuerer
- Primary ID2016-0046
- Secondary IDsNCI-2016-01929
- ClinicalTrials.gov IDNCT02945579