CTRI/2022/05/042823 [Registered on: 26/05/2022] Trial Registered Prospectively
Last Modified On:
16/02/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Study To Test The Usage of Denosumab In Patients with Cancer spread to Bone
Scientific Title of Study
A Randomized, Multiple-dose, Multicenter, Comparative Parallel Study to Evaluate the
Pharmacokinetic, Pharmacodynamic, Efficacy and Safety of Subcutaneous Injection of
Denosumab (Hetero) and Reference Medicinal Product (Denosumab, Amgen Inc.) in patients
with bone metastases from solid tumors.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
HCR/III/DENOSOL/12/2019 Version 1.0 Date 03Dec2019
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Dr Sreenivasa Chary S
Designation
General Manager
Affiliation
Hetero Drugs Limited
Address
Clinical Development and Medical Affairs, 2nd Floor, 7-2-A2, Hetero Corporate, Industrial Estates, Sanath Nagar
Hyderabad TELANGANA 500018 India
Phone
04023704923
Fax
Email
sreenivasa.chary@heterodrugs.com
Details of Contact Person Public Query
Name
Dr Shubhadeep Sinha
Designation
Sr. Vice President
Affiliation
Hetero Drugs Limited
Address
Clinical Development and Medical Affairs, 2nd Floor, 7-2-A2, Hetero Corporate, Industrial Estates, Sanath Nagar
Hyderabad TELANGANA 500018 India
Phone
040-23704923
Fax
040-23801902
Email
sd.sinha@heterodrugs.com
Source of Monetary or Material Support
Hetero Biopharma Limited, H. No. 8-3-166/1,2, 105 to 108, 1st Floor, G Block, East Wing, Challa Estates, Erragadda, Hyderabad, Telangana, India, 500018. Tel No. and Fax No.: 914023810110
Primary Sponsor
Name
Hetero Biopharma Limited
Address
Hetero Biopharma Limited, H. No. 8-3-166/1,2, 105 to 108, 1st Floor, G Block, East Wing, Challa Estates, Erragadda, Hyderabad, Telangana, India, 500018. Tel No. and Fax No.: 914023810110
Institute of Post Graduate Medical Education & Research (IPGME&R)
Institution of Post Graduate Medical Education & Research, Ground floor Room no 15 244 AJC Bose Road, Kolkata- 700020, West Bengal, India Kolkata WEST BENGAL
7980253154
suparna.k.pal@gmail.com
Dr Mithun Chacko John
Jubilee Mission Medical College and Research Institute
Department of Medical Oncology, Gut No.43, Satara Parisar, Beed Bypass Road,
Aurangabad-431010 Aurangabad MAHARASHTRA
9901835738
abhinav.zawar@gmail.com
Dr Vijay Kumar
King Georges Medical University
Department of Surgical Oncology, 3rd Floor Shatabdi Phase 2, Chowk, Lucknow - 226003 Lucknow UTTAR PRADESH
9935383666
drvkumar2007@gmail.com
Dr Nilesh Ashok Dhamne
Kolhapur Cancer Centre Pvt Ltd
Ist floor , CRC Department R.S.238, Opp. Mayur petrol pump, Gokul Shirgaon, Kolhapur-416234, Maharashtra Kolhapur MAHARASHTRA
7738245698
dr.nileshgmc@gmail.com
Dr Praveen Kumar Shenoy VP
Malabar Cancer Center
Department of Clinical Hematology and Medical Oncology, P.O. Moozhikkara, Thalassery, Kannur- 670103 Kannur KERALA
9778425561
vppraveen233@gmail.com
Dr Kirushna Kumar Kosanam Subramanian
Meenakshi Mission Hospital & Research Centre
Department of Oncology, Lake Area, Melur Road, Madurai-625107 Madurai TAMIL NADU
9842113003
drkskk@yahoo.com
Dr P Radhika
MNJ Institute of Oncology and Regional Cancer Centre
Room No:4, 3rd Floor, Red hills, Hyderabad-500004 Hyderabad TELANGANA
9848792682
radhika.parimkayala@gmail.com
Dr Kshitij Joshi
Mumbai Oncocare centre (A Unit of Cellcure Cancer CentrePvt Ltd)
Mumbai Oncocare centre (A Unit of Cellcure Cancer Centre Pvt Ltd), 2nd floor, Majithia Apartments, Gods Gift Premises Co-op Society Ltd, Above Irla Nursing Home, S V road, Ville Parle West, Mumbai-400056 Mumbai MAHARASHTRA
Clinical Research Room, 2nd Floor, Medical College-Baroda, Jail Road (Indira Avenue), Vadodara, Gujarat-390001 Vadodara GUJARAT
9426367470
dryamini_patel@yahoo.com
Dr Ravindra Singh Gothwal
SMS Medical College & Hospital
Department of Radiation Oncology, Room No. 46, Fourth Floor, Dhanvantri OPD Block, Jaipur-302004 Jaipur RAJASTHAN
9887038220
drravindragothwal@yahoo.com
Dr Ghanashyam Biswas
Sparsh Hospitals and Critical Care (P) Ltd
Dept of Radiotherapy, A/407 Saheed Nagar, Bhubaneswar-751007 Khordha ORISSA
9937500878
drgbiswas@gmail.com
Dr Ankur Punia
Sri Ram Cancer and Superspeciality Centre, Mahatma Gandhi medical College and Hospital
Department of Oncology, A unit of Mahatma Gandhi University of Medical Sciences and Technology, Sitapura, Tonk Road, RIICO institutional area, Jaipur-302022 Jaipur RAJASTHAN
9799777785
drankurpunia@gmail.com
Dr K C Lakshmaiah
Srinivasam Cancer Care Multispeciality Hospitals India Pvt Ltd
Srinivasam Cancer Care Multispeciality Hospitals India Pvt Ltd, No. 36, 1st A Main Road, 5th Cross, Nethravathi St, Maruthi Nagar, Nagarbhavi Main Road, Bangalore-560072. Bangalore KARNATAKA
9448055949
kcluck@gmail.com
Dr VM Durai Mavalavan
SRM Medical College Hospital and Research Centre
Department of Oncology, Kattankulathur- 603203, Chengalpattu Kancheepuram TAMIL NADU
9941702373
dmavalavan@yahoo.co.in
Dr Ankit Batra
Swami Rama Himalayan Institute of Medical Sciences
Cancer Research Institute, Himalayan Institute of Medical Sciences, Swami Rama Nagar, Jolly Grant, Dehradun- 248016 Dehradun UTTARANCHAL
9411712969
drankitbatra@gmail.com
Dr Sandip Ganguly
Tata Medical Center
Tata Medical Center, 14 Major Arterial Road (E-W) DH Block (New town), Action area I, New town, Rajarhat, Kolkata, West Bengal-700160 Kolkata WEST BENGAL
9663667459
dr.babumashai@gmail.com
Dr Ankit Patel
Unique Hospital Multispeciality and Research Institute
Opp. Kiran Motors, Near Canal, Civil Char Rasta, Sosyo Circle Lane, Off Ring Road, Surat - 395002 Surat GUJARAT
9825404202
drankitoncologist@gmail.com
Dr Kaushal Kalra
Vardhman Mahavir Medical College and Safdarjung Hospital
Vardhman Mahavir Medical College and Safdarjung Hospital, Department of Medical Oncology, New Delhi-110029 New Delhi DELHI
Institutional Ethics Committee HCG Curie City Cancer Centre
Approved
Institutional Ethics Committee Jubilee Mission Medical College and Research Institute
Approved
Institutional Ethics Committee King Georges Medical University
Approved
Institutional Ethics Committee Mahatma Gandhi medical College and Hospital
Approved
Institutional Ethics Committee Meenakshi Mission Hospital & Research Centre
Approved
Institutional Ethics Committee North East Cancer Hospital and Research Institute
Approved
Institutional Ethics Committee SMS Medical College & Hospital
Approved
Institutional Ethics Committee SRM Medical College Hospital
Approved
Institutional Ethics Committee Unique Hospital Multispeciality and Research Institute
Approved
Institutional Ethics Committee VMMC and SJH VMMC and Safdarjung Hospital
Submittted/Under Review
Institutional Ethics Committee, Bhagwan Mahaveer Cancer Hospital and Research Center
Submittted/Under Review
Institutional Ethics Committee, Chittaranjan National Cancer Institute
Submittted/Under Review
Institutional Ethics Committee, Indira Gandhi Institute of Medical Sciences
Approved
Institutional Ethics Committee, Malabar Cancer Centre
Approved
IPGMEandR Research Oversight Committee, IPGMEandR
Approved
KCC Institutional Ethics Committee Kolhapur Cancer Centre Pvt. Ltd.
Submittted/Under Review
Magna Care Ethics Committee
Approved
Mumbai Oncocare Centre IEC
Submittted/Under Review
Omega Ethical Committee
Approved
SCCMH-Institutional Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C795||Secondary malignant neoplasm of bone and bone marrow,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Injection Hetero-Denosumab
Injection: 120 mg/1.7 mL (70 mg/mL) solution in a single dose
vial every 4 weeks for 24 weeks
Comparator Agent
Injection Reference-Denosumab (Amgens)
Injection: 120 mg/1.7 mL (70 mg/mL) solution in a single dose
vial every 4 weeks for 24 weeks
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or female patients of ≥ 18 - 65 years of age.
2. Patients with current/ prior radiographic (X-ray, CT or MRI) evidence of at least one bone metastases from solid tumors.
3. Patients with ECOG score 0 - 2
4. Patients with ability to understand the study procedures and the risks involved, willing to provide written Informed Consent, and able to adhere to study schedules and requirements.
5. Patients with screening laboratory tests within the following criteria:
a. Hemoglobin ≥9.0 g/dL
b. White blood cells ≥3.5 X 109/L
c. Absolute neutrophil count ≥1.5 X 109/L
d. Platelets ≥100 X 109/L
e. Serum transaminase levels ≤2.5 X ULN (≤5 X ULN, in case of liver metastases)
f. Alkaline phosphatase levels ≤5 X ULN
g. Serum creatinine levels ≤150 μmol/L (≤1.7mg/dL)
h. Serum calcium (corrected) levels ≥8 to ≤11.5 mg/dL (2 to 2.9 mmol/L)
6. Women of childbearing potential should neither become pregnant nor lactate and must be using barrier methods of birth control measures during the study period and for 6 months after receiving the last injection of study medication.
ExclusionCriteria
Details
1. Patients with history of hypersensitivity to the denosumab or to drugs with similar chemical structures, or to any of the excipients, or to murine proteins.
2. Previous exposure to denosumab (Prolia, Xgeva, or biosimilar denosumab).
3. Prior intravenous bisphosphonate treatment or current/prior oral bisphosphonates for treatment of bone metastases.
4. Patients who had disorders associated with abnormal bone metabolism including uncontrolled hyperthyroidism or hypothyroidism (except subjects on stable thyroid hormone replacement therapy for last one year), hyperparathyroidism or hypoparathyroidism, Paget’s disease, osteomalacia, osteogenesis imperfecta, cushing’s disease or hyperprolactinemia.
5. Patients with untreated or symptomatic brain metastases.
6. Patients receiving systemic corticosteroids; or received calcitonin, parathyroid hormone related peptides, mithramycin, strontium ranelate, or gallium nitrate within 8 weeks of randomization.
7. Patients requiring radiotherapy or surgery to bone metastases.
8. Patient with severe renal impairment (creatine clearance <30 mL/min) or receiving dialysis.
9. Patients with current or previous osteonecrosis or osteomyelitis of the jaw or non-healed dental/oral surgery or any planned invasive dental procedure during the study.
10. Severe and/or uncontrolled conditions which could compromise participation in the study: Uncontrolled blood pressure (>140/90 mm of Hg); Unstable angina; Congestive heart failure (NYHA grade 3 or more, History of myocardial infarction or stroke within previous 6 months of randomization; Symptomatic arrhythmia requiring medication.
11. Current signs or symptoms of significant, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease that renders the subject incapable of participating in the study.
12. Patients with current or past infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
13. History or presence of any medical or psychiatric condition or disease, or clinically significant laboratory abnormality, physical examination findings or any other condition that, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation and may prevent the subject from completing the study.
14. History of cirrhosis of the liver or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
15. Patients with a history or suspicion of unreliability, poor cooperation or non-compliance with medical treatment.
16. Participation in any clinical study of an investigational product within the previous 3 months.
Method of Generating Random Sequence
Permuted block randomization, variable
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Proportion patients with first on-study Skeletal Related Events (SRE) including hypercalcemia of malignancy associated with bone metastases/lesions.
24 weeks
Secondary Outcome
Outcome
TimePoints
Median time to first on-study Skeletal Related Events (SRE) including hypercalcemia of malignancy associated with bone metastases/lesions.
24 weeks
Time to first and subsequent on-study SREs associated with bone metastases/lesions.
Week 12 and Week 24
Proportion of patients with first and subsequent on-study SREs associated with bone metastases/lesions.
Week 12 and Week 24
Mean number of on-study SREs associated with bone metastases/lesions.
Week 12 and Week 24
Pharmacokinetic parameters comparison of Cmax, AUC0-t, AUC0-28day.
After First Dose Administration
Pharmacodynamic assessment - Percentage change in uNTx/Cr in patients with bone metastases from solid tumors.
From Baseline to Week 4, 8, 12 and 24.
Comparative incidence and titers of anti-Denosumab antibodies.
Week 12 and Week 24
Comparative safety and tolerability for treatment emergent adverse events.
Throughout the study period
Target Sample Size
Total Sample Size="282" Sample Size from India="282" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is a double blind, randomized, active controlled, parallel group clinical study to evaluate the efficacy, safety, and pharmacokinetics of subcutaneous route of administration for the Hetero-Denosumab and Amgen-Denosumab in patients with bone metastases from solid tumorsPatients will be screened for study eligibility based on the inclusion and exclusion criteria. Patients eligible for the study will be randomized to either Hetero-Denosumab or Reference Medicinal Product (Amgen-Denosumab) based on the randomization schedule. All patients shall be administered sub cutaneous injection of 120 mg Denosumab every 4 weeks for 24 weeks. All patients will be followed up for 28 weeks for efficacy and safety assessments. The study is expected to be completed in approximately 18 months after dosing of the first patient.