NCT06718933招募中1 期
A Prospective, Single-arm, Exploratory, Phase Ib/II Study of SHR-A1811 Combined with Pyrotinib and Bevacizumab in Advanced Breast Cancer with Brain Metastasis.
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- RP2D in phase Ib
研究概览
简要总结
In phase Ib, our study is aimed to evaluate the safety and tolerance of SHR-A1811 combined with pyrotinib in breast cancer with brain metastasis, and confirm the recommended phase 2 dose combined with preliminary results of efficacy.
In phase II, our study is aimed to evaluate the efficacy and safety of SHR-A1811 combined with pyrotinib and bevacizumab at RP2D in breast cancer with brain metastasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •More than 18 years old;
- •ECOG PS Score: 0~2;
- •Patients must have a life expectancy ≥ 3 months;
- •Brian metastasis confirmed by MRI, at least one measurable brain lesion based on RANO-BM with no prior radiotherapy;
- •Mannitol or hormone therapy is allowed to use for brain metastasis before enrolment, but treatment dosage should be stable for one week and not need to be increased;
- •Adequate organ function and marrow function;
- •Has recovered from any AEs (≤ grade 1) related to prior anti-tumour treatments before first dose of study therapy, except: a. alopecia; b. hyperpigmentation;
- •Willing to join in this study, able to provide written informed consent, good compliance and willing to cooperate with follow-up.
排除标准
- •Has leptomeningeal metastasis or cystic metastatic lesions confirmed by MRI or lumbar puncture;
- •Existence of third space fluid (e.g. massive ascites, pleural effusion, pericardial effusion) that is not well controlled by effective methods, e.g. drainage;
- •Has CNS complications with the need for emergency intervention, or brain metastasis with poorly controlled symptoms by hormone or dehydration therapy, such as uncontrollable intracranial hypertension, mental disorder or epilepsy;
- •Prior bevacizumab or EGFR-TKI is allowed, but should meet the following requirements at the same time:
- •No disease progression during prior bevacizumab or EGFR-TKI;
- •More than 3 months from the interruption of bevacizumab or EGFR-TKI to disease progression;
- •Has received whole brain radiotherapy, chemotherapy, surgery within 2 weeks before first dose of study therapy; has received trastuzumab-based therapy or endocrine therapy within one week before first dose of study therapy; has received palliative radiotherapy for bone metastasis within 2 weeks before first dose of study therapy;
- •Has known clinically significant lung disease, that is, moderate-to-severe lung disease which severely affects respiratory function, including but not limited to: idiopathic pulmonary fibrosis, pneumonitis. Prior ≥ grade 3 interstitial lung disease is not allowed to enrolment;
- •Has received full-dose anticoagulants or thrombolytics within 10 days before enrolment, or non-steroid anti-inflammatory drugs with platelet inhibition (except low-dose aspirin (≤325mg qd) for preventive use);
- •Existence of unhealed wound, active gastric ulcer, and other diseases which may cause haemorrhage risk (e.g., prior major operation within 4 weeks before enrolment, prior arterial or venous thrombotic event within one year before enrolment, prior cerebralvascular accident);
- •Has known hereditary haemorrhagic tendency or coagulation disorder;
- •Has joined in other clinical drug trials within 2 weeks before enrolment;
- •Use of other antitumor systemic treatment during the study at the same time, except bisphosphonates for the treatment of bone metastasis or osteoporosis prevention;
- •Other malignancy within prior 5 years unless curatively treated with no evidence of disease for at least recent 3 years, except: curatively treated in situ cancer of the cervix, skin basal cell carcinoma or skin squamous cell carcinoma;
- •Cardiac insufficiency, including but not limited to: congestive heart failure, transmural myocardial infarction, angina which needs drug treatments, clinically significant valvulopathy and high-risk arrhythmia, or QTc abnormity with clinical significance in ECG examination during the screening period (corrected QTc >450 msec [male] or QTc >470 msec [female] under the resting state);
- •Uncontrolled hypertension (under the resting state: systolic pressure >160mmHg or diastolic pressure >100mmHg);
- •Other diseases which may affect study results, including but not limited to: 1) known history of immunodeficiency, including HIV-positive, other acquired or innate immunodeficient disease, or known history of organ transplantation; 2) HBsAg-positive and HBV DNA≥1000 IU/mL, or HCV antibody-positive, or treponema pallidum antibody-positive; 3) hypersensitivity to study therapy or any of its excipients; 4) severe infection requiring antibiotics, antiviral or antifungal treatment;
- •Female patients during the gestation or suckling period, of childbearing potential and pregnancy test-positive, or unwilling to use an effective method of contraception during the whole study;
- •Inability to swallow, intestinal obstruction or existence of other factors affecting medication and absorption;
- •Any other conditions not appropriate for study enrolment in the opinion of the investigator.
研究组 & 干预措施
SHR-A1811+pyrotinib
Experimental
In phase Ib, enrolled subjects will received SHR-A1811 combined with pyrotinib at different doses to confirm RP2D and evaluate the safety and tolerance.
干预措施: SHR-A1811 (Drug)
SHR-A1811+pyrotinib
Experimental
In phase Ib, enrolled subjects will received SHR-A1811 combined with pyrotinib at different doses to confirm RP2D and evaluate the safety and tolerance.
干预措施: Pyrotinib (Drug)
SHR-A1811+pyrotinib+bevacizumab
Experimental
In phase II, enrolled subjects will received SHR-A1811 combined with pyrotinib and bevacizumab to evaluate the efficacy and safety.
干预措施: SHR-A1811 (Drug)
SHR-A1811+pyrotinib+bevacizumab
Experimental
In phase II, enrolled subjects will received SHR-A1811 combined with pyrotinib and bevacizumab to evaluate the efficacy and safety.
干预措施: Bevacizumab (Drug)
SHR-A1811+pyrotinib+bevacizumab
Experimental
In phase II, enrolled subjects will received SHR-A1811 combined with pyrotinib and bevacizumab to evaluate the efficacy and safety.
干预措施: Pyrotinib (Drug)
结局指标
主要结局
RP2D in phase Ib
时间窗: From the enrolment of the first subject, to the end of Cycle 6 completion or disease progression or dose discontinuation due to AE in the last enrolled subject
Recommended phase II dose confirmed by maximum tolerated dose (MTD) and tolerance of subjects.
CNS-ORR by investigator in phase II
时间窗: At baseline, at the time point of every 6 weeks
CNS-ORR is the percentage of evaluable patients with a confirmed investigator-assessed CNS response of CR (complete response) or PR (partial response) per RANO-BM.
次要结局
- Incidence of dose-limiting toxicity (DLT) in phase Ib(At the time point of 21 days from first medication)
- MTD in phase Ib(From the enrolment of the first subject, to the end of Cycle 6 completion or disease progression or dose discontinuation due to AE in the last enrolled subject)
- Incidence and grade of adverse event (AE) and serious adverse event (SAE) in phase Ib(From the time of informed consent provided to 3 months after the last dose of study therapy)
- CNS-ORR per RANO-BM in phase Ib(At baseline, at the time point of every 6 weeks)
- CNS-ORR per RECIST v1.1 in phase Ib(At baseline, at the time point of every 6 weeks)
- CNS-DCR in phase Ib(At baseline, at the time point of every 6 weeks)
- DoR in phase Ib(up to 2 years)
- CNS-ORR per RECIST v1.1 in phase II(At baseline, at the time point of every 6 weeks)
- CNS-DCR in phase II(At baseline, at the time point of every 6 weeks)
- DoR in phase II(up to 2 years)
- PFS in phase II(up to 2 years)
- OS in phase II(up to 2 years)
- Safety in phase II(From the time of informed consent provided to 30 days after the last dose of study therapy)
研究者
Hongxia Wang
Chief physician
Fudan University
研究点 (1)
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