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)
Evaluation of the efficacy and safety of Abycet compared to Erbitux in patients with HNSCC under treatment with the TPEx regimen
Design
A phase 3, multicenter, randomized, two-arm, double-blinded, parallel, active-controlled clinical trial on 216 patients. randomization is stratified block
Settings and conduct
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.
Participants/Inclusion and exclusion criteria
Inclusion Criteria:
Age 18-71 years; Confirmed pathology of SCC of the oral cavity, oropharynx, hypopharynx, or larynx; 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, paranasal sinus 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
Intervention groups
Abycet (cetuximab, manufactured by ZistDaru Danesh) compared to Erbitux® (Merck) in TPEx regimen
Main outcome variables
Disease Control Rate at the end of chemotherapy
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20211218053442N2
Registration date:2025-01-04, 1403/10/15
Registration timing:prospective
Last update:2025-01-04, 1403/10/15
Update count:2
Registration date
2025-01-04, 1403/10/15
Registrant information
Name
Hooshmand Ilka
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 4231 8000
Email address
jahan.a@zistdaru.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2025-01-20, 1403/11/01
Expected recruitment end date
2026-03-06, 1404/12/15
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
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)
Public title
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.
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Patients older than 18 years and less than 71 years
Confirmed pathology of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, 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 14 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, paranasal sinus 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
Age
From 18 years old to 71 years old
Gender
Both
Phase
3
Groups that have been masked
Participant
Investigator
Outcome assessor
Sample size
Target sample size:
216
Randomization (investigator's opinion)
Randomized
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 (investigator's opinion)
Double blinded
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.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Tehran University of Medical Sciences
Street address
Vice-Chancellor in Research Affairs-Tehran University of Medical Science, 6th floor, near Qods st, keshavarz blvd.
City
Tehran
Province
Tehran
Postal code
1417613151
Approval date
2018-10-28, 1397/08/06
Ethics committee reference number
IR.TUMS.VCR.REC.1397.553
Health conditions studied
1
Description of health condition studied
Head and Neck Squamous Cell Carcinoma (HNSCC)
ICD-10 code
ICD-10 code description
Primary outcomes
1
Description
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
Secondary outcomes
1
Description
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
2
Description
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
3
Description
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
4
Description
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.)
5
Description
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)
6
Description
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.
7
Description
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
Intervention groups
1
Description
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.
Category
Treatment - Drugs
2
Description
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.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Cancer Institute (Imam Khomeini Hospital)
Full name of responsible person
Reza Ghalehtaki
Street address
Tehran, end of Keshavarz Boulevard, Dr. Gharib Street, eastern side of the Imam Khomeini Hospital Complex
City
Tehran
Province
Tehran
Postal code
۱۴۱۹۷۳۳۱۴۱
Phone
+98 21 6658 1624
Email
Rezaght@gmail.com
2
Recruitment center
Name of recruitment center
Barkat Cancer Specialist and Subspecialty Hospital
Full name of responsible person
Dr. Pedram Fadavi
Street address
Nasim 8th, Alimoradi Boulevard, Tehran
City
Tehran
Province
Tehran
Postal code
1485733186
Phone
+98 21 9200 1360
Email
fadavi.p@iums.ac.ir
3
Recruitment center
Name of recruitment center
Shohadaye Haftome Tir Hospital
Full name of responsible person
Dr Pedram Fadavi
Street address
at the end of South Shahid Rajaee Street,Tehran, Iran
City
Tehran
Province
Tehran
Postal code
11111111
Phone
+98 21 5522 8582
Email
fadavi.p@iums.ac.ir
4
Recruitment center
Name of recruitment center
Emam Hosein Hospital
Full name of responsible person
دکتر احمد رضازاده مافی
Street address
Shahid Madani St - Tehran - Iran
City
Tehran
Province
Tehran
Postal code
11111111111
Phone
+98 21 2273 9200
Email
ahmadrmafi@yahoo.com
5
Recruitment center
Name of recruitment center
Shahid Madani Hospital
Full name of responsible person
Dr Alireza Naseri
Street address
University Street, Tabriz
City
Tabriz
Province
East Azarbaijan
Postal code
111111111111
Phone
+98 21 3337 3900
Email
naseri47@yahoo.com
6
Recruitment center
Name of recruitment center
Golestan Hospital
Full name of responsible person
Dr Sasan Razmjoo
Street address
Golestan Alley - Farvardin Street
City
Ahwaz
Province
Khouzestan
Postal code
111111
Phone
+98 61 3374 3001
Email
razmjoo.md@gmail.com
7
Recruitment center
Name of recruitment center
Namazi Hospital
Full name of responsible person
Dr Mehdi Shariat
Street address
Zand Street, Namazi Square
City
Shiraz
Province
Fars
Postal code
7193613311
Phone
+98 71 3612 5000
Email
mahdyshr@gmail.com
8
Recruitment center
Name of recruitment center
Omid Hospital
Full name of responsible person
Dr Yasha Makhdomi
Street address
Kohsangi Street - Alandasht Square
City
Mashhad
Province
Razavi Khorasan
Postal code
11111111
Phone
+98 51 3842 6082
Email
makhdoumi@gmail.com
9
Recruitment center
Name of recruitment center
Shahid Ramezanzadeh Radiotherapy Center
Full name of responsible person
mohmmad ali boroumand
Street address
Shahid Motahari Street
City
Yazd
Province
Yazd
Postal code
11111111
Phone
+98 35 3725 1176
Email
m.h.baroomand@yazd.ac.ir
10
Recruitment center
Name of recruitment center
Emam Reza Hospital
Full name of responsible person
Dr Maliheh Dayani
Street address
End of Nurse Boulevard - Next to the Medical School
City
Kermanshah
Province
Kermanshah
Postal code
75333 - 67427
Phone
+98 83 3427 6300
Email
D.maliheh@gmail.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Zistdaru Danesh Co.
Full name of responsible person
Hooshmand Ilka
Street address
Unit 404, 4th Floor, Rosemal Building, Hemmet Expressway, Tehran, Iran
City
tehran
Province
Tehran
Postal code
1498711712
Phone
+98 21 4824 1000
Email
ilka@zistdaru.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Zistdaru Danesh Co.
Proportion provided by this source
100
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Industry
Person responsible for general inquiries
Contact
Name of organization / entity
Zistdaru Danesh Co.
Full name of responsible person
Zahra Rezagholi
Position
Medical department manager
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
Unit 404, 4th Floor, Rosemal Building, Hemmet Expressway, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1498711712
Phone
+98 21 4824 1000
Email
rezagholi.z@zistdaru.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr Farhad Samie
Position
Assistant Professor
Latest degree
Subspecialist
Other areas of specialty/work
Clinical Oncology
Street address
Number 260, west Fatemi street, Tehran
City
Tehran
Province
Tehran
Postal code
۱۴۱۹۷۳۳۱۴۱
Phone
+98 21 6643 5149
Email
samieifarhad@yahoo.com
Person responsible for updating data
Contact
Name of organization / entity
Zistdaru Danesh Co.
Full name of responsible person
Zahra Rezagholi
Position
Medical department manager
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
Unit 404, 4th Floor, Rosemal Building, Hemmet Expressway, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1498711712
Phone
+98 21 4824 1000
Email
rezagholi.z@zistdaru.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available