Avidination for Radionuclide THerapy (A.R.THE.) in Nonpalpable Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Safety of avidin-biotin-Dota-90Y
研究概览
简要总结
This is an interventional, open-label, non comparative phase 2 trial enrolling patients with nonpalpable breast cancer
详细描述
Nonpalpable breast lesions (NPBLs) represent approximately 30% of the overall tumoral breast lesions undergoing surgery. The Vacuum-Assisted Breast Biopsy (VABB) is a device for needle breast biopsy usefully applied in NPBL. The procedure is highly effective for the diagnosis of NPBLs, with minimal negative effects. The specimen volume obtained through this procedure is great enough to replace the diagnostic surgical excisional biopsy and frozen section intraoperative examination. Biopsies obtained through this method sometimes allow the complete excision of the lesion, representing a valid alternative to the excisional biopsy in case of benign lesion less than 15 mm in size.
After VABB procedure about 10-30% of patients have a complete removal of the neoplastic lesion. About 30% of patients are disease free after surgery because the lesion has been totally removed through diagnostic VABB procedure. The rationale of this project is to treat residual microscopic disease through a radionuclide therapy. Our idea is to administer, following VABB procedure, an avidin-biotin-DOTA-90Y (where DOTA stands for 1,4,7,10-tetra-azacyclododecane-N,N',N'',N'''-tetraacetic acid and Y stands for yttrium) compound into the lesion site in order to eliminate residual tumour cells. The ARTHE approach should increase the rate of disease free cases after excisional biopsy.
The primary objective of this open-label phase I trial is to evaluate the safety of avidin-biotin-DOTA-90Y combination in patients with nonpalpable breast cancer undergoing Vacuum-Assisted- Breast- Biopsy (VABB). The co-primary objective is the evaluation of the preliminary anti-tumor activity of the treatment. The secondary objective is to evaluate the dosimetry and biodistribution of avidin-biotin-DOTA-90Y after loco-regional injection under ultrasound guidance.
ARTHE procedure consists of the ultrasound guided injection of Avidin into the breast tissue corresponding to VABB site followed by an injection of Biotin-DOTA-90Y. The injected Biotin-DOTA-90Y will be in a range 28-126 MBq (megabecquerel) (0.2- 0.3 mL, specific activity of 3.7 GBq/mg) (gigabequerel/milligrams). The investigators will inject 6-10 mg of avidin in a volume of 0.3-0.5 mL, followed by biotin-DOTA-90Y immediately after avidin injection.
The hypothesis that a treatment with avidin-biotin-DOTA-90Y is able to destroy residual cancer cells after VABB will be verified by surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients must have diagnosis of occult breast cancer on the basis of mammography (BIRADS's score 4 - 5)/ultrasound (SCORE 4-5).
- •Pathological diagnosis of in situ or infiltrating breast carcinoma (any histotype)
- •Tumor size >5 and ≤15 mm (at least 13 mm from the skin surface)
- •Female, 18≤age≤
- •ECOG (Eastern Cooperative Oncology Group) performance status <2
- •Patients scheduled to receive conservative surgical treatment
- •The effects of investigational medicinal product (IMP) on the developing human fetus are unknown. For this reason and because IMP in this trial is known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion. See Appendix E for the "Recommendations related to contraception and pregnancy testing in clinical trials". Should a woman become pregnant or suspect she is pregnant, she should inform her treating physician immediately.
- •Participant is willing and able to give informed consent for participation in the study.
排除标准
- •Histotype different from carcinoma
- •Paget carcinoma
- •Lesions located near to axilla region or skin <13 mm
- •Ongoing pregnancy or breastfeeding
- •Previous treatment with avidin
- •Referred allergy to eggs or latex
- •Patients with metastases should be excluded from this clinical trial.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patients with previous radiotherapy and/or operation on the same breast, with diffuse microcalcifications will be excluded.
- •Patients with known BRCA (BReast CAncer gene), PALB2 (Partner and Localizer of BRCA2) and CHECK2 (Checkpoint Kinase 2) mutations, grade 3 risk profile or indication to perform a test for germline mutations based on disease characteristics
- •Multifocal tumors are not eligible for the study.
- •History of malignancy within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS (overall survival) rate >90%).
研究组 & 干预措施
Avidin-biotin-Dota-90Y
The total planned enrollment for this study is up to approximately 52 patients for Part 1 (dose-escalation) and Part 2 (dose expansion). Up to 18 patients will be enrolled in Part 1 (depending on dose-escalation) and 40 patients in dose expansion in Part 2. The 6 patients evaluated for dosimetry in Part 1 will also be evaluated in part 2.
干预措施: Avidin-biotin-Dota-90Y (Drug)
结局指标
主要结局
Safety of avidin-biotin-Dota-90Y
时间窗: 4-7 weeks
The primary endpoint is the systemic toxicity evaluated according to NCI-CTCAE (The U.S. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events) Version 5.0
Anti-tumor activity of avidin-biotin-Dota-90Y
时间窗: 4-7 weeks
The co-primary endpoint is the evaluation of the complete pathological response rate, defined as the absence of residual invasive and in situ cancer or DCIS (ductal carcinoma in situ), on hematoxylin and eosin evaluation of the complete resected breast specimen and of all sampled regional lymph nodes (i.e., ypT0 ypN0 in the current AJCC staging system).
次要结局
- Dose-response(48-72 hours after injection)
- Biodistribution(1-3 hours after injection)