Multicenter Trial for Eliminating Breast Cancer Surgery or Radiotherapy in Exceptional Responders to Neoadjuvant Systemic Therapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 15
- 主要终点
- Ipsilateral breast tumor recurrence-free survival (IBT-RFS)
研究概览
简要总结
This clinical trial studies eliminating surgery and/or radiation therapy in treating breast cancer patients. In HER2 positive and triple negative breast cancers, after systemic therapy, when image-guided biopsy shows no residual cancer, patients then receive standard breast radiotherapy with no surgery. In ER positive/HER2 negative breast cancers, after endocrine therapy and ablative radiotherapy, when image-guided biopsy shows no residual cancer, patients then receive standard endocrine therapy with no surgery. For patients who have HER2 positive and triple negative breast cancers and standard surgery, after systemic therapy, breast radiotherapy is being eliminated when the pathology from surgery shows no residual cancer.
详细描述
PRIMARY OBJECTIVES:
I. Cohort A1 and A2: 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.
II. Cohort B: To determine the pCR rate 6 or 12 months after radiation therapy based on image-guided biopsy.
III. Cohort C: 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.
SECONDARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Cohort A1 and A2
- •Conditions for patient eligibility: 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:
- •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 M
- •HER2 positive (IHC 3+ and or FISH amplified) or triple receptor negative (TN, ER/PR< 10% HER2 negative (IHC 1+ or 2+ FISH non-amplified) receiving any standard routine clinical NST regimen.
- •Patient desires breast conserving therapy.
- •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 [124, 125].
- •Female sex.
- •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.
- •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.
- •Patient understands that the breast lesion size on final breast imaging must be less than or equal to 2 cm prior to the biopsy procedure being performed on study and if the biopsy shows residual carcinoma the patient will be taken off study.
- •Cohort B1 and B2
- •Conditions for patient eligibility: 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:
- •ER and/or PR positive, HER2 negative
- •Clinical stage T1N0M0, unicentric non-lobular breast cancer, no lymphovascular space invasion,
- •At least 40 years of age.
- •Oncotype ≤ 25 if age ≥ 50 years
- •Oncotype 0-20 and tumor size ≤ 1.5cm if age 40-49 years.
- •Patient agrees to take anti-estrogen therapy and is interested in breast conservation
- •Female sex.
- •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.
- •No history of prior radiation to the area of the breast that would require protocol-mandated treatment
- •Conditions for patient eligibility: 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 or following neoadjuvant systemic therapy provided they meet the following eligibility and ineligibility requirements noted below:
- •Pathologically confirmed invasive breast 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.
- •For cohort C 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.
- •Patient desires breast conserving therapy.
- •Age 30 years or older if HER2 positive. Age 50 or older if HER2 negative (triple negative).
- •Female sex.
- •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.
- •Patient must have an initial nodal ultrasound that does not demonstrate suspicious lymph nodes; any suspicious lymph nodes should be biopsied to determine if nodal metastatic disease present.
- •Patient must have no evidence of residual invasive tumor or DCIS on pathologic review of the lumpectomy surgical specimen
- •Patient must have no evidence of metastatic disease or isolated tumor cells involving the lymph nodes on pathologic review of the lymph node surgical specimen. If treatment effect in the nodes is noted on the pathology report, the investigators would generally discourage enrollment on this protocol.
- •Unifocal disease or limited multifocal disease that can be excised in a single lumpectomy specimen
- •Cohort D (MD Anderson Houston patients only)
- •Conditions for patient eligibility: 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.
- •3.5.1 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.
- •3.5.2 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
排除标准
- •Radiologic evidence for a stage T3 or clinical stage T4 breast cancer in Cohort A1/A2/C; radiologic evidence for a stage T2-T3 or clinical stage T4 breast cancer in Cohort B1/B
- •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.
研究组 & 干预措施
Cohort A
- Neoadjuvant chemotherapy therapy
- Biopsy: if no disease remaining - stay on the study and receive radiation (skip breast surgery)
- H&P and Imaging every 6 months
Treatment (whole breast irradiation, EBRT) Within 12 weeks of completing neoadjuvant systemic therapy, patients undergo whole breast irradiation over 15-25 fractions on consecutive days. Patients then undergo EBRT boost over 7 fractions on consecutive days beginning the day following completion of whole breast irradiation.
干预措施: Undergo EBRT (Radiation)
Cohort A
- Neoadjuvant chemotherapy therapy
- Biopsy: if no disease remaining - stay on the study and receive radiation (skip breast surgery)
- H&P and Imaging every 6 months
Treatment (whole breast irradiation, EBRT) Within 12 weeks of completing neoadjuvant systemic therapy, patients undergo whole breast irradiation over 15-25 fractions on consecutive days. Patients then undergo EBRT boost over 7 fractions on consecutive days beginning the day following completion of whole breast irradiation.
干预措施: Laboratory Biomarker Analysis (Other)
Cohort A
- Neoadjuvant chemotherapy therapy
- Biopsy: if no disease remaining - stay on the study and receive radiation (skip breast surgery)
- H&P and Imaging every 6 months
Treatment (whole breast irradiation, EBRT) Within 12 weeks of completing neoadjuvant systemic therapy, patients undergo whole breast irradiation over 15-25 fractions on consecutive days. Patients then undergo EBRT boost over 7 fractions on consecutive days beginning the day following completion of whole breast irradiation.
干预措施: Quality-of-Life Assessment (Other)
Cohort A
- Neoadjuvant chemotherapy therapy
- Biopsy: if no disease remaining - stay on the study and receive radiation (skip breast surgery)
- H&P and Imaging every 6 months
Treatment (whole breast irradiation, EBRT) Within 12 weeks of completing neoadjuvant systemic therapy, patients undergo whole breast irradiation over 15-25 fractions on consecutive days. Patients then undergo EBRT boost over 7 fractions on consecutive days beginning the day following completion of whole breast irradiation.
干预措施: Partial Breast Irradiation (Radiation)
Cohort B
• Neoadjuvant endocrine therapy for 3 months
Cohort B Radiation:
Treatment (Stereotactic ablative radiotherapy -SABR) Following 3-6 months of endocrine therapy, if less than 25% tumor increase, patients undergo SABR irradiation over 5 fractions
- Continued endocrine therapy for total of 5 years Biopsy 6-12months after radiation: if negative - additional endocrine therapy under the guidance of medical oncologist (skip breast surgery)
- H&P and Imaging every 6 months
干预措施: Undergo EBRT (Radiation)
Cohort B
• Neoadjuvant endocrine therapy for 3 months
Cohort B Radiation:
Treatment (Stereotactic ablative radiotherapy -SABR) Following 3-6 months of endocrine therapy, if less than 25% tumor increase, patients undergo SABR irradiation over 5 fractions
- Continued endocrine therapy for total of 5 years Biopsy 6-12months after radiation: if negative - additional endocrine therapy under the guidance of medical oncologist (skip breast surgery)
- H&P and Imaging every 6 months
干预措施: Laboratory Biomarker Analysis (Other)
Cohort B
• Neoadjuvant endocrine therapy for 3 months
Cohort B Radiation:
Treatment (Stereotactic ablative radiotherapy -SABR) Following 3-6 months of endocrine therapy, if less than 25% tumor increase, patients undergo SABR irradiation over 5 fractions
- Continued endocrine therapy for total of 5 years Biopsy 6-12months after radiation: if negative - additional endocrine therapy under the guidance of medical oncologist (skip breast surgery)
- H&P and Imaging every 6 months
干预措施: Quality-of-Life Assessment (Other)
Cohort B
• Neoadjuvant endocrine therapy for 3 months
Cohort B Radiation:
Treatment (Stereotactic ablative radiotherapy -SABR) Following 3-6 months of endocrine therapy, if less than 25% tumor increase, patients undergo SABR irradiation over 5 fractions
- Continued endocrine therapy for total of 5 years Biopsy 6-12months after radiation: if negative - additional endocrine therapy under the guidance of medical oncologist (skip breast surgery)
- H&P and Imaging every 6 months
干预措施: Partial Breast Irradiation (Radiation)
Cohort C
- Optional biopsy for nanomechanical biomarker assessment
- Neoadjuvant chemotherapy therapy
- Surgery (& optional biopsy nanomechanical biomarker assessment): if no disease remaining - stay on the study and skip radiation
- H&P and Imaging every 6 months
干预措施: Quality-of-Life Assessment (Other)
Cohort C
- Optional biopsy for nanomechanical biomarker assessment
- Neoadjuvant chemotherapy therapy
- Surgery (& optional biopsy nanomechanical biomarker assessment): if no disease remaining - stay on the study and skip radiation
- H&P and Imaging every 6 months
干预措施: Questionnaire Administration (Other)
Cohort D
- Optional biopsy for nanomechanical biomarker assessment
- Chart review every year after surgery for 5 years
- Eligible patients who have undergone the optional biopsy may later move to Cohort A or C if they meet all eligibility requirements and desire radiation omission.
干预措施: Questionnaire Administration (Other)
Cohort B
• Neoadjuvant endocrine therapy for 3 months
Cohort B Radiation:
Treatment (Stereotactic ablative radiotherapy -SABR) Following 3-6 months of endocrine therapy, if less than 25% tumor increase, patients undergo SABR irradiation over 5 fractions
- Continued endocrine therapy for total of 5 years Biopsy 6-12months after radiation: if negative - additional endocrine therapy under the guidance of medical oncologist (skip breast surgery)
- H&P and Imaging every 6 months
干预措施: Questionnaire Administration (Other)
Cohort C
- Optional biopsy for nanomechanical biomarker assessment
- Neoadjuvant chemotherapy therapy
- Surgery (& optional biopsy nanomechanical biomarker assessment): if no disease remaining - stay on the study and skip radiation
- H&P and Imaging every 6 months
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Ipsilateral breast tumor recurrence-free survival (IBT-RFS)
时间窗: From confirmation of pathologic complete response (pCR) to the time of ipsilateral breast tumor recurrence or death, whichever occurs first or the time of last contact, assessed for up to 10 years
Will monitor IBT-RFS using the method of Thall et al. Will be estimated using the Kaplan-Meier method log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.
Overall survival
时间窗: Up to 10 years
Will be estimated using the Kaplan-Meier method log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.
次要结局
未报告次要终点