CTRI/2018/06/014501 [Registered on: 11/06/2018] Trial Registered Prospectively
Last Modified On:
24/12/2019
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
To compare and evaluate efficacy and safety of R-TPR-
045 / Xgeva® for prevention of skeletal related events in
patients with bone metastases from solid tumours
Scientific Title of Study
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
Reliance Life Sciences Pvt. Ltd. (RLS), Dhirubhai Ambani Life
Sciences Centre (DALC), R-282, TTC Area of MIDC, Rabale, Navi
Mumbai – 400701, Thane, Maharashtra, India
Reliance Life Sciences Pvt. Ltd. (RLS), Dhirubhai Ambani Life
Sciences Centre (DALC), R-282, TTC Area of MIDC, Rabale, Navi
Mumbai – 400701, Thane, Maharashtra, India
Thane MAHARASHTRA 400701 India
Phone
02235338234
Fax
02235338299
Email
Swapnil.Mirgal@Relbio.com
Source of Monetary or Material Support
Reliance Life sciences Pvt. Ltd. Dhirubhai Ambani Life Sciences Centre Plot R-282, TTC Area of MIDC Thane Belapur Road, Rabale, Navi Mumbai 400 701. India
Primary Sponsor
Name
Reliance Life Sciences Pvt Ltd
Address
Dhirubhai Ambani Life Sciences Centre Plot R-282, TTC Area of MIDC Thane Belapur Road, Rabale, Navi Mumbai 400 701. India
Department of Clinical Oncology, Motkari Nagar, Behind Tupsakahre Lawns, Tidke Colony, Mumbai Naka, Nashik- 422002, Mahrashtra, India Nashik MAHARASHTRA
9766126162
drbtnemade@yahoo.co.in
Dr Viraj Boragaonkar
Seth Nandlal Dhoot Hospital
Department of Oncology, Marathwada Medical Research and Rural Development Institution, A-1, MIDC, Chikalthana, Jalna Road, Aurangabad - 431210, Maharashtra, India Aurangabad MAHARASHTRA
9225330004
viraj.oncosurg@outlook.com
Dr Rajesh Makadia
Shree Giriraj Multi Specialty Hospital
Department of Oncology, 27, Navjyot Park Corner, 150 feet ring road, Rajkot - 360005, Gujarat, India Rajkot GUJARAT
9824255668
makadiarajesh@rocketmail.com
Dr Manjunath Nandennavar
Vyedehi Institute of Medical Science and Research Centre
Department of Medical Oncology, #82, EPIP area, White Field, Bangalore - 560066, Karnataka, India Bangalore KARNATAKA
Recommended dose is 120 mg administered as a single subcutaneous injection
once every 4 weeks into the thigh, abdomen or upper arm till Week 36. All patients should receive the study medication in the upper arm in this study.
Comparator Agent
Xgeva®
Recommended dose is 120 mg administered as a single subcutaneous injection
once every 4 weeks into the thigh, abdomen or upper arm till Week 36. All patients should receive the study medication in the upper arm in this study.
1. Males and females patients of ≥18 -65 years of age.
2. 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.
5. 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.
7. 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.
ExclusionCriteria
Details
1. 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.
6. Patients with severe, untreated hypocalcaemia
7. Patient with rare hereditary problems of fructose intolerance
8. Prior use of Denosumab or ongoing treatment with bisphosphonates.
9. Patients on hormone replacement therapy for menopausal symptoms.
10. 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.
13. 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.).
16. Current smoker or smoking history within 12 months prior to the Screening Visit.
17. 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.
20. Inability to comply with study and/or follow-up procedures.
21. Subjects who are HIV, HBsAg, HCV test positive.
22. 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.
24. Pre-existing central nervous system demyelinating disorders.
25. 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.
26. Participation in any clinical study of an investigational product within the previous 3
months
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Primary - Incidence of first on-study SRE including hypercalcemia of malignancy
associated with bone metastases/lesions in patients with bone metastases from
solid tumours receiving R-TPR-045 / Xgeva®
Co-primary - Median time to first on-study SRE including hypercalcemia of malignancy
associated with bone metastases/lesions in patients with bone metastases from
solid tumours receiving R-TPR-045 / Xgeva®.
Primary - Till Week 24
Co-primary - Median time to first on-study SRE (till Week 36)
Secondary Outcome
Outcome
TimePoints
Time to first and subsequent on-study SREs associated with bone metastases/lesions
Week 12, 24 and 36
Incidence/Proportion of patients with first and subsequent on-study SREs associated
with bone metastases/lesions
week 24 and 36
Mean number of on-study SREs / patient associated with bone metastases/lesions
week 12, 24 and week 36
Assessment of bone repair – change from baseline in nuclear bone scan
week 12,24 and week 36
Quality of life assessment- HRQoL
baseline at week 12,24
and 36
Pharmacodynamic assessment- Percentage change
baseline to week 4,8,12, 24
and 36
Evaluation of safety
across the study
Pharmacokinetic parameters (Cmax, AUC0-t and other PK parameter)
for single dose and multiple dose (at steady state)
Target Sample Size
Total Sample Size="136" Sample Size from India="136" 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)?
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.