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IRCT201606226135N7 IRCT 2016-06-25 Aryogen pharmed Company Efficacy and safety in AryoTrust™ (Aryogen trastuzumab) vs Herceptin® (Genentech/Roche trastuzumab), a non inferiority trial A Phase III, randomized, two-armed, patient-outcome assessor-data analyzer blinded, parallel active controlled non-Inferiority clinical trial study of AryoTrust™ (AryogenTrastuzumab) efficacy and safety in Human Epidermal Growth Factor Receptor 2–Positive breast cancer in comparison to Herceptin® (Genentech/Roche) control. 2016-07-02 anticipated 108 Complete https://irct.ir/trial/6573 interventional Randomization: Randomized, Blinding: Triple blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Randomization description: The randomization is based on blocked randomization. Patient's allocation will be carried on 1:1 allocation ratio by 27 blocks (length of each block is 4). Randomization sequence will be generated using the random generation command in Microsoft Excel (RANDBETWEEN), Blinding description: Both trastuzumab products are indistinguishable for patients and health care providers. So it will be possible to make patients blind about the treatment group which they have been allocated to. In addition to this, the outcome evaluators and data managers (data analyzer) will not be aware of patients’ allocations. 3 breast cancer patients with HER2-positive. Intervention 1: Intervention group: All patients are scheduled to receive Doxorubicin + Cyclophosphamide/Docetaxel+AryoTrust regimen as detailed bellow: Doxorubicin + Cyclophosphamide phase: (Cycle length: 14 days.Total cycles: 4) CyclesDoxorubicin, 60 mg/m2 IV + Cyclophosphamide,600 mg/m2 IV. Docetaxel + AryoTrust™ phase: (Cycle length: 21 days.Total cycles: 4 cycles) Docetaxel, 100 mg/m2 IV, AryoTrust™(Produced by AryoGEN Pharmed) 8 mg/kg IV loading dose (at cycle 1), followed by 6 mg/kg at subsequent cycles. Intervention 2: Control Group: All patients are scheduled to receive Doxorubicin + Cyclophosphamide/Docetaxel+Herceptin regimen as detailed bellow: Doxorubicin + Cyclophosphamide phase: (Cycle length: 14 days.Total cycles: 4) CyclesDoxorubicin, 60 mg/m2 IV + Cyclophosphamide,600 mg/m2 IV. Docetaxel + Herceptin phase: (Cycle length: 21 days.Total cycles: 4 cycles) Docetaxel, 100 mg/m2 IV, Herceptin (Produced by Roche) 8 mg/kg IV loading dose (at cycle 1), followed by 6 mg/kg at subsequent cycles. Undecided - It is not yet known if there will be a plan to make this available Justification or reason for indecision in sharing IPD is The sponsor has not decided to share IPD
public Somayeh Amini
Shahrak gharb- Farahzadi Blvd., West Dadman Blvd.,derakhti St,-Khorasan- dead end i, No. 2
Tehran Iran (Islamic Republic of) 88821 +98 21 8808 8821 Amini.s@orchidpharmed.com Orchid pharmed Company scientific Reza Safaie Nodehi
Keshavarz Blvd., Imam Khomeini Hospital Complex
Tehran Iran (Islamic Republic of) 350649 +98 21669350649 safano1334@gmail.com Tehran University of Medical Sciences Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) 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 18 years 70 years Female 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 vascular 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 NeutrophilCount (ANC) of≤1,500/µL or platelet count ≤ 100,000/µL Liver dysfunction including : 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 creatinin ≥2.5 mg/dL Pregnant, lactating women or women of childbearing potential who are not willing to use adequate contraception C50 Malignant neoplasm of breast Treatment - Drugs Treatment - Drugs Intervention group: All patients are scheduled to receive Doxorubicin + Cyclophosphamide/Docetaxel+AryoTrust regimen as detailed bellow: Doxorubicin + Cyclophosphamide phase: (Cycle length: 14 days.Total cycles: 4) CyclesDoxorubicin, 60 mg/m2 IV + Cyclophosphamide,600 mg/m2 IV. Docetaxel + AryoTrust™ phase: (Cycle length: 21 days.Total cycles: 4 cycles) Docetaxel, 100 mg/m2 IV, AryoTrust™(Produced by AryoGEN Pharmed) 8 mg/kg IV loading dose (at cycle 1), followed by 6 mg/kg at subsequent cycles Control Group: All patients are scheduled to receive Doxorubicin + Cyclophosphamide/Docetaxel+Herceptin regimen as detailed bellow: Doxorubicin + Cyclophosphamide phase: (Cycle length: 14 days.Total cycles: 4) CyclesDoxorubicin, 60 mg/m2 IV + Cyclophosphamide,600 mg/m2 IV. Docetaxel + Herceptin phase: (Cycle length: 21 days.Total cycles: 4 cycles) Docetaxel, 100 mg/m2 IV, Herceptin (Produced by Roche) 8 mg/kg IV loading dose (at cycle 1), followed by 6 mg/kg at subsequent cycles Pathologic Complete Response (pCR). Timepoint: following completion of neoadjuvant systemic therapy. Method of measurement: the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes. Clinical Complete Response (cCR). Timepoint: after completion of neoadjuvant systemic therapy. Method of measurement: Disappearance of lesions in imaging. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Clinical Partial Response (cPR). Timepoint: after completion of neoadjuvant systemic therapy. Method of measurement: At least a 30% decrease in the sum of diameters of target lesions through imaging. Clinically Stable Disease (cSD). Timepoint: after completion of neoadjuvant systemic therapy. Method of measurement: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD through imaging. Clinical Progressive Disease (cPD). Timepoint: after completion of neoadjuvant systemic therapy. Method of measurement: at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm through imaging. Clinical Objective Response(cOR). Timepoint: after completion of neoadjuvant systemic therapy. Method of measurement: cOR= cCR+ cPR. Breast conservation rate. Timepoint: After surgery. Method of measurement: number of mastectomy or Breast conservative surgery. Immunogenicity. Timepoint: Week 10, 13, 19 and 26. Method of measurement: Laboratory results. Adverse events. Timepoint: Every cycle. Method of measurement: Laboratory data and patient assessments. NCT03425656 clinicaltrial.gov Aryogen pharmed Company Approved 2016-06-22 Tehran university of medical science, Medical Ethics Committee Tehran university of medical science Tehran Tehran Iran (Islamic Republic of) Approved 2016-07-17 Isfehan university of medical science دانشگاه علوم پزشکی اصفهان isfehan Isfehan Iran (Islamic Republic of)