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Brain metastases occur in 30-50% of patients with metastatic HER2-positive breast cancer. Pyrotinib is an irreversible pan-ErbB receptor tyrosine kinase inhibitor (TKI) with activity against epidermal growth factor receptor (EGFR)/HER1, HER2, and HER4. This study consists of two parts. In a phase Ib part, investigators will explore the safety and tolerance of Pyrotinib Plus Capecitabine combined with brain radiotherapy. After completing the phase Ib part, investigators will review the data and decide whether this patient is included in before the start of a phase II part. In the phase II part, investigators will evaluate the efficacy of Pyrotinib Plus Capecitabine combined with brain radiotherapy in patients with HER2 positive breast cancer patients with brain metastases.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pyrotinib Plus Capecitabine combined with brain radiotherapy | Experimental | Fractionated stereotactic radiotherapy(FSRT) or whole brain radiation therapy (WBRT) Drug: Pyrotinib combined with capecitabine pyrotinib 400 mg once daily; Capecitabine 1000 mg/m2 per day on day 1 through 14, every 21 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pyrotinib Plus Capecitabine combined with brain radiotherapy | Other | Drug combined with radiation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Assess safety and tolerability of Pyrotinib Plus Capecitabine combined with brain radiotherapy(Phase Ib part) | AEs will be assessed according to CTCAE version 4.03. (1)Initially 3 patients will be accrued and treated with combined therapy as a lead-in safety phase. Enrollment of the study will not proceed if patients in the safety lead-in phase experience unacceptable toxicities including neurologic, hematologic and other dose limiting toxicities.(see protocol) (b)If one of initially 3 patients has experienced unacceptable toxicities, 3 more patients will be accrued . (3)If two or more patients are unable to complete radiation therapy (RT) due to toxicity related to Pyrotinib Plus Capecitabine combined with brain radiotherapy, accrual will be suspended and the study will be stopped. (4) If 3+3 patients are able to complete the treatment without unacceptable toxicities, 6 more patients will be accrued in Ib part. | 8 weeks |
| Intracranial local tumor control rate (Phase II part) | All intracranial progression | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Intracranial local tumor control rate with FSRT or WBRT | Intracranial local tumor control rate | 2 years |
| Intracranial Progression-Free Survival (PFS) | Time from the date of radiotherapy to the investigator-determined date of progression (determined by RANO) or death due to any cause, whichever occurs first |
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Inclusion Criteria:
Pathologically confirmed HER2 positive advanced breast cancer
Age>18 years. brain metastases confirmed by enhanced brain MRI
KPS≥70
Life expectancy of more than 12 weeks
Prior therapy of oral dexamethasone not exceeding 16mg/d
Time interval from prior therapy was more than 2 weeks, and evaluation of adverse events is no more than grade 1.
Maximum diameter of intracranial metastases is less than 3cm measured by enhanced brain MRI(2-3mm)
Prior endocrine therapy were allowed
Anti-Her2 targeted treatment were allowed
Screening laboratory values must meet the following criteria( and should be obtained within 28 days prior to registration):
Signed the informed consent form prior to patient entry
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Xiaoli Yu, MD PhD | Fudan University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Shanghai | 200032 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39024777 | Derived | Dai L, Gao T, Guo R, Chen Y, Wang J, Zhou S, Tang Y, Chen D, Huang S. Efficacy and safety of pyrotinib-based regimens in HER2 positive metastatic breast cancer: A retrospective real-world data study. Neoplasia. 2024 Oct;56:101029. doi: 10.1016/j.neo.2024.101029. Epub 2024 Jul 17. | |
| 38175627 | Derived | Yang Z, Meng J, Mei X, Mo M, Xiao Q, Han X, Zhang L, Shi W, Chen X, Ma J, Palmer J, Shao Z, Zhang Z, Yu X, Guo X. Brain Radiotherapy With Pyrotinib and Capecitabine in Patients With ERBB2-Positive Advanced Breast Cancer and Brain Metastases: A Nonrandomized Phase 2 Trial. JAMA Oncol. 2024 Mar 1;10(3):335-341. doi: 10.1001/jamaoncol.2023.5791. |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| C000622954 | pyrotinib |
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| 2 years |
| Extracranial Progression-Free Survival (PFS) | 2 years |
| OS (overall survival) | 3 years |
| D017437 |
| Skin and Connective Tissue Diseases |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |