Study of SHR-A1811 Combined with Pyrotinib and Bevacizumab in Advanced Breast Cancer with Brain Metastasis
Status and phase
Conditions
Treatments
Details and patient eligibility
About
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.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
- 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.
Exclusion criteria
-
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.
Trial design
Primary purpose
Allocation
Interventional model
Masking
74 participants in 2 patient groups
Trial contacts and locations
Loading...
Central trial contact
Ting Li, Associate chief physician; Hongxia Wang, Chief physician
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal