Study To Test The Usage of Denosumab In Patients with Cancer spread to Bone

Phase 3

Recruiting

• Conditions: Secondary malignant neoplasm of bone and bone marrow,

• Registration Number: CTRI/2022/05/042823
• Lead Sponsor: Hetero Biopharma Limited

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-05-30
• Last Update Posted: 2024-02-16

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 282

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Previous exposure to denosumab (Prolia, Xgeva, or biosimilar denosumab).
• Prior intravenous bisphosphonate treatment or current/prior oral bisphosphonates for treatment of bone metastases.
• 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.
• Patients with untreated or symptomatic brain metastases.
• Patients receiving systemic corticosteroids; or received calcitonin, parathyroid hormone related peptides, mithramycin, strontium ranelate, or gallium nitrate within 8 weeks of randomization.
• Patients requiring radiotherapy or surgery to bone metastases.
• Patient with severe renal impairment (creatine clearance <30 mL/min) or receiving dialysis.
• 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.
• 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.
• 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.
• Patients with current or past infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
• 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.
• 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).
• Patients with a history or suspicion of unreliability, poor cooperation or non-compliance with medical treatment.
• Participation in any clinical study of an investigational product within the previous 3 months.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion patients with first on-study Skeletal Related Events (SRE) including hypercalcemia of malignancy associated with bone metastases/lesions.	24 weeks

Secondary Outcome Measures

Name	Time	Method
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
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 safety and tolerability for treatment emergent adverse events.	Throughout the study period
Pharmacokinetic parameters comparison of Cmax, AUC0-t, AUC0-28day.	After First Dose Administration
Median time to first on-study Skeletal Related Events (SRE) including hypercalcemia of malignancy associated with bone metastases/lesions.	24 weeks
Mean number of on-study SREs associated with bone metastases/lesions.	Week 12 and Week 24
Comparative incidence and titers of anti-Denosumab antibodies.	Week 12 and Week 24

Trial Locations

Locations (32)

Bhagwan Mahaveer Cancer Hospital and Research Centre; 🇮🇳 Jaipur, RAJASTHAN, India

All India Institute of Medical Sciences; 🇮🇳 Bhadrak, ORISSA, India

Basavatarakam Indo-American Cancer Hospital and Research Institute; 🇮🇳 Hyderabad, TELANGANA, India

Chittaranjan National Cancer Institute; 🇮🇳 Kolkata, WEST BENGAL, India

Chopda Medicare and Research Centre Pvt. Ltd; Magnum Heart Institute; 🇮🇳 Nashik, MAHARASHTRA, India

Deenanath Mangeshkar Hospital and Research Centre; 🇮🇳 Pune, MAHARASHTRA, India

Dr.B.R.A Institute Rotary Cancer Hospital, All India Institute of Medical Sciences(AIIMS); 🇮🇳 South, DELHI, India

HCG City Cancer Centre; 🇮🇳 Krishna, ANDHRA PRADESH, India

Institute of Post Graduate Medical Education & Research (IPGME&R); 🇮🇳 Kolkata, WEST BENGAL, India

Jubilee Mission Medical College and Research Institute; 🇮🇳 Thrissur, KERALA, India

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Bhagwan Mahaveer Cancer Hospital and Research Centre

🇮🇳Jaipur, RAJASTHAN, India

Dr Naresh Somani

Principal investigator

somanihealthcare@gmail.com