Patient case: 64-year-old male with gastric cancer; genetic feature: ERBB2 amplification

Clinical trial: A Study of Pyrotinib Plus Capecitabine in Patients With Brain Metastases From HER2-positive Metastatic Breast Cancer

Summary: Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors.This study is a single-arm, prospective, open label clinical study of pyrotinib plus capecitabine as the Therapy of brain metastases from HER2-positive metastatic breast cancer.

Detailed description: Brain metastases occur in 30-50% of patients with metastatic HER2-positive breast cancer. In the case of solitary brain metastases, surgery or stereotactic radiosurgery are the preferred therapeutic approaches.Chemotherapy is used after further progression of disease but it has limited effectiveness. In HER2-positive tumours, trastuzumab therapy has been postulated to be associated with an increased risk of development of brain metastases.Thus new therapeutic options are urgently needed to improve patients'outcome. Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. We designed the study to explore the possibility of pyrotinib plus capecitabine for brain metastases from HER2-positive metastatic breast cancer.

Eligibility: Inclusion Criteria:
  1. Aged ＞18 years.
  2. ECOG performance status ≤2.
  3. Histologically or cytologic confirmed HER2 positive advanced breast cancer.
  4. MRI confirmed brain metastases. According to RECIST 1.1, at least one measurable lesion exists.
  5. No limit of previous chemotherapy lines.
  6. Previously have not reveived capecitabine or disease progression of capecitabine after 6 months, or progression of capecitabine adjuvant therapy after one year;
  7. Life expectancy of more than 3 months.
  8. Required laboratory values including following parameters: ANC: ≥ 1.5 x 10^9/L;Platelet count: ≥ 100 x 10^9/L;Hemoglobin: ≥ 9.0 g/dL;Total bilirubin: ≤ 1.5 x upper limit of normal (ULN);ALT and AST: ≤ 1.5 x ULN (or ≤ 5×ULN in patients with liver metastases);BUN and creatine clearance rate: ≥ 50 mL/min;LVEF: ≥ 50%;QTcF: < 470 ms for female and < 450 ms for male.
  9. Signed the informed consent form prior to patient entry.
  Exclusion Criteria:
  1. Patients with brain metastases who have extensive meningeal metastases and are treated with hormone dehydration.
  2. Subjects with third space fluid(such as a large amount of pleural effusion and ascites) that can not be controled by drainage or other methods. (such as pleural effusion and ascites).
  3. Received whole brain radiotherapy, chemotherapy, surgery or target therapy within 2 weeks prior to randomization. Received hormone therapy within 1 weeks prior to randomization, Received the nitrosoureas or mitomycin chemotherapy within 6 weeks prior to randomization.
  4. Participated in other clinical trial within 4 weeks prior to randomization.
  5. Treated or treating with HER2 tyrosine kinase inhibitors (TKIs) (including Lapatinib, Neratinib and Pyrotinib).
  6. Second malignancies within 5 years, except for cured carcinoma in-situ of uterine cervix, skin basal cell carcinomaand squamous-cell carcinoma.
  7. Receiving any other anti-tumor therapies at time of study screening visit.
  8. There are no other serious and/or uncontrolled diseases that may affect research participation, including any of the following: (1) unable to swallow, chronic diarrhea and intestinal obstruction and factors influencing the usage of oral administration; (2) has allergies or a known history of hypersensitivity to the drug components of this program; History of Immunodeficiency, acquired or congenital immunodeficiency (HIV positive) ,history of organ transplantation; (3) History of any kind of Heart disease, including 1) Myocardial infarction; 2) Heart failure; 3) Any other heart disease judged by researcher as not suitable for participating in this study, etc; (4) Infection.
  9. All female patients in breastfeeding period or in child-bearing period or with positive pregnancy test result or refusing to take a reliable method of birth control during the study.
  10. Any other situations judged by investigator as not suitable for participating in this study.

Relevance to patient case: not relevant