CTRI/2022/12/047923 [Registered on: 06/12/2022] Trial Registered Prospectively
Last Modified On:
13/04/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A Phase III, Study to Investigate the Efficacy, Safety, and Pharmacokinetics of ZRC-3276 Versus Opdivo® (Nivolumab) in Subjects with locally advanced or Metastatic Non-Small Cell Lung Cancer
Scientific Title of Study
A Phase III, Prospective, Randomized, Multicenter,
Comparative, Double blind, Parallel-group Study to
Investigate the Efficacy, Safety, and Pharmacokinetics
of ZRC-3276 Versus Opdivo® (Nivolumab) in Subjects
with locally advanced or Metastatic Non-Small Cell
Lung Cancer
Department of Medical Oncology, Room No. 160-A, First Floor, All India Institute of Medical Sciences (AIIMS), Dr. B.R. Ambedkar Institute Rotary Cancer Hospital, Ansari Nagar, New Delhi 110029, India
New Delhi DELHI
Basavatarakam Indo- American cancer hospital & research institute
Dept of Medical Oncology, Basavatarakam Indo- American cancer hospital & research institute, Road No 10, Banjara hills, Hyderabad- 500034
Hyderabad TELANGANA
9866154503 91-40-23542120 mvtkm@yahoo.com
Dr Bidisha Ghosh
Charnock Hospital
Charnock Hospital, Building No 4, OPD Section, Ground Floor BMC 195, Teghoria, Biswas Bangla Sarani, Kolkata -700157,
Kolkata WEST BENGAL
9432164842
bghoshn@gmail.com
Dr Chetan Deshmukh
Deenanath Mangeshkar Hospital & Research Center
Deenanath Mangeshkar Hospital & Research Center, Erandwane, Pune, Maharashtra 411004
Pune MAHARASHTRA
9850811449 2040151000 drchetandeshmukh@gmail.com
Dr KLakshmi Priyadarshini
HCG Curie City Cancer Center
HCG Curie City Cancer Center, 33-25-33, Gopala Krishnaiah St, Suryaraopeta, Vijayawada, Andhra Pradesh- 520002 Krishna ANDHRA PRADESH
9966030988 08662430871 priyadarshini006@gmail.com
Dr Rajnish Nagarkar
HCG Manavata Cancer Center
HCG Manavata Cancer Center, B/H Shivang Auto, Mumbai Naka, Nashik, Maharashtra- 422002 Nashik MAHARASHTRA
K R Hospital.Mysore Medical College & Research Institute
K R Hospital.Mysore Medical College & Research Institute,Irwin Road,Mysore-570001,Karnataka,India
Mysore KARNATAKA
9901000559
prakashyesyes@yahoo.com
Dr Santhosh Vandanasetti
Kailash Cancer Hospital & Research Center
Kailash Cancer Hospital & Research Center, Muniseva Ashram, Goraj, Waghodia, Vadodara-391760
Vadodara GUJARAT
9427423693
vandanasetti.santhosh@greenashram.org
Dr Yatish Kumar
Karnataka Cancer Center
"Karnataka Cancer Center,
No: 99, Kanteerava Studio Main Road,
Krishnanandana Nagar, Yeswanthpur,
Bengaluru, Karnataka -560096, India"
Bangalore KARNATAKA
Clincial Research department,Room No. 201,Life line diagnostic centre cum nursing home; 4A, Woodstreet, Kolkata-700016, West Bengal, India
Kolkata WEST BENGAL
9874357580
drkoushik.chatterjee@gmail.com
Dr Rajani Priya Yedla
Mahatma Gandhi Cancer Hospital & Research Institute
Medisquare Superspeciality Hospital And Research Institue
"MediSquare Superspeciality Hospital and Research Institute,
O-201, 202, Gala Empire, Drive in Rd,
opp Doordarshan Tower, Gurukul, Ahemedabad , Gujarat-380052
"
Ahmadabad GUJARAT
8238034088
ektavala89@gmail.com
Dr Parimkayala Radhika
MNJ Institute of Oncology & Regional Cancer Center
3rd Floor, Clinical Trial Room No. 11, Red Hills, Hyderabad, Telangana-500004 Hyderabad TELANGANA
"Sri Aurobindo Institute of Medical Sciences.
Indore. Madhya Pradesh. 453555"
Indore MADHYA PRADESH
9972374987
vikas1asati@gmail.com
Dr KCLakshmaiah
Srinivasam Cancer Care Multispeciality Hospital India Pvt. Ltd.
No.36, 1st A main Road,
5th cross Maruthinagar,
Nagarbhavi Main Road,
Bangalore, Karnataka- 560072 Bangalore KARNATAKA
919448055947
kcluck@gmail.com
DrRicha Madhawi
State Cancer Institute, Indira Gandhi Institute of Medical Sciences
State Cancer Institute, Indira Gandhi Institute of Medical Sciences,Sheikhpura,Patna, Bihar 800014
Patna BIHAR
9431186988 06122297225 drricha.madhawi@yahoo.in
Dr Aditi Harsh Thanky
Sterling Hospital
Unit of Sterling Add-life India Pvt. Ltd. Plot No 251, 150 Feet Ring Road, Nr. Raiya Circle, Rajkot- 360007, Gujarat, India
Rajkot GUJARAT
9925025381
aditik2008@yahoo.com
Dr Neha Gupta
Swami Harshankaranand Ji Hospital & Research Center
wami Harshankaranand Ji Hospital & Research Center, N8/237, BHU Road, Near Bhikaripur Crossing, Opposite Union Bank of India, BHU, Sundarpur, Newada, Varanasi, Uttar Pradesh 221005, India
Varanasi UTTAR PRADESH
8004354185
drneha_500@yahoo.com
Dr Rakesh Taran
Taran Onco Care (A Unit of Taran Medi care pvt Ltd)
" Institute Ethics Committee All India Institute of Medical Sciences Old OT Block, Room No. 102, AIIMS Hospital Ansari Nagar, New Delhi-29 New Delhi South Delhi Delhi - 110029 India"
Approved
"Ethics Committee S.M.S. Medical College and Attached Hospitals J.L.N. Marg Jaipur Jaipur Jaipur Rajasthan - 302004 India"
Approved
"ETHICS COMMITTEE, SANJEEVANI CANCER HOSPITAL SANJEEVANI CBCC USA CANCER HOSPITAL FRONT OF JAIN MANDIR DAWADA COLONY PACHPEDI NAKA RAIPUR Raipur Chhattishgarh - 492001 India"
"Saroj Gupta Cancer Centre and Research Institute 109 Mahatma Gandhi Road Thakurpukur Kolkata South 24 Parganas West Bengal - 700063 India "
Approved
"SCCMH- IEC Srinivasam Cancer Care Multispeciality Hospital No. 36 1 ST A Main 5th Cross Nethravthi, Street MaruthiNagar, Bengaluru (Bangalore) Urban, Karnataka- 560072 "
HCG Central Ethics Committee HCG- Bangalore institute of Oncology HCG Towers, Tower-I P. Kalinga Rao Road, Sampangiram Nagar Bangalore Bengaluru (Bangalore) Urban Karnataka - 560027 India
Approved
Institutional Ethics Committee Sparsh Hospitals and Critical Care Private Limited Plot No-A/407, Saheed Nagar, Bhubaneswar Khordha, Orissa - 751007 India
Approved
Institutional Ethics Committee HCG Cancer Centre HCG Cancer Centre Plot No 10, APIIC Health City, Arilova Chinnagadili, Mudasarlova Road Visakhapatnam Visakhapatnam Andhra Pradesh - 530040 India
Approved
INSTITUTIONAL ETHICS COMMITTEE HUMAN GOKUL LIFECARE PRIVATE LIMITED 12/14 MANHAR PLOT VINDHYANAGAR MAIN ROAD RAJKOT Rajkot Gujarat - 360001 India
Approved
Institutional Ethics Committee Kailash Cancer Hospital & Research Centre, , Goraj- 391760, Waghodia, Vadodara, India.
Approved
Institutional Ethics Committee of OCH and RC Oncoville Cancer Hospital And Research Centre No.4, 80 Ft. Road, 7th Block , Nagarbhavi 2nd Stage Bengaluru Urban Bengaluru (Bangalore) Urban Karnataka - 560072 India
Approved
Institutional Ethics Committee Sarvodaya Hospital & Research Centre (A Unit of Anshu Hospitals Limited, YMCA Road, Sector-8, Faridabad (India)- 121006, India
Approved
Institutional Ethics Committee Valentis Cancer Hospital Mussoorie Mawana Road Meerut Meerut Meerut Uttar Pradesh - 250001 India
Approved
Institutional Ethics Committee, department of Community Medicine, Room No:01, Second floor, college Building BGS Global Institute of Medical Sciences 67 BGS Health and Education City Uttarahalli Road Kengeri Bangalore South Karnataka Bengaluru( Bangalore) Urban Karnatak-560060 India
Approved
Institutional Ethics Committee, IGIMS ,Sheikhpura Indira Gandhi Institute Of Medical Sciences Sheikhpura Raja Bazar Patna Patna Bihar - 800014 India
Approved
Institutional Ethics Committee, Life line diagnostic centre cum nursing home; 4A, Woodstreet, Kolkata-700016, West Bengal, India
Approved
Institutional Ethics Committee, PGIMS UHS Rohtak Pt. BD Sharma, Post Graduate Institute Of Sciences PGIMS UHS Rohtak-124001 Rohtak Rohtak Haryana
Approved
Institutional ethics committee, SAMC & PGI ,Sri Aurobindo Institute of Medical Sciences. Indore. Madhya Pradesh. 453555
Approved
Institutional Ethics Committee- HCG CURIE CITY CANCER CENTRE 44-1-1/3 Padavalarevu, Gunadala Vijayawada Krishna Andhra Pradesh - 520004 India
Approved
INSTITUTIONAL REVIEW BOARD MAHATMA GANDHI CANCER HOSPITALRESEARCH INSTITUTE 1-7 MVP COLONY VISAKHAPATNAM Visakhapatnam Andhra Pradesh - 530017 India
Approved
K R Hospital.Mysore Medical College & Research Institute,Irwin Road,Mysore-570001,Karnataka,India
Approved
KD Hospital Institutional Ethics Committee K D Hospital Ahmedabad KD Hospital Vaishnavdevi Circle, S.G.Highway, Khodiar, Ta. Dascroi, Dist. Ahmedabad Ahmedabad Ahmedabad Gujarat - 382421 India
(1) ICD-10 Condition: C349||Malignant neoplasm of unspecifiedpart of bronchus or lung,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Opdivo (Bristol-Myers Squibb)
Dose :- 3 mg/kg
Route :- IV infusion
Frequency :- every 14 day Duration :- 6 month
Intervention
ZRC-3276 (Cadila Healthcare Ltd.)
Dose :- 3 mg/kg
Route :- IV infusion
Frequency :- every 14 day Duration :- 6 month
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1.Male or female with≥ 18 years of age
2.Subjects with histologically or cytologically-documented locally advanced or metastatic NSCLC who present with Stage IIIB/IIIC/Stage IV or recurrent or progressive disease following multi-modality therapy (radiation therapy, surgical resection or definitive chemo radiation therapy for locally advanced disease).
Note: Subjects eligible for study therapy after acceptable prior therapy are as specified
below:
o Subjects must have experienced disease recurrence or progression during or after one first line therapy for advanced or metastatic disease.
o A switch of an agent within a regimen in order to manage toxicity does not define the start of a new line of therapy. Subjects must have received at least 2 cycles of platinum doublet based chemotherapy before discontinuation for toxicity.
o Maintenance therapy following first line chemotherapy is not considered as a separate regimen of therapy and could comprise continuation of one or more of the agents used in the first-line therapy regimen or switch to another non cross-resistant agent. The initiation of maintenance therapy requires the lack of progressive disease with front-line therapy. Subjects who showed disease progression during or after maintenance therapy will be eligible.
o Treatment given for locally advanced disease is not considered as a line of therapy for advanced disease. Participants with recurrent disease >6 months after platinum containing adjuvant, neoadjuvant or definitive chemo-radiation therapy given for locally advanced disease, who also subsequently progressed during or after a platinum doublet-based regimen given to treat the recurrence,
are eligible.
o Experimental therapies when given as separate regimen are considered as separate line of therapy. Subject who received experimental therapies for disease progression after fist line therapy will not be eligible.
- Participants who received adjuvant, neoadjuvant chemotherapy or definitive chemo-radiation therapy given for locally advanced disease, and developed recurrent disease within 6 months of completing therapy are eligible.
o Adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) followed by recurrent or metastatic disease within 6 months of completing therapy is considered as first line therapy for advanced disease.
3.With at least one measurable target lesion (based on response evaluation criteria in solid tumors [RECIST] criteria, version 1.1) performed within 28 days of randomization
a. Target Lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site
4.Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1.
5. Subjects who meets following laboratory values (assessed within 28 days prior to randomization):
a. WBCs ≥2000/μL
b. Neutrophils ≥1500/μL
c. Platelets ≥100 X 10³/μL
d. Hemoglobin ≥9.0 g/dL
e. Serum creatinine of ≤1.5 X ULN or creatinine clearance >40 mL/minute (using Cockcroft/Gault formula)
f. AST & ALT ≤1.5 X ULN
g. Total bilirubin ≤ 1.5 X ULN
6. Female subjects who are not pregnant or breastfeeding and at least one of the following conditions applies:
-Are postmenopausal for at least 24 months before the screening visit, OR
-Are surgically sterile by bilateral tubal ligation, hysterectomy, or bilateral oophorectomy, OR
-If they are of childbearing potential, agree to practice highly effective methodsof contraception (failure rate of less than 1% per year) with low user dependency when used consistently and correctly, from at least 28 days before
starting study drug through 5 months after the last dose of study treatment, OR agree to completely abstain from heterosexual intercourse
- A woman of child bearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin (beta-hCG) test at Screening and urine beta-hCG test at Baseline
7.Male subjects, even if surgically sterilized (i.e., status post vasectomy), who:
-Agree to completely abstain from heterosexual intercourse, OR
-Agree to practice effective barrier contraception during the entire study treatment period and through 5 months after the last dose of study treatment if their partner is of childbearing potential, even if they have had a successful vasectomy.
8.No clinically significant findings on clinical and/or physical examination, 12 lead ECG, or laboratory tests after signing the ICF but before receiving the first dose study drug. The Investigator will determine if a particular finding is clinically significant.
9. Subjects must have signed and dated an Institutional Review Board (IRB)/ Independent Ethics committee (IEC) approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
10. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study
ExclusionCriteria
Details
1. Subjects with CNS metastases, except for treated asymptomatic CNS metastases, provided all of the following criteria are met:
a. Only supra-tentorial metastases allowed (i.e., no metastases to midbrain,
pons, medulla, or spinal cord)
b. No evidence of interim progression or hemorrhage after completion of
CNS-directed therapy
c. No ongoing requirement for corticosteroids as therapy for CNS disease
(anticonvulsants at a stable dose are allowed at least two weeks prior to
screening)
d. No stereotactic radiation within 14 days or whole-brain radiation within 28
days prior to randomization
e. Leptomeningeal disease (i.e. carcinomatous meningitis)
2.History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti- HCV at Screening.
3. History of human immunodeficiency virus (HIV) antibody positive, or tests
positive for HIV at Screening.
4. Other active malignancy requiring concurrent intervention.
5. Subject with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, cervical/dysplasia, endometrial, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to screening AND no additional therapy is required or anticipated to be required during the study period.
6. Subject with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Corticosteroids with minimal systemic absorption and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
7. Subject with active, known or suspected autoimmune disease. Subject with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin
disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
8. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue not resolved to grade 1 (NCI CTCAE version 5) or baseline before
administration of study drug.
9. Prior therapy with anti-tumor vaccines or other immuno-stimulatory antitumor
agents.
10. Prior radiotherapy or radiosurgery received within 2 weeks prior to screening.
11. Prior treatment with Nivolumab or any other anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CD-137, or anti-CTLA-4 antibody (including ipilimumab or any other
antibody or drug specifically targeting T-cell co-stimulation or checkpoint
pathways)
12. Subject with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
13. Subject not recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment.
14. History of severe hypersensitivity reactions to other monoclonal antibodies.
Allergy or intolerance (unacceptable adverse event) to study drug components, or
Polysorbate-80-containing infusions.
15. Ongoing or planned administration of anti-cancer therapies other than those
specified in this study or use of strong CYP3A4 inhibitors.
16. Have received treatment with any other investigational drug in the last 30 days before study entry, or within less than five half-lives after receiving the previous investigational drug.
17. Receipt of IV antibiotics for infection within 14 days of randomization.
18.Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment.
19. Current severe, uncontrolled systemic disease (e.g., clinically significant
cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers;
or bone fractures).
20. Have a history or suspicion of unreliability, poor cooperation or non-compliance with medical treatment or any other medical or psychiatric condition that could compromise study participation.
21. History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 1 year before Screening or positive test result(s) for alcohol or drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines) at Screening if required as per medical history.
22. Have any concurrent disease or condition that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Compare the efficacy of
ZRC-3276 IV infusion versus
Opdivo IV infusion in subjects
with locally advanced or
metastatic non-small cell lung
cancer.
Baseline and Cycle 12
Secondary Outcome
Outcome
TimePoints
To assess the pharmacokinetics
of ZRC-3276 IV infusion
compared to Opdivo IV
infusion
Cycle 1 for various PK parameters
and trough concentration evaluation at
pre-dose of Cycle 4, 6, 8, 10, 12, and at
EOS
To assess the immunogenicity
of ZRC-3276 IV infusion
compared to Opdivo IV
infusion
Baseline, end of Cycle 6 (pre-dose
of Cycle 7), and end of Cycle 12 (EOS)
To compare the safety and
tolerability in subjects exposed
to the investigational medicinal
products
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Lung cancer is the most common cancer and the leading cause of cancer-related deaths globally. Non–small-cell lung cancer accounts for 85% to 90% of lung cancers . Based on the national cancer registry data, incidence of lung cancer is highest amongst all approved indication of Nivolumab in India. Therefore, the selection of target patient population for current study was based on data in Indian population.
Nivolumab is a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, that binds with high affinity to PD-1 receptors expressed on T cells and disrupts negative signaling induced by PD-ligand 1 (PD-L1) and PD-ligand 2 to restore T-cell effector function. In one of the Phase I study in patients with advanced NSCLC, Nivolumab monotherapy demonstrated a mean ORR of 17% and 18% in pateints with squamous and nonsquamous histologies, respectiely. The survival rates were 42% (95% CI, 33 to 50) at 1 year, 24% (95% CI, 17 to 33) at 2 year, and 18% (95% CI, 11 to 25) at 3 year in the total population across all dose levels. [13]. These initial signals of efficacy and tolerability prompted two phase
III trials that demonstrated a survival benefit for salvage Nivolumab over docetaxel in patients with advanced pretreated NSCLC leading to its approval in the United States for treatment of patients with metastatic NSCLC whose disease has progressed on or after platinum based chemotherapy and after an approved TKI therapy (if expressing EGFR or ALK genomic tumor aberrations). Also, Nivolumab is approved in the European Union for locally
advanced or metastatic NSCLC after prior chemotherapy.