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IRCT20211218053442N2 IRCT 2025-01-04 Zistdaru Danesh Co. Evaluation the efficacy and safety of Cetuximab manufactured by Zistdaru danesh Co. compared to Erbitux in the patients with head and neck squamous cell carcinoma. Evaluation of the efficacy and safety of Abycet (Cetuximab, manufactured by ZistDaru Danesh) compared to Erbitux (Merck®) in patients with head and neck squamous cell carcinoma undergoing treatment with the TPEx regimen (Docetaxel, Platinum, and Cetuximab) 2025-01-20 anticipated 216 Complete https://irct.ir/trial/73435 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Randomization description: Randomization in this study will stratified block. Stratification is done based on these factors: 1. Type of disease: locoregional recurrence alone or metastatic evolution with or without locoregional recurrence or Induction chemotherapy in locoregionally advanced HNSCC 2. Treatment with Carboplatin or Cisplatin A block random sequence is formed in each layer. Randomization sheet will be built with blocks of 2 and 4 for a total of 216 patients by www.sealedenvelope.com platform. When randomization is done, each patient receive a code. The code will consist of three digits (corresponding to the randomization number) and four letters (corresponding to the first two letters of the name and the first two letters of the last name). Randomization numbers are determined sequentially. The randomization list is prepared by the CRO and maintained by a member of the executive team outside the study, Blinding description: This study is a double-blind study. All treatment personnel and those involved in the study and patients are unaware of who is receiving which of the two drugs. Both study drugs have completely the same vial size and packaging. The team that evaluates the outcomes of study will be completely different from those involved in the treatment of the patients. The randomization schedule will be confidential and with limited access at the randomization study implementation center, a copy will be kept at the CRO. Except for the cases specified in the protocol and only in those cases where the safety of the patient is dependent on the knowledge of the individual's study group, the assignment of people to the groups will not be announced until the analysis is done. 3 Head and Neck Squamous Cell Carcinoma (HNSCC). Intervention 1: Intervention group: Cetuximab bio-similar of Zistdaru Danesh Co. ® (100 mg/20 ml vial) which is administered intravenously in the first, fourth, seventh and tenth weeks together with Docetaxel (75mg/m2) and Cisplatin (75mg/m2) or Carboplatin and in the other weeks alone with an initial dose of 400mg/m2 over 120 minutes and a weekly dose of 250mg/m2 over 60 minutes via an infusion pump for up to 12 weeks (Locally advanced patients will receive Cetuximab in the announced order but for 7 weeks, i.e. one week after the third cycle of chemotherapy). It should be noted that one hour after the end of the Cetuximab infusion, Docetaxel and then Cisplatin/Carboplatin are infused. Diphenhydramine or another H1 antagonist such as Chlorpheniramine is administered before starting Cetuximab administration. It is also necessary to receive 8 mg of Dexamethasone one hour before the Cetuximab injection. In cycles in which Cetuximab is injected with Docetaxel and Cisplatin/Carboplatin, a premedication is performed to prevent nausea and vomiting, which includes a 4-drug treatment (Aprepitant (125 mg on day 1 and 80 mg on days 2 and 3), Granisetron (3 mg on days 1, 8 and 15), Dexamethasone (12 mg on day 1 and 8 mg on days 2, 3 and 4) and Olanzapine (5 mg for 4 days)). GCSF is also injected every 24 hours for up to three days in each chemotherapy cycle as a prophylaxis. Intervention 2: Control group: Erbitux of Merck® (100 mg/20 ml vial) which is administered intravenously in the first, fourth, seventh and tenth weeks together with Docetaxel (75mg/m2) and Cisplatin (75mg/m2) or Carboplatin and in the other weeks alone with an initial dose of 400mg/m2 over 120 minutes and a weekly dose of 250mg/m2 over 60 minutes via an infusion pump for up to 12 weeks (Locally advanced patients will receive Cetuximab in the announced order but for 7 weeks, i.e. one week after the third cycle of chemotherapy). It should be noted that one hour after the end of the Cetuximab infusion, Docetaxel and then Cisplatin/Carboplatin are infused. Diphenhydramine or another H1 antagonist such as chlorpheniramine is administered before starting Cetuximab administration. It is also necessary to receive 8 mg of Dexamethasone one hour before the Cetuximab injection. In cycles in which Cetuximab is injected with Docetaxel and Cisplatin/Carboplatin, a premedication is performed to prevent nausea and vomiting, which includes a 4-drug treatment (Aprepitant (125 mg on day 1 and 80 mg on days 2 and 3), Granisetron (3 mg on days 1, 8 and 15), Dexamethasone (12 mg on day 1 and 8 mg on days 2, 3 and 4) and Olanzapine (5 mg for 4 days)). GCSF is also injected every 24 hours for up to three days in each chemotherapy cycle as a prophylaxis. 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 No more information.
public Zahra Rezagholi
Unit 404, 4th Floor, Rosemal Building, Hemmet Expressway, Tehran, Iran
Tehran Iran (Islamic Republic of) 1498711712 +98 21 4824 1000 rezagholi.z@zistdaru.com Zistdaru Danesh Co. scientific Dr Farhad Samie
Number 260, west Fatemi street, Tehran
Tehran Iran (Islamic Republic of) ۱۴۱۹۷۳۳۱۴۱ +98 21 6643 5149 samieifarhad@yahoo.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) Patients older than 18 years and less than 85 years Confirmed pathology of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, paranasal sinus cancer or larynx Locally advanced or metastatic or recurrent disease that are not candidates for local treatment At least one measurable lesion by CT or MRI (1.1 RECIST) Performance Status less than 2 according to ECOG Serum creatinine less than 1.5 mg/dL Hematological tests are as follows: Neutrophils more than 1500 cells per microliter, Platelets more than 100000 per microliter, Hemoglobin more than 9 g/dL The function of the liver is as follows: Direct bilirubin level less than 1.5 mg/dL, AST and ALT level less than 3 times ULN, Liver alkaline phosphatase less than 3 times ULN Albumin level greater than or equal to 3 g/dL Negative pregnancy blood test in women of childbearing age 28 days before starting the drug Consent to use a contraceptive method (both men and women (of reproductive age) who are sexually active must use contraceptive methods during treatment and for at least 6 months after treatment.) Sign the informed consent form 18 years 85 years Both Patients with nasopharyngeal cancer or unknown origin Patients with HPV positive oropharynx (according to the pathology report) In locally advanced patients: previous systemic chemotherapy for the treatment of HNSCC and in metastatic or recurrent patients: previous systemic chemotherapy except in cases prescribed for the treatment of locally advanced disease and more than 3 months have passed since the last dose. Surgery or radiotherapy within 6 weeks before study entry Received prior anti-EGFR therapy less than 6 months prior to study entry History of hypersensitivity to cisplatin, carboplatin, docetaxel or cetuximab Brain or leptomeningeal metastasis NYHA IV-III heart failure, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the past 12 months Other malignancies within 1 years prior to randomization, excluding treated basal skin cancer and cervical carcinoma Active infections (requiring intravenous antibiotics), active TB infection, HIV, and hepatitis C and B A significant disease that, according to the researcher, does not make the patient a candidate for the study Pregnant or lactating women Treatment - Drugs Treatment - Drugs Intervention group: Cetuximab bio-similar of Zistdaru Danesh Co. ® (100 mg/20 ml vial) which is administered intravenously in the first, fourth, seventh and tenth weeks together with Docetaxel (75mg/m2) and Cisplatin (75mg/m2) or Carboplatin and in the other weeks alone with an initial dose of 400mg/m2 over 120 minutes and a weekly dose of 250mg/m2 over 60 minutes via an infusion pump for up to 12 weeks (Locally advanced patients will receive Cetuximab in the announced order but for 7 weeks, i.e. one week after the third cycle of chemotherapy). It should be noted that one hour after the end of the Cetuximab infusion, Docetaxel and then Cisplatin/Carboplatin are infused. Diphenhydramine or another H1 antagonist such as Chlorpheniramine is administered before starting Cetuximab administration. It is also necessary to receive 8 mg of Dexamethasone one hour before the Cetuximab injection. In cycles in which Cetuximab is injected with Docetaxel and Cisplatin/Carboplatin, a premedication is performed to prevent nausea and vomiting, which includes a 4-drug treatment (Aprepitant (125 mg on day 1 and 80 mg on days 2 and 3), Granisetron (3 mg on days 1, 8 and 15), Dexamethasone (12 mg on day 1 and 8 mg on days 2, 3 and 4) and Olanzapine (5 mg for 4 days)). GCSF is also injected every 24 hours for up to three days in each chemotherapy cycle as a prophylaxis. Control group: Erbitux of Merck® (100 mg/20 ml vial) which is administered intravenously in the first, fourth, seventh and tenth weeks together with Docetaxel (75mg/m2) and Cisplatin (75mg/m2) or Carboplatin and in the other weeks alone with an initial dose of 400mg/m2 over 120 minutes and a weekly dose of 250mg/m2 over 60 minutes via an infusion pump for up to 12 weeks (Locally advanced patients will receive Cetuximab in the announced order but for 7 weeks, i.e. one week after the third cycle of chemotherapy). It should be noted that one hour after the end of the Cetuximab infusion, Docetaxel and then Cisplatin/Carboplatin are infused. Diphenhydramine or another H1 antagonist such as chlorpheniramine is administered before starting Cetuximab administration. It is also necessary to receive 8 mg of Dexamethasone one hour before the Cetuximab injection. In cycles in which Cetuximab is injected with Docetaxel and Cisplatin/Carboplatin, a premedication is performed to prevent nausea and vomiting, which includes a 4-drug treatment (Aprepitant (125 mg on day 1 and 80 mg on days 2 and 3), Granisetron (3 mg on days 1, 8 and 15), Dexamethasone (12 mg on day 1 and 8 mg on days 2, 3 and 4) and Olanzapine (5 mg for 4 days)). GCSF is also injected every 24 hours for up to three days in each chemotherapy cycle as a prophylaxis. Disease Control Rate (complete response (CR) or partial response (PR) or stable disease (SD) according to RECIST 1.1 criteria) at the end of chemotherapy. Timepoint: Week 12 in metastatic and recurrent patients, week 8 in locally advanced patients. Method of measurement: Imaging. Comparison of Objective Response Rate (complete response (CR) or partial response (PR) based on RECIST 1.1 criteria) at the end of chemotherapy cycles in Abycet group compared to Erbitux. Timepoint: At the end of chemotherapy cycles. Method of measurement: Imaging. Overall response rate (complete response (CR) or partial response (PR) assessed at the end of the second cycle of chemotherapy (6th week)). Timepoint: At the end of the second cycle of chemotherapy (sixth week). Method of measurement: Imaging. Percentage of candidate patients receiving cetuximab maintenance dose (complete response (CR), partial response (PR) or stable disease (SD)). Timepoint: At the end of chemotherapy cycles. Method of measurement: Imaging. Patient compliance to chemotherapy combined with cetuximab. Timepoint: At the end of chemotherapy cycles. Method of measurement: Checking the sequence and number of cetuximab doses and chemotherapy administered (insufficient compliance for cetuximab is defined as the patient missing more than 2 consecutive infusions of cetuximab, even if the missed infusions were due to adverse events. insufficient compliance for chemotherapy is defined as the patient missing more than 2 consecutive infusions of chemotherapy, even if the missed infusions were due to adverse events.). Health-related quality of life. Timepoint: In the screening visit and the final week of the study (week 8 for locally advanced patients and week 12 for metastatic and recurrent patients). Method of measurement: Questionnaire (EORTC QLQ-C30, QLQ-H&N). Safety outcome. Timepoint: For 12 weeks based on the reports and reviews done in weekly visits. Method of measurement: Safety will be evaluated based on side effect reports, laboratory test results, and vital signs measurements. Adverse events will be evaluated according to the National Cancer Institute CTC AE guidelines (v.5.0), which are grade 1 mild, moderate grade 2, severe grade 3, and life-threatening grade 4. The result of immunogenicity for the measurement of anti-drug antibodies (ADA) and neutralizing antibodies (NAB) on a subset of patients (40 patients in each arm). Timepoint: Before the injection of the first week and the last week of cetuximab injection (week 12). Method of measurement: Laboratory test. Zistdaru Danesh Co. Approved 2018-10-28 Tehran University of Medical Sciences Vice-Chancellor in Research Affairs-Tehran University of Medical Science, 6th floor, near Qods st, keshavarz blvd. Tehran Tehran Iran (Islamic Republic of)