To compare and evaluate efficacy and safety of R-TPR-045 / Xgeva® for prevention of skeletal related events inpatients with bone metastases from solid tumours

Phase 3

Active, not recruiting

• Conditions: Patients with bone metastases from solid tumours

• Registration Number: CTRI/2018/06/014501
• Lead Sponsor: Reliance Life Sciences Pvt Ltd

Brief Summary

This is a prospective, multi-center, randomized, double-blind, two-arm, parallel group, active control, comparative clinical study to evaluate efficacy and safety of R-TPR-045 / Xgeva® for prevention of skeletal related events in patients with bone metastases from solid tumours.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-09-28
• Last Update Posted: 2019-12-24

Recruitment & Eligibility

• Status: Closed to Recruitment of Participants
• Sex: All
• Target Recruitment: 136

Inclusion Criteria

• Males and females patients of ≥18 -65 years of age.
• Patients with bone metastases from solid tumours and radiographic evidence of at least one bone metastasis 3.
• Patients with ECOG PS ≤ 2 (after excluding skeletal related morbidity) 4.
• Able to understand the study procedures and the risks involved, willing to provide written Informed Consent, and able to adhere to study schedules and requirements.
• The screening laboratory tests must meet the following criteria: • Haemoglobin ≥9.0 g/dL.
• • WBC ≥3.5 x 109/L • Neutrophils ≥1.5 x 109/L • Platelets ≥100 x 109/L • Serum transaminase ≤2 times the upper limit of normal • Alkaline phosphatase levels ≤2 times the upper limit of normal • Serum creatinine ≤150 μmol/L (≤1.7mg/dL) 6.
• Subjects must have the ability to understand and comply with instructions and be able to complete study-related forms and questionnaires.
• Men and women of childbearing potential must be using adequate birth control measures, as discussed with the study doctor and should agree to continue such precautions for 6 months after receiving the last injection of study medication 8.
• Menopausal females must have experienced their last period more than 12 months prior to study entry to be classified as not of childbearing potential.

Exclusion Criteria

• Patients with multiple myeloma 2.
• Patients who had disorders associated with abnormal bone metabolism including uncontrolled hyper- or hypothyroidism or Paget’s disease; untreated or symptomatic brain metastases 3.
• Patients currently receiving therapy with chronic systemic corticosteroid administration; or received calcitonin, parathyroid hormone related peptides, mithramycin, strontium ranelate, or gallium nitrate within 8 weeks of random assignment 4.
• Patients with life expectancy <6 months 5.
• Patient with severe renal impairment (creatine clearance <30 mL/min) or receiving dialysis.
• Patients with severe, untreated hypocalcaemia 7.
• Patient with rare hereditary problems of fructose intolerance 8.
• Prior use of Denosumab or ongoing treatment with bisphosphonates.
• Hypersensitivity to the active substance or to any of the excipients 11.
• Patient with invasive dental procedures (e.g., tooth extraction, dental implants, oral surgery in last 6months before screening), poor oral hygiene or other pre-existing dental disease 12.
• Current use or known history of systemic (injectable or oral) corticosteroid medication use in last 6 months before screening Visit.
• Patients with planned radiation therapy or surgery to bone 14.
• Patients with current or previous osteonecrosis or osteomyelitis of the jaw, any planned invasive dental procedure during the study 15.
• Significant, non-reversible, active pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, tuberculosis etc.).
• Current smoker or smoking history within 12 months prior to the Screening Visit.
• Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: Uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen; Unstable angina; New York Heart Association (NYHA) greater than/equal to grade 2 congestive heart failure 18.
• Myocardial infarction within 6 months of study enrollment; History of stroke within 6 months of study enrollment; Unstable symptomatic arrhythmia requiring medication (patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible); Clinically significant peripheral vascular disease; Uncontrolled diabetes; Serious active or uncontrolled infection 19.
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
• Inability to comply with study and/or follow-up procedures.
• Subjects who are HIV, HBsAg, HCV test positive.
• 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 23.
• History of serious infection, which caused hospitalization within 6 months prior to randomization or other severe or chronic infection (such as sepsis, abscess or opportunistic infections, invasive fungal infection such as histoplasmosis, or a history of recurrent herpes zoster or other chronic or recurrent infection) or a past diagnosis without sufficient documentation of complete resolution following treatment.
• Pre-existing central nervous system demyelinating disorders.
• 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.
• 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
solid tumours receiving R-TPR-045 / Xgeva®.	Primary - Till Week 24 | Co-primary - Median time to first on-study SRE (till Week 36)
Primary - Incidence of first on-study SRE including hypercalcemia of malignancy	Primary - Till Week 24 | Co-primary - Median time to first on-study SRE (till Week 36)
solid tumours receiving R-TPR-045 / Xgeva®	Primary - Till Week 24 | Co-primary - Median time to first on-study SRE (till Week 36)
Co-primary - Median time to first on-study SRE including hypercalcemia of malignancy	Primary - Till Week 24 | Co-primary - Median time to first on-study SRE (till Week 36)
associated with bone metastases/lesions in patients with bone metastases from	Primary - Till Week 24 | Co-primary - Median time to first on-study SRE (till Week 36)

Secondary Outcome Measures

Name	Time	Method
Quality of life assessment- HRQoL	baseline at week 12,24
Incidence/Proportion of patients with first and subsequent on-study SREs associated	with bone metastases/lesions
Time to first and subsequent on-study SREs associated with bone metastases/lesions	Week 12, 24 and 36
Mean number of on-study SREs / patient associated with bone metastases/lesions	week 12, 24 and week 36
Evaluation of safety	across the study
Assessment of bone repair – change from baseline in nuclear bone scan	week 12,24 and week 36
Pharmacokinetic parameters (Cmax, AUC0-t and other PK parameter)	for single dose and multiple dose (at steady state)
Pharmacodynamic assessment- Percentage change	baseline to week 4,8,12, 24

Trial Locations

Locations (15)

Acharya Tulsi Regional Cancer Treatment and Research Institute (ATRCTRI),; 🇮🇳 Bikaner, RAJASTHAN, India

Aman Hospital and Research Center; 🇮🇳 Vadodara, GUJARAT, India

Bangalore Cancer Centre Pvt Ltd; 🇮🇳 Bangalore, KARNATAKA, India

Government Medical College and Hospital; 🇮🇳 Nagpur, MAHARASHTRA, India

HCG Manavata Cancer Centre; 🇮🇳 Nashik, MAHARASHTRA, India

Indrayani Hospital and Cancer Institute, Shree Narsimha Saraswati Medical Foundation; 🇮🇳 Pune, MAHARASHTRA, India

IPGME&R SSKM Hospital; 🇮🇳 Kolkata, WEST BENGAL, India

K R Hospital, Mysore Medical College and Research Institute; 🇮🇳 Mysore, KARNATAKA, India

KLES Dr. Prabhakar Kore Hospital and Medical Research Centre; 🇮🇳 Belgaum, KARNATAKA, India

Maulana Azad Medical College and Associated Lok Nayak Hospital; 🇮🇳 Delhi, DELHI, India

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Acharya Tulsi Regional Cancer Treatment and Research Institute (ATRCTRI),

🇮🇳Bikaner, RAJASTHAN, India

Dr Surender Kumar Beniwal

Principal investigator

9414370484

beniwal.surendra@gmail.com