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Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This study is a randomized,open-label,multi-center,active-controlled, parallel design study of the combination of pyrotinib and capecitabine versus Lapatinib plus capecitabine in HER2+ MBC patients, who have prior received taxane and trastuzumab.Patients will be randomized in a 1:1 ratio to one of the following treatment arms.Arm A: pyrotinib (400 mg once daily) + capecitabine (1000 mg/m^2 twice daily),Arm B: Lapatinib (1250 mg once daily) + capecitabine (1000 mg/m^2 twice daily).Patients will receive either arm of therapy until disease progression, unacceptable toxicity, or withdrawalof consent.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pyrotinib Plus Capecitabine | Experimental |
| |
| Lapatinib Plus Capecitabine | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pyrotinib Plus Capecitabine | Drug | pyrotinib(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/ m^2 BID) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival(PFS) | From infromed consent to progression or death | Estimated 10 months |
| Measure | Description | Time Frame |
|---|---|---|
| Safety: AE | AE | AE recorded from infromed consent to 28 days after treatment completion |
| Overall Survival (OS) | From infromed consent to death |
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Inclusion Criteria:
Aged ≥18 and ≤70 years.
ECOG performance status of 0 to 1.
Life expectancy of more than 12 weeks.
According to RECIST 1.1, at least one measurable lesion exists
Histologically or cytologic confirmed HER2 positive metastatic breast cancer.
Prior treatment with trastuzumab (≥2 cycles in metastatic setting, or
≥3 months in adjuvant/neoadjuvant setting) and Taxane(≥2 cycles in any setting or untill unendurable AE or progression during treatment).
Previously reveived ≤2 chemotherapy regimens in metastasis setting;
Required laboratory values including following parameters:
ANC: ≥ 1.5 x 10^9/L; Platelet count: ≥ 90 x 10^9/L; Hemoglobin: ≥ 90 g/L; Total bilirubin: ≤ 1.5 x upper limit of normal (ULN); ALT and AST: ≤ 2 x ULN(patients with liver metastases: ≤5 x ULN); BUN and Creatinine:
≤ 1x ULN;CCR≥50 mL/min;LVEF: ≥ 50%;QTcF: < 450 ms (male),< 470 ms(female);
Signed informed consent.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Institute and Hospital,Chinese Academy of Medical Science | Beijing | Beijing Municipality | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36135045 | Derived | Bao Y, Zhang Z, He X, Cai L, Wang X, Li X. Cost-Effectiveness of Pyrotinib Plus Capecitabine versus Lapatinib Plus Capecitabine for the Treatment of HER2-Positive Metastatic Breast Cancer in China: A Scenario Analysis of Health Insurance Coverage. Curr Oncol. 2022 Aug 23;29(9):6053-6067. doi: 10.3390/curroncol29090476. | |
| 33581774 |
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| Lapatinib Plus Capecitabine | Drug | Lapatinib (1250 mg once daily)+ capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID) |
|
| Estimated 30 months |
| Objective Response Rate (ORR) | CR+PR | Estimated 10 months |
| Time to Progression (TTP) | From infromed consent to progression | Estimated 10 months |
| Duration of Response (DOR) | CR+PR+SD | Estimated 10 months |
| Clinical Benefit rate (CBR) | CR+PR+SD≥24 weeks | Estimated 10 months |
| Xu B, Yan M, Ma F, Hu X, Feng J, Ouyang Q, Tong Z, Li H, Zhang Q, Sun T, Wang X, Yin Y, Cheng Y, Li W, Gu Y, Chen Q, Liu J, Cheng J, Geng C, Qin S, Wang S, Lu J, Shen K, Liu Q, Wang X, Wang H, Luo T, Yang J, Wu Y, Yu Z, Zhu X, Chen C, Zou J; PHOEBE Investigators. Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Mar;22(3):351-360. doi: 10.1016/S1470-2045(20)30702-6. Epub 2021 Feb 11. |
| ID | Term |
|---|---|
| C000622954 | pyrotinib |
| D000069287 | Capecitabine |
| D000077341 | Lapatinib |
| ID | Term |
|---|---|
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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