Women aged 18 to 75 years with HER2-positive metastatic breast cancer Biosimilar, efficacy, safety, trastuzumab, Real-world, metastatic breast cancer, HER2-positive
Conditions
Interventions
Participants will receive WT-1 Trastuzumab plus paclitaxel for 6 to 8 cycles, followed by WT-1 Trastuzumab monotherapy every three weeks until disease progression
Experimental Biological/Vaccine
WT-1 Trastuzumab (HERDARA 150 mg)
Sponsors
Chulabhorn Foundation by Chulabhorn Research Institute
Eligibility
Sex/Gender
Female
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Female patients aged 18 to 75 years 2. Histologically confirmed breast cancer with metastatic disease 3. At least one measurable lesion according to RECIST 1.1 criteria (Note: bone, lesions, ascites and pleural effusions are not considered measurable). The minimum indicator lesion size is defined as follows: - at least 10 mm measured by spiral CT - at least 20 mm measured by other techniques - Lymph node lesion short axis diameter of at least 15 mm by spiral CT 4. Overexpression of HER2 (3+) as determined by immunohistochemistry (IHC) or amplification of HER2/c-erB2 as determined by Fluorescence in Situ Hydridisation (FISH) or Dual-colour silver-enhanced In Situ Hydridisation (DISH) of primary tumor or metastasis. 5. ECOG performance status 0 to 1. 6. Baseline LVEF at least 50 percent (measured by echocardiography or MUGA). 7. Patients should have recovered from the acute reversible effects of prior chemotherapy (only allowed if given as adjuvant setting) and radiotherapy. The general period considering for recovery is 4 weeks. 8. Patients receiving hormone therapy for breast cancer should stop for 4 weeks prior to the first dose of study medication. 9. Patients who received chemotherapy for adjuvant therapy may be enrolled if the disease recurrences more than 12 months after the last dose of chemotherapy. 10. Patients who received Doxorubicin plus Cyclophosphamide (AC) should stop prior to the first dose of study medication for at least 3 weeks. 11. Signed written informed consent obtained prior to any study specific screening procedures. 12. Able to comply with study protocol.
Exclusion criteria
Exclusion criteria: An individual who meets any of the following criteria will be excluded from participation in this study: 1. Pregnant or lactating women. Documentation of negative pregnancy test must be available for pre-menopausal women with intact reproductive organs and for women less than one year after menopause. 2. Women of childbearing potential unless - Surgically sterile or - Using adequate measures of contraception (intra-uterine device or barrier method of contraception in conjunction with spermicidal jelly). 3. Patients who have previously been treated with any chemotherapy for metastatic disease. Prior use of chemotherapy for adjuvant will be allowed. 4. History of documented congestive heart failure, angina pectoris requiring antianginal medication, evidence of transmural infarction on ECG, poorly controlled hypertension (systolic greater than 180 mmHg or diastolic greater than 100 mmHg), clinically significant valvular heart diseases or high risk of uncontrolled arrhythmias. 5. Patients with history of uncontrolled seizure, central nervous system disorders or psychiatric disability, which could affect ability to give informed consent or compliance with study procedures. 6. Patients with evidence of CNS metastasis. 7. Patients with dyspnoea at rest due to malignant or other disease, or who require supportive oxygen therapy. Patients with pre-existing lung disease or advanced pulmonary involvement may be at increased risk of serious toxicities and should be evaluated carefully before entry into the study. 8. Treatment with any investigational drug within 30 days before beginning of treatment with study drug. 9. Patients with the following baseline laboratory values: - Absolute neutrophil count less than 1.5 times 10 to the power of 9 cells per litre. Platelet count less than 100 times 10 to the power of 9 cells per litre. - serum bilirubin greater than 1.5 times ULN (except when Gilbert's syndrome is clearly documented and other LFTs are normal) - AST/ALT greater than 1.5 times ULN associated with alkaline phosphatase greater than 2.5 times ULN - Isolated ALT and/or AST greater than 1.5 times ULN. At the investigator's discretion, patients with isolated ALT or AST greater than 1.5 times ULN and less than or equal to 2.5 times ULN may be enrolled. Patients with documented liver metastasis can be enrolled if baseline AST/ALT less than 5 times ULN. Such patients must be monitored carefully. After a cohort such patients have been enrolled and monitored, it may be possible to enroll patients with higher isolated elevations of ALT and/or AST. - Isolated alkaline phosphatase greater than 5 times ULN (except when bone metastases are present in absence of any liver disorders). 10. Patients with serious uncontrolled intercurrent illness including infections (bacterial or viral) and poorly controlled diabetes mellitus. 11. History of prior malignancy which could affect compliance with the protocol or interpretation of results. Patients with a history of curatively treated non-melanomatous skin carcinoma or In Situ carcinoma of the cervix and patients with other malignancies which have been treated with curative intent and remained disease free for more than 5 years are eligible. 12. Patients receiving chronic systemic corticosteroid therapy. However, inhaled steroids and short course of oral steroids for pre-medication or anti-emesis are allowed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Efficacy: Objective response At Cycle 4, and end of combination of WT-1 Trastuzumab (HERDARA) and chemotherapy Response rate ,2.Progression-Free Survival From baseline until disease progression or death from any cause, whichever occurs first Progression-Free Survival rate,3.Safety: Adverse events After receive infusion of WT-1 Trastuzumab (HERDARA) combination with chemotherapy throughout the period of receiving WT-1 Trastuzumab (HERDARA) Adverse events according to NCI CTCAE grading version 6.0 ,4.Immunogenicity At baseline prior to first infusion of WT-1 Trastuzumab (HERDARA), end of combination of WT-1 Trastuzumab (HERDARA) and chemotherapy and at one year after receiving WT-1 Trastuzumab. (HERDARA) Anti-drug Antibody | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Time to Progression: TTP Time point after first infusion to first time of disease progression confirmed by radio-imaging Time to Progression period ,2. One-Year Survival Rate One year after receiving WT-1 Trastuzumab (HERDARA) Mortality Rate,3. Overall Survival Rate After receiving first dose of WT-1 Trastuzumab (HERDARA) through completion of 1 year of treatment, with subsequent follow-up under the compassionate use program Mortality Rate | — |
Countries
Thailand
Contacts
Public ContactCharlermchai Artpradit
Chulabhorn Research Institute
Outcome results
None listed