Comparing Efficacy and Safety of AryoGen Pharmed Biosimilar Trastuzumab (AryoTrust) Versus Herceptin® in Breast Cancer
Condition: Malignant Neoplasm of Breast
MeSH terms: Breast Neoplasms; Neoplasms
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Trastuzumab plus docetaxel (for four 21-day cycles) after four 14-day cycles of Doxorubicin plus cyclophosphamide
Intervention type(s): Drug
Intervention description(s): Trastuzumab (8 mg/kg IV loading dose at cycle 1, followed by 6 mg/kg at subsequent cycles) is given concomitantly with docetaxel (100 mg/m2 IV) for four 21-day cycles after four 14-day cycles of Doxorubicin (60 mg/m2 IV) plus cyclophosphamide (600 mg/m2 IV)
Intervention MeSH terms: Cyclophosphamide; Docetaxel; Doxorubicin; Trastuzumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: breast cancer; AryoTrust; Herceptin®; non-Inferiority