Comparing Efficacy and Safety of AryoGen Pharmed Biosimilar Trastuzumab (AryoTrust) Versus Herceptin® in Breast Cancer
- Conditions
- Malignant Neoplasm of Breast
- Interventions
- Registration Number
- NCT03425656
- Lead Sponsor
- AryoGen Pharmed Co.
- Brief Summary
This is A Phase III, randomized, two-armed, patient-outcome assessor-data analyzer blinded, parallel active controlled non-Inferiority clinical trial study to evaluate efficacy and safety of AryoTrust (Aryogen Trastuzumab in comparison to Herceptin® (Genentech/Roche) in patients with Human Epidermal Growth Factor Receptor 2-Positive breast cancer. The main objective is to verify the non-inferiority of AryoTrust (Aryogen trastuzumab) vs. Herceptin® (Genentech/Roche trastuzumab), both given concomitantly with docetaxel after doxorubicin plus cyclophosphamide in the neoadjuvant setting according to pathological complete response (pCR) as primary objective and objective response (cOR), clinical complete response (cCR), clinical partial response (cPR), clinical stable disease (cSD), clinical progressive disease (cPD), breast conservation rate as Secondary objectives of this study. Evaluating the safety and immunogenicity of AryoTrust vs. Herceptin®, are also the other secondary outcomes. This study has two arms and 108 subjects will participate with a 1:1 allocation and receive mentioned treatment randomly.
- Detailed Description
This is A Phase III, randomized, two-armed, patient-outcome assessor-data analyzer blinded, parallel active controlled non-Inferiority clinical trial study to evaluate efficacy and safety of AryoTrust (Aryogen Trastuzumab) in comparison to Herceptin® (Genentech/Roche) in patients with Human Epidermal Growth Factor Receptor 2-Positive breast cancer. Patients who met the following criteria will be recruited. The inclusion criteria are: 18-70 years old female patients, Patients with newly diagnosed stage III (locally advanced) or in-operable stage II (due to sizes larger than 5 cm or high tumor to breast ratio) tumors are candidates for participation, Willing and able to sign an informed consent, Pathological diagnosis of adenocarcinoma of the breast, ECOG status of 0-1, With any ER/PR status, HER2 positive (Immunohistochemical (IHC) 3+ intensity, amplification of the HER2 gene on fluorescence in situ hybridization (FISH+ ) or HER2 positive results of Chromogenic in situ hybridization (CISH)). Exclusion criteria are: Clinical or radiologic evidence of metastatic disease, History of any other malignancy including previous breast cancer, second non-breast malignant disease, History of previous chemotherapy, Left ventricular ejection fraction \[LVEF\] \<55% confirmed by echo cardiogram within 3 months before registration, Any prior myocardial infarction, History of documented congestive heart failure (CHF),Any prior history of arrhythmia or cardiac valvular disease requiring medications or clinically significant, Current use of medications for treatment of angina pectoris, Current uncontrolled hypertension (diastolic \> 100 mmHg or systolic \> 200 mmHg), A severe conduction abnormality (having pacemaker or diagnosed by the ECG) and any other significant cardiovascular disease, Hematologic abnormalities including baseline Absolute Neutrophil Count (ANC) of ≤1,500/µL or platelet count ≤ 100,000/µL, Liver dysfunction including (baseline) Alanine amino transferase (ALT) and/or aspartate amino transferase (AST) ≥ 3 Upper Limit Normal (ULN), Alkaline phosphatase (ALP) ≥3 ͯ ULN, serum total, bilirubin \> 1.5 ULN, Renal dysfunction, defined as serum creatinine ≥2.5 mg/dL, Pregnant, lactating women or women of childbearing potential who are not willing to use adequate contraception.
The main objective is to verify the non-inferiority of AryoTrust (Aryogen Trastuzumab) vs. Herceptin® (Genentech/Roche Trastuzumab), both given concomitantly with docetaxel after doxorubicin plus cyclophosphamide in the neoadjuvant setting according to pathological, clinical response and immunogenicity assay in patients with Human Epidermal Growth Factor Receptor 2-Positive breast cancer. The primary objective of this study is to verify the non-inferiority of AryoTrust vs. Herceptin®, given concomitantly with docetaxel after doxorubicin plus cyclophosphamide in the neoadjuvant setting according to pathological complete response (pCR) rate. The secondary objectives are to evaluate non-significance between AryoTrust and Herceptin®, given concomitantly with docetaxel after Adriamycin plus cyclophosphamide in the neoadjuvant setting according to clinical objective response (cOR), clinical complete response (cCR), clinical partial response (cPR), clinical stable disease (cSD), clinical progressive disease (cPD), breast conservation rateEvaluating the safety and immunogenicity of AryoTrust vs. Herceptin®, are also the other secondary outcomes. This study has two arms and 108 subjects will participate with a 1:1 allocation and receive AryoTrust vs. Herceptin® randomly given concomitantly with docetaxel (for four 21-day cycles) after four 14-day cycles of Doxorubicin plus cyclophosphamide For primary outcome analysis, Treatment differences in proportions will be calculated. A 95% two-sided confidence interval will be constructed and the upper bound to determine non-inferiority with a 2.5% significance level will be used.Frequency and proportions will be calculated for all secondary efficacy endpoints include clinical complete response (cCR), clinical partial response (cPR), clinical stable disease (cSD), clinical progressive disease (cPD), clinical objective response (cOR), breast conservation rate. All safety data will be analyzed descriptively by each treatment group. same protocol and procedures have been implemented by using same SOPs. Regular and strict monitoring visits have been provided to ensure all processes will be carried out in accordance with GCP. Probable variation of eligibility criteria and evaluation criteria are resolved through investigator meetings.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 108
- 18-70 years old female patients
- Patients with newly diagnosed stage III (locally advanced) or inoperable stage II (due to sizes larger than 5 cm or high tumor to breast ratio) tumors are candidates for participation.
- Willing and able to sign an informed consent
- Pathological diagnosis of adenocarcinoma of the breast
- ECOG status of 0-1
- With any ER/PR status
- HER2 positive (Immunohistochemical (IHC) 3+ intensity, amplification of the HER2 gene on fluorescence in situ hybridization (FISH+ ) or HER2 positive results of Chromogenic in situ hybridization (CISH+)).
-
Clinical or radiologic evidence of metastatic disease
-
History of any other malignancy including previous breast cancer, second non-breast malignant disease
-
History of previous chemotherapy
-
Left ventricular ejection fraction [LVEF] <55% confirmed by echo cardiogram within 3 months before registration, Any prior myocardial infarction, History of documented congestive heart failure (CHF),Any prior history of arrhythmia or cardiac valvular disease requiring medications or clinically significant, Current use of medications for treatment of angina pectoris, Current uncontrolled hypertension (diastolic > 100 mmHg or systolic > 200 mmHg), A severe conduction abnormality (having pacemaker or diagnosed by the ECG) and any other significant cardiovascular disease.
-
Hematologic abnormalities including baseline Absolute Neutrophil Count (ANC) of ≤1,500/µL or platelet count ≤ 100,000/µL
-
Liver dysfunction including : (baseline)
- Alanine amino transferase (ALT) and/or aspartate amino transferase (AST) ≥ 3 Upper Limit Normal (ULN)
- Alkaline phosphatase (ALP) ≥3 ͯ ULN
- serum total bilirubin > 1.5 ULN
-
Renal dysfunction, defined as serum creatinine ≥2.5 mg/dL
-
Pregnant, lactating women or women of childbearing potential who are not willing to use adequate contraception
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Trastuzumab (AryoTrust) Trastuzumab plus docetaxel (for four 21-day cycles) after four 14-day cycles of Doxorubicin plus cyclophosphamide Trastuzumab (AryoTrust) is given concomitantly with docetaxel (for four 21-day cycles) after four 14-day cycles of Doxorubicin plus cyclophosphamide Trastuzumab (Herceptin) Trastuzumab plus docetaxel (for four 21-day cycles) after four 14-day cycles of Doxorubicin plus cyclophosphamide Trastuzumab (Herceptin) is given concomitantly with docetaxel (for four 21-day cycles) after four 14-day cycles of Doxorubicin plus cyclophosphamide
- Primary Outcome Measures
Name Time Method Pathologic Complete Response week 23 the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes
- Secondary Outcome Measures
Name Time Method Clinical Objective Response week 21 clinical Complete Response + clinical Partial Response
Breast Conservation Rate week 23 Patients who underwent lumpectomy
Safety Assessment by Evaluation of Adverse Events (AEs) and Abnormal Laboratory Results up to week 26 Safety assessment, including the incidence of all reported AEs and abnormal laboratory results was done. All AEs were classified based on the Medical Dictionary for Regulatory Activities (MedDRA Desktop Browser 4.0 Beta) terms as System Organ Class (SOC) and Preferred Term (PT). All the reported events were graded according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Moreover, seriousness of AEs was assessed according to International Council for Harmonization (ICH-E2B) guidelines. The causality relation was assessed based on the World Health Organization (WHO) criteria.
The Number of Participants With Anti-drug Antibodies Against Trastuzumab (AryoTrust) week 10, week 13, week 19, week 26 The levels of anti-drug antibodies against Trastuzumab ( aryotrust ) are assessed via ELISA and the percantage of positive value are reported
Trial Locations
- Locations (19)
Javadol Aemeh Clinic
🇮🇷Kerman, Iran, Islamic Republic of
Tohid Hospital
🇮🇷Sanandaj, Iran, Islamic Republic of
Masood Clinic
🇮🇷Tehran, Iran, Islamic Republic of
Toos Hospital
🇮🇷Tehran, Iran, Islamic Republic of
Mortazavizadeh Clinic
🇮🇷Yazd, Iran, Islamic Republic of
Shafa Hospital
🇮🇷Ahvaz, Iran, Islamic Republic of
Sheikh Mofid Clinic
🇮🇷Isfahan, Iran, Islamic Republic of
Park clinic
🇮🇷Kerman, Iran, Islamic Republic of
Shahid Faqihi Hospital
🇮🇷Shiraz, Iran, Islamic Republic of
Aliebne Abitaleb Hospital
🇮🇷Zahedan, Iran, Islamic Republic of
Jahad Daneshgahi Clinic
🇮🇷Tehran, Iran, Islamic Republic of
Rasool Akram Hospital
🇮🇷Tehran, Iran, Islamic Republic of
Imam Reza Hospital
🇮🇷Mashhad, Iran, Islamic Republic of
Payandeh Clinic
🇮🇷Kermanshah, Iran, Islamic Republic of
Booali Hospital
🇮🇷Tehran, Iran, Islamic Republic of
Mehrad Hospital
🇮🇷Tehran, Iran, Islamic Republic of
Baqiatallah Hospital
🇮🇷Tehran, Iran, Islamic Republic of
Firoozgar Hospital
🇮🇷Tehran, Iran, Islamic Republic of
Imam Khomeini hospital
🇮🇷Tehran, Iran, Islamic Republic of