Comparing Sequential Neoadjuvant Treatment Including Chemotherapy and Accelerated Radiation Focused to the Tumor Bed vs Neoadjuvant Chemotherapy Alone, for Triple Negative Locally Advanced Breast Cancers and Luminal B Proliferating, Inaccessible to a Conservative Surgery the Outset
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 362
- 试验地点
- 6
- 主要终点
- PCR rates
研究概览
简要总结
In the NeoAPBI 01 trial, the objective is to demonstrate the efficacy of combined APBI and CT administered sequentially in patients with intermediate ad high risk BC. The hypothesis is that combined PST-sequential APBI may increase the rate of pCR, breast conservation and survival without additional toxicity, as seen with WBI
详细描述
Phase I:
The total APBI dose is set to level I at 20 Gy (in 10 fractions over 5 days; n=5) and then level II at 24 Gy (in 12 fractions over 6 days) delivered to the tumor using two fractions/day of 2 Gy spaced by at least 6 hours. The biological effective dose (BED) is 32 Gy and 47 Gy for alpha/beta of 10 and 3.5, respectively. As compared to the standard fractionation of 2 Gy/fraction the BED is 26.8 Gy and 30 Gy for the 2 values of alpha/beta.
In case of the impossibility to deliver two fractions/day, patients should be treated using a single fraction of 3.125 Gy/day up to 8 fractions (total dose of 25 Gy). The BED is 32.8 Gy and 47.3 Gy for alpha/beta of 10 and 3.5, respectively. As compared to the standard fractionation of 2 Gy/fraction the BED is 27.3 Gy and 30.1 Gy for the 2 values of alpha/beta.
In both schemes, 95% of the prescribed dose should be delivered in at least 90% of the PTV.
All patients who undergo BCS after the end of PST-APBI will receive postoperative WBI (+/- nodal areas) delivering a total dose of 45-50 Gy using standard fractionation (1.8 or 2 Gy) or hypofractionated schedules using > 15 fractions in 3 weeks. Technique and boost delivery will be left at the investigator's discretion and local policy. Patients who had TM should also receive PMRT if indicated delivering 45-50.4 Gy using standard fractionation (1.8 or 2 Gy). If the patient did not complete a full course of PST prior to surgery, CT will be given prior to or immediately following postoperative RT depending on the institutional protocol. Other post-operative treatments will be at the investigator's discretion. Adjuvant hormonal treatment will be administered to HR+ patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients ≥ 18 years of age
- •Histologically confirmed invasive carcinoma of the breast
- •Patient who desires breast conservation
- •Tumor stage T1N1, T2-3 N0-1
- •Operable BC for which an indication for CT is determined, including T1N1 and high risk T2-3 N0-1 tumors.
- •Lobular and/or ductal invasive carcinoma
- •Confirmation by imaging (standard +/- MRI) of unicentric and unilateral disease
- •Luminal B (defined by hormone receptor positive and grade II-III (if available from core biopsy) and Ki67 ≥ 15% or by genomic analysis) and TNG subtypes
- •HER2 negative
- •No distant metastases
- •No contraindication for PST with anthracycline and/or taxane based regimens
- •Patients with no psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator with the aid of written information.
排除标准
- •Patients considered too frail for CT whatever their age.
- •Breast cancer clinical grade T4 and /or with major nodal involvement N2 (clinically, US, MRI or PET-CT).
- •Lumpectomy is considered to be possible with an anticipated favourable cosmetic outcome considering the tumor size/breast size
- •Multicentricity that would not allow BCS as confirmed by breast imaging
- •Uni or bilateral inflammatory (T4d) BC
- •Metastatic disease
- •Other histology types: ciribriform or tubular or mucinous or epideroid carcinomas
- •Her2 positive
- •No signed consent to participate in the study
- •Previous malignancy (except non melanoma skin cancer, thyroid carcinoma, non-invasive cancers outside the breast and patients with previous cancer in remission since more > 5 years)
- •Patients with psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule
- •Patients unwilling or unable to comply with the protocol (especially necessity to undergo breast surgery despite clinical complete response)
- •Patients who have received any other investigational drugs within 30 days prior to the screening visit
- •Pregnancy
- •Active connective tissue disease involving the skin
- •Patients with other concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study .
研究组 & 干预措施
Arm A
6-8 cycles of Primary systemic therapy using anthracycline and/or taxane based regimens, according to their physician's preference and center policy
干预措施: Chemotherapy (Drug)
Arm B
The patients will receive 3D conformal or other modality (eg IMRT, VMAT) APBI during their PST sequence. APBI will be planned sequentially between the Primary systemic therapy cycles, 2 weeks after the 3rd/6 or the 4th/8 cycle of PST.
干预措施: Accelerated partial breast irradiation (Radiation)
Arm B
The patients will receive 3D conformal or other modality (eg IMRT, VMAT) APBI during their PST sequence. APBI will be planned sequentially between the Primary systemic therapy cycles, 2 weeks after the 3rd/6 or the 4th/8 cycle of PST.
干预措施: Chemotherapy (Drug)
结局指标
主要结局
PCR rates
时间窗: At the end of chemotherapy: up to 21 weeks
Pathological complete response (pCR), defined by the absence of invasive residual primary tumor in the breast and lymph node.The primary objective of this study is to compare pCR rates after Primary Systemic Therapy (PST) plus APBI versus PST alone in patients with luminal and TNG BC prior to BC surgery.
次要结局
- PCR 2(At the end of chemotherapy: up to 21 weeks)
- Breast conservation rate(Intraoperative)
- Acute and late toxicities(At the end of chemotherapy and after surgery and after radiotherapy: up to 30 weeks)