| CTRI Number |
CTRI/2023/09/057660 [Registered on: 14/09/2023] Trial Registered Prospectively |
| Last Modified On: |
20/03/2026 |
| 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 Study of the Long-term Use of Hetero Denosumab in Patients of Bone Cancer |
|
Scientific Title of Study
|
A Phase IIIb, Prospective, Multicenter, Parallel, Assessor Blinded Extension Study to Evaluate the long-term Efficacy, Immunogenicity, Safety of Subcutaneous Injection of Denosumab (Hetero) in patients with bone metastases from solid tumours |
| Trial Acronym |
Nil |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| HCR/IIIb/DENOSOLEXT/01/2023 Version 1.0 Dated 08-Mar-2023 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
|
| Name |
Dr Sreenivasa Chary S |
| Designation |
Senior General Manager |
| Affiliation |
Hetero Labs Limited |
| Address |
7-2-A2, Industrial Estates, Sanath Nagar
Hyderabad
TELANGANA
500018
India |
| Phone |
914023704923 |
| Fax |
91-40-23801902 |
| Email |
Sreenivasa.Chary@hetero.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Subhadeep Sinha |
| Designation |
Senior Vice President |
| Affiliation |
Hetero Drugs Limited |
| Address |
7-2-A2, Industrial Estates, Sanath Nagar
Hyderabad
TELANGANA
500018
India |
| Phone |
914023704923 |
| Fax |
91-40-23801902 |
| Email |
sd.sinha@hetero.com |
|
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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. & 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. & Fax No.: 914023810110 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
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Details of Secondary Sponsor
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Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 10 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Sandeep Vithoba Ishi |
Chopda Medicare |
Magnum Heart Institute, 3/5, Patil Lane No.1, Laxmi Nagar, Near K.B.H Vidyalaya, Canada Corner, Nashik – 422005, Maharashtra, India
Nashik
MAHARASHTRA |
8655321807
dr.sandeepishi@gmail.com |
| Dr Lakhsmi Priyadarshini |
HCG Cancer Centre |
33-22-33, Ch Venkata krishnayya street, Suryarao pet, Vijayawada 520002
Krishna
ANDHRA PRADESH |
9966030988
priyadarshini006@gmail.com |
| Dr Rajesh Kumar Singh |
Indhira Gandhi Institute of Medical Sciences |
Department of Medical Oncology, Sheikpura, Patna - 800014
Sheikhpura
BIHAR |
9939088899
drrajeshrccigimstrial@gmail.com |
| Dr Koushik Chatterjee |
Institution of Post Graduate Medical Education & Research |
Department of Medical Oncology, 244, AJC, Bose Road - 700020
Kolkata
WEST BENGAL |
9874357580
drkoushik.chatterjee@gmail.com |
| Dr Abhinav Bhagwan Zawar |
Kamalnayan Bajaj Hospital |
Department of Medical Oncology, Gut No.43, Satara Parisar, Beed Bypass Road, Aurangabad-431010
Aurangabad
MAHARASHTRA |
9901835738
abhinav.zawar@gmail.com |
| DrPRadhika |
MNJ Hospital |
Department of Medical Oncology, Red Hills, Hyderabad – 500004
Hyderabad
TELANGANA |
9848792682
radhika.parimkayala@gmail.com |
| Dr Ravindra Singh Gothwal |
SMS Hospital, Department of Radiation Oncology |
Department of Medical Oncology, Room No. 46, Fourth Floor, Dhanvantri OPD Block, Jaipur-302004
Jaipur
RAJASTHAN |
9887038220
drravindragothwal@yahoo.com |
| Dr Ghanashyam Biswas |
Sparsh Hospitals & Critical Care Private Limited |
Plot No – A/407, Saheed Nagar, Bhubaneswar-751007, Odisha, India.
Khordha
ORISSA |
9937500878
drgbiswas@gmail.com |
| DrV M Durai Mavalavan |
SRM Medical College |
Department of Medical Oncology, Kattankulathur- 603203
Kancheepuram
TAMIL NADU |
9941702373
dmavalavan@yahoo.co.in |
| Dr Kaushal Kalra |
Vardhman Mahavir Medical College & Safdarjung Hospital |
Department of Medical Oncology, New-Delhi - 110029
New Delhi
DELHI |
9968663394
kaushalkalra@yahoo.com |
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Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 10 |
| Name of Committee |
Approval Status |
| Ethics Committee Kamalnayan Bajaj Hospital |
Submittted/Under Review |
| Ethics Committee S.M.S. Medical College and Attached Hospitals |
Submittted/Under Review |
| HCG Curie City Cancer Centre |
Approved |
| Institutional Ethics Committee MNJ Institute of Oncology & Regional Cancer |
Submittted/Under Review |
| Institutional Ethics Committee Sparsh Hospital, Sparsh Hospitals & Critical Care (P) Ltd |
Approved |
| Institutional Ethics Committee SRM Medical College Hospital |
Submittted/Under Review |
| Institutional Ethics Committee VMMC and SJH VMMC and Safdarjung Hospital |
Submittted/Under Review |
| Institutional Ethics Committee, IGIMS |
Submittted/Under Review |
| IPGME & R Research Oversight Committee, Office of the Dean, Institute of Post Graduate Medical Education & Research |
Submittted/Under Review |
| Magna Care Ethics Committee |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C795||Secondary malignant neoplasm of bone and bone marrow, |
|
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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 (Amgen) |
Injection: 120 mg/1.7 mL (70 mg/mL) solution in a single dose vial every 4 weeks for 24 weeks |
|
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Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1.Patients who have completed the 24 weeks of study HCR/III/DENOSOL/12/2019.
2.Patients with ECOG score 0 - 2
3.Patients willing to provide written Informed Consent for extension study, and able to adhere to study schedules and requirements.
4.Patients with screening laboratory tests within the following criteria:
a.Haemoglobin ≥9.0 g/dL
b.WBC ≥3.5 X 109/L
c.Absolute Neutrophil Count ≥1.5 X 109/L
d.Platelets ≥100 X 109/L
e.Serum transaminase levels ≤2.5xULN (≤5xULN, in case of liver metastases)
f.Alkaline phosphatase levels ≤5xULN
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)
5.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
|
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| ExclusionCriteria |
| Details |
1.Patients with untreated or symptomatic brain metastases.
2.Patient with severe renal impairment (creatinine clearance <30 mL/min) or receiving dialysis.
3.Patients with severe hypocalcaemia (corrected serum calcium of < 8.0 mg/dL or <2 mmol/L).
4.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.
5.Current signs or symptoms of significant, progressive or uncontrolled renal, hepatobiliary, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, vascular, neurologic or cerebral, psychiatric disease that renders the subject incapable of participating in the study.
6.Patients with disorders associated with abnormal bone metabolism including uncontrolled hyperthyroidism or hypothyroidism, hyperparathyroidism or hypoparathyroidism, Paget’s disease, osteomalacia, osteogenesis imperfecta, Cushing’s disease or hyperprolactinemia.
7.Patients requiring radiotherapy or surgery to bone metastases; or those currently receiving oral bisphosphonates; or have previously received IV bisphosphonate therapy for treatment of bone metastases.
8.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.
9.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.
10. 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)
11.Patient who has discontinued/withdrawn from the study HCR/III/DENOSOL/12/2019.
12.Patient who has tested positive for anti-denosumab antibodies in previous study HCR/III/DENOSOL/12/2019.
13.Patient who has not benefited from denosumab therapy in study HCR/III/DENOSOL/12/2019 as per Investigator’s discretion.
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Method of Generating Random Sequence
|
Permuted block randomization, variable |
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Method of Concealment
|
Centralized |
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Blinding/Masking
|
Outcome Assessor Blinded |
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Primary Outcome
|
| Outcome |
TimePoints |
Median time to first on-study Skeletal Related Events (SRE) including hypercalcemia of malignancy associated with bone metastases/lesions during 12 months.
Proportion of patients with first on-study Skeletal Related Events (SRE) including hypercalcemia of malignancy associated with bone metastases/lesions for 12 months.
|
12 Months |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Median time to first & subsequent on-study SREs associated with bone metastases/lesions. |
12 months |
| Proportion of patients with first & subsequent on-study SREs associated with bone metastases/lesions. |
12 months |
| Mean number of on-study SREs associated with bone metastases/lesions. |
12 months |
Comparative incidence & titers of anti-denosumab antibodies.
|
12 months |
| Comparative safety & tolerability for treatment emergent adverse events by monitoring of significant clinical signs & symptoms & laboratory abnormalities during treatment. |
12 months |
|
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Target Sample Size
|
Total Sample Size="60"
Sample Size from India="60"
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)
|
20/09/2023 |
| 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="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
N/A |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
|
· This study is an extension study of HCR/III/DENOSOL/12/2019 to evaluate the long-term efficacy, immunogenicity and safety of subcutaneous Hetero-denosumab and Reference medicinal product (Denosumab, Amgen) in patients with bone metastases from solid tumours, who have completed 24 weeks (06 months) treatment on the HCR/III/DENOSOL/12/2019 study. · This study will be an assessor blinded, active controlled, comparative, parallel group study. |