Basket Study for Oligo-metastatic Breast Cancer Part 1: Trastuzumab-deruxtecan for HER2-positive Oligo-metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Complete radiologic response
研究概览
简要总结
The study will include patients with HER2-positive breast cancer and 1- 3 distant metastatic lesions, all amenable for curative intervention. Patients will be stratified by prior therapy and ER expression. In the initial baskets patients with be treated with trastuzumab-deruxtecan.
Patients are treated with T-DXd 5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. The first 8 cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment.
The proposed M22BOL trial is based on an important knowledge gap for regarding breast cancer patients with 'oligo-metastatic' disease who are usually not included in clinical trials for patients with metastatic disease since loco-regional treatments (radiation, surgery) with curative intent is not allowed in clinical trials for metastatic breast cancer. Moreover, neo-adjuvant trial protocols for early breast cancer exclude patients with distant metastases that can be treated with curative intent. This basket trial evaluates T-DXd for oligo-metastatic breast cancer with the goal to induce deep responses and subsequently long-lasting disease remissions and potentially cure.
详细描述
The study will include patients with HER2-positive breast cancer and 1- 3 distant metastatic lesions, all amenable for curative intervention. Patients will be stratified by prior therapy and ER expression. Given the basket-design of this trial other baskets for oligo-metastatic breast cancer can be added, such as but not limited to other breast cancer subtypes or with other promising drugs.
Baskets for de novo oligo-metastatic disease I. ER+/HER2+ II. ER-/HER2+ Baskets for oligo-metastatic disease after prior chemo/anti-HER2 therapy for primary disease III. ER+/HER2+ IV. ER-/HER2+
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologic proof of infiltrating HER2-positive breast cancer (as determined by IHC 3+ and/or amplification by ISH)[8]
- •Histologic or cytologic proof of breast cancer metastases (at least one lesion)
- •Histologic determination of level of ER-expression
- •Oligo-metastatic disease as determined by standard of care diagnostics. The number of total individual distant metastases is limited to five, either in one organ or in 2-5 organ systems. Clustered lymph nodes that can be irradiated with curative intent in a single field are defined as single lesion. Pleuritis carcinomatosa, miliary spread of metastases (even within one organ), or peritoneal spread of metastases rules out oligo-metastatic disease and is not allowed. Initial staging by PET-CT (whole body) and MRI of breast and brain are mandatory, as is MRI liver or spine and pelvis in case of liver or bone metastases respectively.
- •In case of recurrent disease, a disease-free interval of 24 months.
- •Measurable disease according to RECIST1.1
- •Patients must be at least 18 years of age and be able to give written informed consent and comply with study procedures.
- •World Health Organization (WHO) performance status 0 or 1
排除标准
- •prior line of therapy for metastatic disease. Exceptions are endocrine therapy or radiation considered to be part of the curative treatment, within 3 months before enrolment
- •leptomeningeal disease or central nervous metastases
- •clinically relevant obstruction or compression of spinal cord, central nervous, gastro-intestinal or cardiovascular system, that cannot be alleviated before start of treatment.
- •other malignancy, unless treated with curative intention and a long-term survival probability of >95%, including in-situ or pre-malignant lesions.
研究组 & 干预措施
Trastuzumab-deruxtecan
5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. The first 8 cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment.
干预措施: Trastuzumab deruxtecan (Drug)
结局指标
主要结局
Complete radiologic response
时间窗: up to one year after start treatment
Number of patients to achieve radiologic response as defined by RECIST 11 with clearnace of ctDNA
次要结局
- Number of patients free of progression(assessed up to 10 years)
- Overall Survival(assessed up to 10 years)
- Number of patients with pathological complete response(assessed immediately after surgery)
- Number of patients with metabolic response(assessed up to 10 years)
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)(assessed up to 30 days after last treatment)