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CTRI Number  CTRI/2019/09/021256 [Registered on: 16/09/2019] Trial Registered Prospectively
Last Modified On: 23/09/2022
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Biological 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   A clinical trial to study the safety and efficacy of biosimilar cetuximab in patients with recurrent locoregional or metastatic squamous cell carcinoma of the head and neck. 
Scientific Title of Study   A prospective, multicenter, randomized, double blind, parallel group study to compare the efficacy and safety of biosimilar cetuximab versus innovator cetuximab in combination with platinum-based chemotherapy in patients with recurrent locoregional or metastatic squamous cell carcinoma of the head and neck (SCCHN).  
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
ALK18/ENZ124-CET1; v_02 Date: 27-Mar-2019  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Akhilesh Sharma 
Designation  President & Chief Medical Officer 
Affiliation  Alkem Laboratories Ltd 
Address  Alkem Laboratories Ltd. Unit no. 301, 3rd floor, Marathon Innovo, ‘B’ Wing, Opp. Peninsula Corporate Park, Ganpatrao Kadam Marg, Lower Parel (West), Mumbai, MAHARASHTRA-400013, India

Mumbai
MAHARASHTRA
400013
India 
Phone  022-39829999   
Fax    
Email  akhilesh.sharma@alkem.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Akhilesh Sharma 
Designation  President & Chief Medical Officer 
Affiliation  Alkem Laboratories Ltd 
Address  Alkem Laboratories Ltd. Unit no. 301, 3rd floor, Marathon Innovo, ‘B’ Wing, Opp. Peninsula Corporate Park, Ganpatrao Kadam Marg, Lower Parel (West), Mumbai, MAHARASHTRA-400013, India

Mumbai
MAHARASHTRA
400013
India 
Phone  022-39829999   
Fax    
Email  akhilesh.sharma@alkem.com  
 
Details of Contact Person
Public Query
 
Name  Dr Vinayaka Shahavi 
Designation  Associate General Manager, Clinical Research 
Affiliation  Alkem Laboratories Limited 
Address  Alkem Laboratories Ltd. Unit no. 301, 3rd floor, Marathon Innovo, ‘B’ Wing, Opp. Peninsula Corporate Park, Ganpatrao Kadam Marg, Lower Parel (West), Mumbai, MAHARASHTRA-400013, India

Mumbai
MAHARASHTRA
400013
India 
Phone  022-39829999  
Fax    
Email  vinayaka.shahavi@alkem.com  
 
Source of Monetary or Material Support  
Alkem Laboratories Limited, Alkem House, Senapati Bapat Marg,Lower Parel, Mumbai – 400 013, Maharashtra 
Enzene Biosciences Limited, Plot No. 165/1/26, Block T, Bhosari MIDC Area, Pune-411057, Maharashtra 
 
Primary Sponsor  
Name  Enzene Biosciences Limited 
Address  Enzene Biosciences Limited, Plot Number 165/1/26, Priyadarshani Society, Next to Gujjar Bharath gas) T 26, Internal Rd, MIDC, Bhosari, Pune, Maharashtra 411026 
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
Alkem Laboratories Limited  ALKEM HOUSE, “Devashish”, Adjacent to Matulya centre, Senapati Bapat Marg, Lower Parel west, Mumbai – 400013  
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 30  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Suhas Aagre  Aayush Hospital  102-1, 1st Floor, Laxman Arcade.Vivekanand Co-Op Hsg.Society ,90 feet Road, Dharavi, Mumbai -400017
Mumbai
MAHARASHTRA 
9638179565

suhas.aagre@gmail.com 
Dr Atul Sharma  All India Institute of Medical Sciences  All India Institute of Medical Sciences, Room No. 102, 1st Floor, Old O.T. Block, Ansari Nagar, New Delhi – 110 029, India
New Delhi
DELHI 
011-26589490

atul1@hotmail.com 
Dr SK Majumdar  All India Institute of Medical Sciences  All India Institute of Medical Sciences, Village Sijua, Patrapada, PO Dumduma, Bhubaneshwar – 751 019, Odisha, India
Khordha
ORISSA 
9438884066

sarojmajumdar@gmail.com 
Dr Pavithran Keechilat  Amrita Institue of Medical Science and Resrach Centre  Department of oncology and hematology, Amrita Institute of Medical Sciences, AIMS Ponekkara P O, Kochi- 682041
Ernakulam
KERALA 
9895367090

pavithrank@aims.amrita.edu 
Dr Shilpa Kandipalli  Andhra Medical College/King George Hospital  Department of Medical Oncology,Visakhapatnam – 530002, Andhra Pradesh, India
Visakhapatnam
ANDHRA PRADESH 
9440731463

shilpakandipalli@gmail.com 
Dr Chetan Deshmukh  Deenanath Mangeshkar Hospital & Research Center  Near Mhatre Bridge, Erandawne, Pune 411004, Maharashtra
Pune
MAHARASHTRA 
9850811449

chetandeshmukh72@gmail.com 
Dr Vijay Mahobia  Government Medical College  Government Medical College, Nagpur – 440 003, Maharashtra, India
Nagpur
MAHARASHTRA 
7122700266

drvijay_mahobia@yahoo.com 
Dr Rajnish Nagarkar  HCG Manavata Cancer Centre  HCG Manavata Cancer Centre, Mumbai Naka, Nashik – 422004, Maharashtra., India
Nashik
MAHARASHTRA 
9823061929

drraj@manavatacancercentre.com 
Dr Koushik Chatterjee  Health Point Hospital  Health Point Hospital, 21 Prannath Pandit Street, (Opposite Lansdown Puddapukur), Kolkata – 700 025, West Bengal, India
Kolkata
WEST BENGAL 
9874357580

drkoushik.chatterjee@gmail.com 
Dr Ravi Wategaonkar  Indrayani hospital and Cancer Institute  Narsimha Saraswati Medical Foundation, Alandi Devachi, Chakan Road, Taluka – Khed, Pune 412105, Maharashtra, India.
Pune
MAHARASHTRA 
9545496547

rnwategaonkar@gmail.com 
Dr Prasanth Ganesan  Jawaharlal Institute of Postgraduate Medical Education, Puducherry  Department of medical oncology, Jawaharlal Institute of Postgraduate Medical Education, Dhanvanti Nagar, Puducherry- 605006
Pondicherry
PONDICHERRY 
7736050004

drprasanthganesanresearch@gmail.com 
Dr Srikant Tiwari  Jawaharlal Nehru Cancer Hospital and Research Centre  P.B,No.32,Cancer hospital Rd, Idgah Hills, Bhopal-462001
Bhopal
MADHYA PRADESH 
9958783620

srikantabhinov@gmail.com 
Dr Minish Jain   KEM Hospital and Research Centre  KEM Hospital, Sardar Moodliar Road, 489 Rasta Peth, Pune-411 011 Maharashtra, India
Pune
MAHARASHTRA 
9823133390

minishjain009@gmail.com 
Dr Mahesh Kalloli  KLES Dr. Prabhakar Kore Hospital & M.R.C  Nehru Nagar, Belgavi-590010, Karnataka
Belgaum
KARNATAKA 
9945014996

mahesh.kalloli@gmail.com 
Dr Nilesh Dhamane  Kolhapur Cancer centre Pvt. Ltd.  Kolhapur Cancer center Pvt Ltd, R S 238, opp. Mayur petrol pump, Gokul Shirgaon, Kolhapur 416234
Kolhapur
MAHARASHTRA 
7738245698

dr.nilesh.gmc@gmail.com 
Dr Hemant Malhotra  Mahatma Gandhi Hospital  Department of Medical Oncology Mahatma Gandhi Medical College Hospital Mahatma Gandhi University of Medical Sciences and Technology Sitapura Jaipur
Jaipur
RAJASTHAN 
9892062040

drmalhotrahemant@gmail.com 
Dr Manu Prasad A  Malabar Cancer Center, Kannur  Department of Clinical Hematology & Medical Oncology, Malabar Cancer Centre, P.O Moozhikara, Thalassery, Kannur-670103
Kannur
KERALA 
4902355881

manuprasadmcc@gmail.com 
Dr Ananda Selva Kumar Pandy  Meenakshi Mission Hospital and Research Centre,  Lake Area, Melur Road, Madurai-625107
Madurai
TAMIL NADU 
9787713004

drask81@yahoo.co.in 
Dr PK Chaithanya  MNJ Institute of Oncology and Regional Cancer Centre  MNJ Institute of Oncology and Regional Cancer Centre, Red Hills, Lakidikapul, Near Niloufer Children Hospital, Hyderabad- 500 004, Telangana, India
Hyderabad
TELANGANA 
8897199994

chaitanyakrishna.medonc@gmail.com 
Dr Vashista Pankaj Maniar  Mumbai Oncocare Centre  2nd Floor , Majithia Apratments, God’s Gift Premises Co-op . society Ltd, S V Road, Irla, Vile Parle (W), Mumbai -400056
Mumbai
MAHARASHTRA 
9819834571

vpm@mocindia.co.in 
Dr Prakash SS  Mysore Medical college and Research Institute and K.R. Hospital  Mysore Medical college and Research Institute and K.R. Hospital, Irwin Road, Mysore – 570 001, Karnataka, India
Mysore
KARNATAKA 
9901000559

prakashyesyes@yahoo.com 
Dr Dhruv Pankaj Mehta  Nirmal Hospital  Ring road, Surat-395002
Surat
GUJARAT 
9727053929

dr.dhruv.mehta.14@gmail.com 
Dr B Ravi Shankar  Omega Hospitals  Chinna Gadhili, Hanumanthavaka, Vishakhapatnam-530040
Visakhapatnam
ANDHRA PRADESH 
9849123256

dr.bellalaravishankar@gmail.com 
Dr Rejnish Kumar  Regional Cancer Center  Department of Radiation Oncology, Regional Cancer Center, Medical College Campus, Post Box No. 2417, Trivandrum, Kerala, India 695011
Thiruvananthapuram
KERALA 
9447072333

rejnish@yahoo.com 
Dr Chandan Krushna Das  Regional Cancer Center, PGIMER, Chandigarh  Department of Radiotherapy & Oncology, Regional Cancer Centre, PGIMER (Post Graduate Institute of Medical Education and Research), Chandigarh, Sector 12, Pin Code-160012,INDIA
Chandigarh
CHANDIGARH 
9968846608

ckdasoncology@gmail.com 
Dr Kartar Singh  RST Regional Cancer Hospital and Research Center, Nagpur  RST Regional Cancer Hospital and Research Center, Manewada Road, Tukdoji Chowk, Nagpur 440027
Nagpur
MAHARASHTRA 
7020795655

drkartarsingh1972@gmail.com 
Dr Rohitashwa Dana  SMS Medical College and Hospital  Department- Surgery, SMS Medical College & Attached Hospital’s, J.L.N. Marg, Jaipur- 302001, Rajasthan Department of Radio-therapy, SMS Medical College and Attached Hospitals, J.L.N. Marg, Jaipur- 302001
Jaipur
RAJASTHAN 
9414129654

rdana2000@yahoo.co.in 
Dr Ambalathandi Ravi Chandran  Sri Ramachandra Medical College and Research Institute  Sri Ramachandra Medical College and Research Institute, No. 01, Ramachandra Nagar, Porur, Chennai– 600 116, Tamil Nadu, India
Chennai
TAMIL NADU 
9703436255

raviambalathandi@gmail.com 
Dr Sanjoy Chatterjee  Tata Medical Center, Kolkata  TATA Medical Center, 14 Major Arterial Road (EW), Newtown, Rajarhat, Kolkata- 700160
Kolkata
WEST BENGAL 
03366057403

sanjoy.chatterjee@tmckolkata.com 
Dr Kumar Prabhash  TATA Memorial Hospital   TATA Memorial Hospital, Dr. Ernest Borges Road, Parel Mumbai – 400 012, Maharashtras, India
Mumbai
MAHARASHTRA 
022-24176214

kprabhash1@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 31  
Name of Committee  Approval Status 
DMH Institutional Ethics Committee  Approved 
Ethics Committee, Unique Hospital- Multispecialty & Research Institute  Approved 
HCG Manavata Clinical Research Institutional Ethics Committee  Approved 
HCG Mulitispeciality Ethics Committee, Ahmadabad  Approved 
Health Point Hospital Ethics Committee  Approved 
Human Ethics Committee, Trivandrum  Submittted/Under Review 
Institute Ethics Committee, All India Institute of Medical Sciences, Delhi  Approved 
Institutional Ethics Committee of Aayush Hospital  Approved 
Institutional Ethics Committee, AIIMS Bhubaneshwar  Approved 
Institutional Ethics Committee, Amrita Institute of Medical Sciences, Kochi  Submittted/Under Review 
Institutional Ethics Committee, Government Medical College  Approved 
Institutional Ethics Committee, JIPMER, Puducherry  Approved 
Institutional Ethics Committee, Kerala  Approved 
Institutional Ethics Committee, King George Hospital  Approved 
Institutional Ethics committee, Mahatma Gandhi Medical College and Hospital  Approved 
Institutional Ethics Committee, Omega Hospitals  Approved 
Institutional Ethics Committee, PGIMER, Chandigarh  Approved 
Institutional Ethics Committee, RST Regional Cancer Center, Nagpur  Approved 
Institutional Ethics Committee, TATA Medical Center, Kolkata  Approved 
Institutional Ethics Committee, TATA Memorial Hospital  Approved 
KEM Hospital Research Centre Ethics Committee  Approved 
KLES Dr. Prabhakar Kore Hospital & M.R.C., IEC  Approved 
Kolhapur Cancer Centre Institutional Ethics Committee  Approved 
Meenakshi Mession Hospital, IEC  Approved 
MNJ Institute of Oncology & Regional Cancer Centre Ethics Committee  Approved 
Mumbai Oncocare Centre Institutional Ethics Committee  Approved 
Mysore Medical college and Research Institute and K.R. Hospital  Approved 
Nirmal Hospital Ethics Committee  Approved 
SMS medical college, IEC  Approved 
Sri Narsimha Saraswati Medical Foundation Ethics Committee  Approved 
Sudhbhawana Hospital, IEC  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C148||Malignant neoplasm of overlappingsites of lip, oral cavity and pharynx,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Biosimilar Cetuximab  Dosage Form: It will be supplied in concentration of 5 mg/mL as a 100 mg/20 ml single-use vial, as a sterile, injectable liquid containing no preservatives. Dosage: The initial dose is 400 mg per m2 to be administered as an IV infusion over a period of 120 mins, subsequently Cetuximab shall be administered at a dose of 250 mg per m2 per week(visit 2 to visit18) as an IV infusion over a period of 60 minute 
Comparator Agent  Innovator Cetuximab  Dosage Form: It will be supplied in concentration of 5 mg/mL as a 100 mg/20 ml single-use vial, as a sterile, injectable liquid containing no preservatives. Dosage: The initial dose is 400 mg per m2 to be administered as an IV infusion over a period of 120 mins, subsequently Cetuximab shall be administered at a dose of 250 mg per m2 per week(Cycle 2 to Cycle 18) as an IV infusion over a period of 60 minutes.  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1.Patients of 18-65 years of age at the time of signing the ICF
2.Has life expectancy of at least 6 months from screening
3. Histologically confirmed diagnosis of SCCHN
4. Presence of recurrent locoregional (not suitable for local therapy) or metastatic disease as per Tumor Node Metastasis staging at screening
5. In case of recurrent locoregional carcinoma, patients must have documented progression of platinum-based chemotherapy for recurrent disease
6. Has at least 1 measurable target lesion (tumor/lymph node) as per RECIST version 1.1 at screening
7. Eastern cooperative oncology group (ECOG) status 0 to 2 at screening
8. Willing and able to comply with the protocol
9. Willing to provide written informed consent 
 
ExclusionCriteria 
Details  1.Patients with Nasopharyngeal cancer
2.Prior systemic chemotherapy (except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to screening)
3.Patient who has received cetuximab or other EGFR targeting agent treatment (except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to screening)
4.Surgery (other than minor interventions like diagnostic biopsy or intravenous port implantation) or irradiation within 30 days before randomization
5.Concomitant anti-tumor therapy or concomitant immunotherapy
6.Known sensitivity to any component of the investigational product (IP) and medication used in this study
7.Clinical evidence of brain metastasis or leptomeningeal involvement
8.History of Interstitial Lung Disease
9.History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies
10.Patient’s having the following laboratory results at screening
a.Absolute neutrophil count (ANC) < 1,500/mm3
b.Hemoglobin (Hb) < 9 g/dL
c.Total Leucocyte count < 3000/mm3
d.Platelet count < 100,000/mm3
e.Total bilirubin level > 1.5 times the upper limit of the normal laboratory range (ULN)
f. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels ≥ 5 times ULN
g.Serum Creatinine level > 1.5 times ULN
h.Abnormal serum electrolytes (within normal limit)
i. INR and aPTT (within normal limit)
11.Patients suffering from acute or chronic infection(s)
12.Myocardial infarction within 6 months prior to screening
13.Symptomatic congestive heart failure (New York Heart Association [NYHA] Grade 3 or 4), unstable angina pectoris within 6 months prior to screening, significant cardiac arrhythmia, history of stroke or transient ischemic attack within 1 year prior to screening
14. Pre-existing grade 2 or greater motor or sensory neuropathy
15. Active hemoptysis (defined as bright red blood of ½ teaspoon or more in saliva) within 30 days prior to randomisation.
16.History of clinically significant gastrointestinal bleeding (bleeding requiring procedural intervention (e.g., variceal banding, transjugular intrahepatic portosystemic shunt procedure, arterial embolization, topical coagulation therapy) within 6 months prior to randomisation.
17.Patients with history of keratitis
18.Positive serology for human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) at screening
19.Female patients of childbearing potential not willing to implement adequate non-hormonal contraceptive measures during the study period
20.Patients who are pregnant or nursing
21.Has any concurrent disease or condition, which in the opinion of the investigator does not allow participation of the patient in this study
22.Has participated in any other clinical trial and received experimental medications within 4 weeks prior to screening. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded 
Primary Outcome  
Outcome  TimePoints 
1. To compare the efficacy of biosimilar cetuximab versus innovator cetuximab in patients with recurrent locoregional or metastatic SCCHN by assessment of Disease Control
Rate (DCR)
2.To compare the efficacy of biosimilar cetuximab versus innovator cetuximab in patients with recurrent locoregional or metastatic SCCHN by assessment of overall response
rate (ORR)  
1. All patients completed 12 week of treatment
2. All patients completed 18 weeks of treatment 
 
Secondary Outcome  
Outcome  TimePoints 
1. Pharmacokinetics (PK) of biosimilar versus innovator cetuximab
2.Immunogenicity of biosimilar cetuximab and innovator cetuximab by assessment of
anti-cetuximab antibody (ADA)
 
Anti-cetuximab antibody (ADA): baseline and Week 18 visit
PK Assessment:Baseline, Week2,3 and 4
 
 
Target Sample Size   Total Sample Size="180"
Sample Size from India="180" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   30/10/2019 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Closed to Recruitment of Participants 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary   The primary and secondary purpose behind conducting this trial are: 1. To compare the efficacy of biosimilar cetuximab versus innovator cetuximab in patients with recurrent locoregional or metastatic SCCHN by assessment of Disease Control Rate (DCR) and Overall Control Rate (ORR) 
2. To compare Pharmacokinetics (PK) of biosimilar versus innovator cetuximab, immunogenicity of biosimilar cetuximab and innovator cetuximab by assessment of anti-cetuximab antibody, safety and tolerability of the investigational product.
 
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