Health Condition 1: C509- Malignant neoplasm of breast of unspecified site
Conditions
Interventions
Intervention1: Pyrotinib maleate tablets, Capecitabine tablets: Pyrotinib 400 mg once daily orally + Capecitabine 1000 mg/m2 orally BID
Control Intervention1: Lapatinib ditosylate mono-hydrate tablets
Sponsors
Syngene International Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Males and females aged equal to or more than 18 years. 2. Patients with histological or cytological confirmed HER2 positive advanced breast cancer who have been previously treated with more than or equal to 1 prior HER2 directed therapy for advanced disease and for whom the investigator has planned Lapatinib plus Capecitabine as the intended regimen. Note, HER2 positive status will be assessed with 3 plus staining intensity by immune histochemistry or HER2 gene amplification by fluorescence in situ hybridisation indicating HER2 positivity. A HER2 positive breast cancer confirmed by the pathology department of the participating study centre. 3. At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1. 4. ECOG physical performance 0 to 1 5. Subjects willing to comply with protocol requirements 6. Willing to provide written informed consent 7. Lab parameters should meet the following requirements: ANC, more than or equal to 1.5 x 109 per Liter, Platelet more than or equal to 90 x 109 per Liter, Hb more than or equal to 9.0 gm per dl, Total bilirubin more than or equal to 1.0 x upper limit of normal, ALT and AST more than or equal to 2 x ULN, patients with liver metastases, less than or equal to 5 x ULN, Creatinine less than or equal to 1 x ULN, creatinine clearance less than or equal to 50 mL per min, LVEF less than or equal to 50 percent. 8. Fridericia-corrected QT interval less than 450 msec for males and less than 470 msec for females 9. Female subjects of child-bearing potential should have negative serum pregnancy test at screening and agree to use adequate birth control during the entire study period. a. For women who are not postmenopausal, postmenopausal defined as more than or equal to 12 months of Non therapy induced amenorrhea, or surgically sterile, absence of ovaries and or uterus agreement to remain abstinent or use single or combined non hormonal contraceptive methods that result in a failure rate of less than 1 percent per year during the treatment period and for at least 8 weeks after the last dose of study treatment b. Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence e.g., calendar, ovulation, or post ovulation methods and withdrawal are not acceptable methods of contraception. c. Examples of non hormonal contraceptive methods with a failure rate of less than 1 percent per year include tubal ligation, male sterilization, and certain non hormonal intrauterine devices. Alternatively, two methods, e.g., two barrier methods such as a condom and a cervical cap, may be combined to achieve a failure rate of less than 1percent per year. Barrier methods must always be supplemented with the use of a spermicide d. For men, agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of less than 1 percent per year during the treatment period and for at least 1 week after the last dose of study treatment e. Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence e.g., calendar, ovulation, or post ovulation methods and withdrawal are not acceptable methods of contraception
Exclusion criteria
Exclusion criteria: 1. History of hypersensitivity or allergy to any of the study drugs or its components 2. Received radiotherapy, chemotherapy, surgery, major surgery for breast cancer, or molecular targeted therapy within 4 weeks prior to randomization, received endocrine therapy within 7 days prior to randomization. 3. History of other malignant tumors in the past 5 years, other than cured cervical carcinoma in situ, basal or squamous cell carcinoma of skin 4. Presence of central nervous system metastases, definitive diagnosis of brain tumor by cranial CT or MRI scan 5. Presence of Dihydropyrimidine Dehydrogenase deficiency 6. Any antitumor treatment after informed consent and before randomization 7. Previous or current treatment with any tyrosine kinase inhibitor, including lapatinib, neratinib, and pyrotinib, targeting HER2 8. Previous capecitabine treatment for metastatic disease or in the neoadjuvant or adjuvant setting within 6 months before randomisation 9. History of exposure to the following cumulative doses of anthracyclines. Doxorubicin or doxorubicin liposome more than 360 mg per meter square Epirubicin more than 720 mg per meter square, Mitoxantrone more than 120 mg per meter square idarubicin more than 90 mg per meter square 10. Factors influencing the oral administration in affected patients e.g. dysphagia, chronic diarrhea, intestinal obstruction, etc. 11. Uncontrolled third space effusion, such as pleural fluid and ascites, by drainage or other clinical intervention 12. Known history of any immunodeficiency disease, acquired or congenital immunodeficiency disease, or history of organ transplantation 13. History or presence of interstitial lung disease and or pneumonitis 14. No radiologically confirmed disease progression during or after the most recent anti tumor treatment before enrollment, as assessed by the investigator 15. Subjects with significant cardiovascular history such as Congestive heart failure, myocardial infarction, angina pectoris, stroke or transient ischemic attack, arrhythmia, or any other within 6 months prior to randomisation 16. Subjects who used the concomitant drugs, enlisted in section 7.3 that interfere with liver P450 enzymes or Pgp within 5 half lives of the concomitant drugs prior to the pyrotinib administration 17. Subject having any medical condition or any significant laboratory finding, which in the opinion of the investigator, will interfere with the study results or increase the risk of adverse events. 18. Female subjects who are Pregnant or lactating 19. Subjects with history of drug or alcohol abuse 20. Receipt of any drug as part of a research study within 30 days prior to screening 21. Subjects with donation or transfusion of blood, plasma, or platelets within the past 3 months prior to randomisation 22. Known case of HIV, HBV or HCV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of Pyrotinib plus Capecita-bine compared with Lapatinib plus Capecitabine in patients with HER2-positive metastatic breast cancer.Timepoint: To evaluate the efficacy of Pyrotinib plus Capecita-bine compared with Lapatinib plus Capecitabine in patients with HER2-positive metastatic breast cancer. | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the safety and tolerability of Pyrotinib plus Capecitabine compared with Lapatinib plus Capecitabine in patients with HER2-positive meta-static breast cancer.Timepoint: 1. Objective Response Rate (defined as the proportion of patients with the best response of complete response [CR] or partial response [PR] per RE-CIST 1.1 at 12 months 2. Duration of Response, the time from the first complete or partial response to death or progression, whichever occurs first, at 12 months 3. Clinical Benefit Rate i.e., the proportion of patients with a best overall response of complete response, partial response, or stable disease for more or equal to 24 weeks, at 12 months Exploratory Endpoint: Proportion of patients with overall survival at 18 months. | — |
Countries
India
Contacts
Public ContactDr A C Gangaram
Dr Reddy s Laboratories
Outcome results
None listed