Evaluating the Use of Stereotactic Radiation Therapy Prior to Neoadjuvant Chemotherapy for High-risk Breast Carcinoma (a SIGNAL Series Clinical Trial): Three Fraction Radiation to Induce Immuno-Oncologic Response (TRIO Trial)
概览
- 阶段
- 不适用
- 干预措施
- Neoadjuvant radiotherapy
- 疾病 / 适应症
- High-Risk Cancer
- 发起方
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Pathologic complete response
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
Patients with high risk breast cancers (any locally advanced breast cancer patient defined as Stages IIB-III [excluding inflammatory breast cancer] with stage IIA being eligible for triple negative and HER2-positive breast cancers) will receive neoadjuvant radiation to any portion of their tumour in three fractions in order to act as an immune primer. Radiation will be delivered to a portion of the tumour in three fractions. The patient will be positioned prone as per the SIGNAL 2.0 protocol. The patient will then go on to standard of care treatment (neoadjuvant chemotherapy and surgery) followed by whole-breast radiation as needed. Pathologic complete response will be the primary outcome. Immune markers will also be evaluated.
详细描述
Patients eligible for neoadjuvant chemotherapy for locally advanced stage III (non-inflammatory) breast cancer or stage IIb (triple negative or Her2+) breast cancers will be approached to participate in this single arm trial. Patients with staging investigations ruling out distant disease will be approached to participate and will undergo pre-treatment image guided core biopsy and blood samples for molecular correlative studies, followed by hypofractionated radiation (delivered prone) to entire tumor with dose constraints to skin, critical organs and contralateral breast, plus a 0.5 cm PTV. As much of the tumor that can receive planned dose of 8 Gy per fraction x 3 fractions every second day, with fall off dose to 4 Gy per fraction x 3 fractions for PTV margin. Two weeks following completion of radiation, patients will undergo a second image guided core needle biopsy of tumor and blood sample. They will then begin standard neoadjuvant chemotherapy (anthracycline and taxane based), followed by a third tissue biopsy under image guidance of any residual tumor and blood sample and then standard surgery (breast conserving or lumpectomy). This will be followed by standard whole breast radiation (50 Gy in 25 fractions). Herceptin therapy and hormonal therapy will be administered as per clinical standard when indicated. Primary outcome will be measured as pathological complete response to treatment, and secondary outcomes will include toxicity, immune markers (tumor infiltrating lymphocytes, PD-1 and PD-L1 up-regulation and changes to the circulating lymphocyte counts.
研究者
入排标准
入选标准
- •Any biopsy-proven locally advanced breast cancer patient defined as Stages IIB-III (excluding inflammatory breast cancer). Stage IIA is eligible for triple negative and HER2-positive breast cancers
- •Invasive mammary carcinoma of any subtype excluding lobular, sarcomatous, or metaplastic subtypes, or with lobular features
- •Plan to be treated with neoadjuvant chemotherapy
- •Able to fit in/have MRI
- •18 years of age or older
- •Able to tolerate core needle biopsies
- •Able to provide informed consent
- •No evidence of metastatic disease
排除标准
- •Any serious medical comorbidities or other contraindications to radiotherapy, chemotherapy, or surgery
- •Prior treatment for current breast cancer
- •Previous radiation therapy to the same breast
- •Inflammatory breast carcinoma
- •Invasive lobular carcinoma or invasive mammary carcinoma with lobular, sarcomatous, or metaplastic subtypes, or with lobular features
- •Recurrent breast cancer
- •Bilateral breast cancer
- •Evidence of distant metastatic disease
- •Collagen vascular disease (particularly lupus, scleroderma, dermatomyositis, psoriatic arthritis)
- •Any other malignancy at any site (except non-melanomatous skin cancer) \<5 years prior to study enrollment
研究组 & 干预措施
Neoadjuvant radiotherapy
3 doses of stereotactic radiotherapy administered prior to neoadjuvant chemotherapy in high-risk breast cancers.
干预措施: Neoadjuvant radiotherapy
结局指标
主要结局
Pathologic complete response
时间窗: Measured at time of surgery, typically 6 months after enrollment in trial.
Pathologic complete response rates after neoadjuvant radiotherapy and chemotherapy will be evaluated.
次要结局
- Response rates in the primary post chemotherapy by imaging(Measured after neoadjuvant radiation and chemotherapy has been completed, prior to surgery, typically 6 months after enrollment in trial.)
- Response rates in the axillary nodes post chemotherapy by imaging and pathology(Measured after neoadjuvant radiation and chemotherapy has been completed, prior to surgery (imaging) and at time of surgery, typically 6 months after enrollment in trial.)
- Immune priming(Measured 14-20 days after the last dose of neoadjuvant radiation, prior to the start of neoadjuvant chemotherapy.)
- Radiation toxicity(Measured at study enrollment, at first surgical follow-up post-surgery, 6 months post surgery, and 1 year post surgery.)
- Surgical wound healing and the overall complication rate.(Measured at the first surgical follow-up post-surgery, 6 months post surgery, and 1 year post surgery.)
- Local recurrence rates(Disease status will be evaluated at routine patient follow-up appointments, including yearly mammography. Will be reported at year 3.)
- Ability of imaging to predict patient response to radiotherapy.(Pre-treatment imaging to be done after study enrollment (baseline) and 14-20 days after the last dose of neoadjuvant radiation has been delivered.)
- Ability of imaging markers to predict response to radiotherapy(Pre-treatment imaging to be done after study enrollment (baseline measurements) and 14-20 days after the last dose of neoadjuvant radiation has been delivered.)
- Ability to predict pathological response to treatment based on tumour genetics(Tissue samples for analysis will be taken 14-20 days after completion of neoadjuvant radiation, prior to the start of neoadjuvant chemotherapy and will be compared with tissue taken prior to the start of neoadjuvant radiation.)