Multicenter Trial for Eliminating Breast Cancer Surgery or Radiotherapy in Exceptional Responders to Neoadjuvant Systemic Therapy
概览
- 阶段
- 不适用
- 干预措施
- Undergo EBRT
- 疾病 / 适应症
- 未指定
- 发起方
- M.D. Anderson Cancer Center
- 入组人数
- 120
- 试验地点
- 15
- 主要终点
- Ipsilateral breast tumor recurrence-free survival (IBT-RFS)
- 状态
- 招募中
- 最后更新
- 上个月
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: I. Cohort B: 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. 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 standard routine NST, 6 months and one year post-radiotherapy or surgery) among protocol participants with pCR, utilizing circulating tumor cells (CTCs) and circulating tumor-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 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 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. In Cohort B to determine the 3-year rate of tumor control/ progression free survival (PFS). XII. In Cohort C/D to determine whether nanomechanical biomarkers or quantification of stromal and tumor TILS can predict for low risk of local recurrence in exceptional responders who omit radiation therapy. XIII. In Cohorts A/B/C/D: To record 6 mo, 1, 2, 3, 5, 7, and 10 year breast cancer disease-free and overall survival. XIV. In Cohort D: 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. OUTLINE: For Cohorts A, within 12 weeks of completing neoadjuvant systemic therapy, patients 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. For Cohort B, patients will receive 3 months of neoadjuvant endocrine therapy, after which they will receive ablative partial breast irradiation over 5 fractions. Patients will then continue with endocrine therapy. After completion of study treatment, patients are followed up every 6 months for 10 years.
研究者
入排标准
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.
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
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
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
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
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
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
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
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
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
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
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
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
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
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.