Study of SHR-A1811 Combined With Pyrotinib and Bevacizumab in Advanced Breast Cancer With Brain Metastasis
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorFudan University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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;
No disease progression during prior bevacizumab or EGFR-TKI;
Trial design
Design model
Sequential
Treatments tested in this trial
SHR-A1811
DrugADC
Bevacizumab
Drugbevacizumab biosimilar
Pyrotinib
Druganti-HER2 inhibitor
Treatment groups
74 Participants
are divided into 2 treatment groupsGroup A: SHR-A1811+pyrotinibExperimental treatment 2 interventions
Group B: SHR-A1811+pyrotinib+bevacizumabExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
RP2D in phase Ib
Recommended phase II dose confirmed by maximum tolerated dose (MTD) and tolerance of subjects.
Time frame
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 subject2
CNS-ORR by investigator in phase II
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.
Time frame
At baseline, at the time point of every 6 weeksSecondary outcomes
1
Incidence of dose-limiting toxicity (DLT) in phase Ib
Incidence of DLT
Time frame
At the time point of 21 days from first medication2
MTD in phase Ib
MTD is the highest dose that does not cause any adverse effects as follows: a) 1 subject experienced the treatment-related serious adverse effects that could endanger the life, cause permanent disability or death; b) 2 of 3 subjects experienced DLTs; c) 1 of the first 3 subjects experienced DLTs, and 1 of the additional 3 subjects at the same dose level experienced DLTs again.
Time frame
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 subject3
Incidence and grade of adverse event (AE) and serious adverse event (SAE) in phase Ib
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. An SAE is defined as any medical event that results in any of the following outcomes: requires inpatient hospitalization or prolongation of existing hospitalization, disability or incapacity, affects ability to work, a life-threatening adverse event or death, a congenital anomaly.
Time frame
From the time of informed consent provided to 3 months after the last dose of study therapy4
CNS-ORR per RANO-BM in phase Ib
CNS-ORR is the percentage of evaluable patients with a confirmed CNS response of CR (complete response) or PR (partial response) per RANO-BM.
Time frame
At baseline, at the time point of every 6 weeksSponsors and contacts
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Source ClinicalTrials.gov