Protocol summary
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Study aim
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Evaluation of the efficacy and safety of Abycet compared to Erbitux in patients with HNSCC under treatment with the TPEx regimen
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Design
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A phase 3, multicenter, randomized, two-arm, double-blinded, parallel, active-controlled clinical trial on 216 patients. randomization is stratified block
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Settings and conduct
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This double-blinded (patient and outcome assessor), multicenter study will be conducted in Tehran, Shiraz, Mashhad, Yazd, Kermanshah, Ahwaz, and Tabriz on patients with HNSCC treated with the TPEx regimen.
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Participants/Inclusion and exclusion criteria
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Inclusion Criteria:
Age 18-85 years; Confirmed pathology of SCC of the oral cavity, oropharynx, hypopharynx, larynx or paranasal sinus cancer; Locally advanced or metastatic or recurrent disease; At least one measurable lesion by CT or MRI; ECOG < 2; SrCr ≤ 1.5 mg/dL; Normal Neutrophils, Platelets ˃ 100,000/mcl, Hemoglobin> 9 g/dL; Adequate liver function; Albumin level ≥ 3 g/dL; Negative pregnancy test; Consent to use a contraceptive method; Sign the ICF
Exclusion Criteria:
Patients with nasopharyngeal cancer or unknown origin; HPV + oropharynx; Previous chemotherapy except in metastatic or recurrent cases prescribed for the treatment of locally advanced disease and more than 3 months have passed; Surgery or radiotherapy within 6 weeks; Received prior anti-EGFR therapy less than 6 months; History of hypersensitivity to cisplatin, carboplatin, docetaxel or cetuximab; Brain or leptomeningeal metastasis; Patients with severe cardiovascular diseases or history of MI in the past year; Other malignancies within 1 years, excluding treated basal skin cancer and cervical carcinoma; Active severe infections, active TB, HIV, and hepatitis C and B
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Intervention groups
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Abycet (cetuximab, manufactured by ZistDaru Danesh) compared to Erbitux® (Merck) in TPEx regimen
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Main outcome variables
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Disease Control Rate at the end of chemotherapy
General information
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Reason for update
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Following approval from the Iran Food and Drug Administration regarding changes to three eligibility criteria, three approved changes were revised.
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20211218053442N2
Registration date:
2025-01-04, 1403/10/15
Registration timing:
prospective
Last update:
2025-05-25, 1404/03/04
Update count:
2
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Registration date
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2025-01-04, 1403/10/15
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2025-01-20, 1403/11/01
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Expected recruitment end date
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2026-03-06, 1404/12/15
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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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)
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Public title
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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.
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
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
Exclusion criteria:
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
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Age
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From 18 years old to 85 years old
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Gender
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Both
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Phase
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3
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Groups that have been masked
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- Participant
- Investigator
- Outcome assessor
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Sample size
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Target sample size:
216
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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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.
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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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.
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Placebo
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Not used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2018-10-28, 1397/08/06
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Ethics committee reference number
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IR.TUMS.VCR.REC.1397.553
Health conditions studied
1
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Description of health condition studied
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Head and Neck Squamous Cell Carcinoma (HNSCC)
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ICD-10 code
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ICD-10 code description
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Primary outcomes
1
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Description
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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
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Timepoint
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Week 12 in metastatic and recurrent patients, week 8 in locally advanced patients
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Method of measurement
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Imaging
Secondary outcomes
1
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Description
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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
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Timepoint
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At the end of chemotherapy cycles
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Method of measurement
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Imaging
2
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Description
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Overall response rate (complete response (CR) or partial response (PR) assessed at the end of the second cycle of chemotherapy (6th week))
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Timepoint
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At the end of the second cycle of chemotherapy (sixth week)
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Method of measurement
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Imaging
3
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Description
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Percentage of candidate patients receiving cetuximab maintenance dose (complete response (CR), partial response (PR) or stable disease (SD))
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Timepoint
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At the end of chemotherapy cycles
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Method of measurement
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Imaging
4
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Description
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Patient compliance to chemotherapy combined with cetuximab
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Timepoint
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At the end of chemotherapy cycles
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Method of measurement
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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.)
5
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Description
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Health-related quality of life
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Timepoint
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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)
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Method of measurement
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Questionnaire (EORTC QLQ-C30, QLQ-H&N)
6
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Description
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Safety outcome
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Timepoint
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For 12 weeks based on the reports and reviews done in weekly visits
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Method of measurement
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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.
7
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Description
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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)
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Timepoint
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Before the injection of the first week and the last week of cetuximab injection (week 12)
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Method of measurement
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Laboratory test
Intervention groups
1
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Description
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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.
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Category
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Treatment - Drugs
2
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Description
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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.
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Zistdaru Danesh Co.
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Proportion provided by this source
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100
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Public or private sector
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Private
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Industry
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Undecided - It is not yet known if there will be a plan to make this available
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Study Protocol
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Undecided - It is not yet known if there will be a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be a plan to make this available
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Clinical Study Report
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Undecided - It is not yet known if there will be a plan to make this available
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Analytic Code
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Undecided - It is not yet known if there will be a plan to make this available
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Data Dictionary
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Undecided - It is not yet known if there will be a plan to make this available