A Study to Compare Denosumab With Zoledronic Acid in Subjects With Bone Metastases From Solid Tumors

Fractures, Bone Clinical Trial

Official title:

DCA114273: A Study Comparing Denosumab With Zoledronic Acid in Subjects of Asian Ancestry With Bone Metastases From Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01920568
• Other study ID #: 114273
• Status: Active, not recruiting
• Phase: Phase 3
• First received: August 8, 2013
• Last updated: March 24, 2016
• Start date: August 2013
• Est. completion date: May 2016

Study information

• Verified date: March 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, double-dummy study designed to provide bridging data in an Asian population to Amgen's studies of denosumab in subjects with bone metastases from solid tumors. The study is designed to provide data to a large global dataset of phase-III studies including breast cancer, prostate cancer, and all solid tumors, plus multiple myeloma, to support the regulatory approval for marketing and patient access to denosumab for the prevention of SREs in Chinese subjects with bone metastases from solid tumors. The primary objective of this study is to evaluate and compare the percent change from baseline to Week 13 in the bone marker urinary amino-terminal cross-linking telopeptide of type I collagen (uNTx) corrected for urine creatinine (uNTx/uCr) in subjects treated with denosumab to those treated with zoledronic acid. The study is designed to test the superiority of denosumab over zoledronic acid.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 487
• Est. completion date: May 2016
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subject understands the nature and purpose of this study and the study procedures, which have been explained by the Investigator or delegate, and subject has signed the written informed consent for the overall study. The subject must sign a separate written informed consent to be eligible for enrolment in the pharmacokinetic substudy.

• Adult (aged >=18 years) of Asian ancestry with a histologically or cytologically confirmed solid tumor. In addition, subjects who are enrolled at a center in mainland China or at an SFDA-certified center in Hong Kong including the approximately 33 subjects in the pharmacokinetic substudy must be of Chinese race, ancestry, or heritage. Subjects enrolled in other regions or countries, such as Taiwan and Singapore, or at a non-SFDA-certified center in Hong Kong, are not required to be of Chinese race or ancestry.

• Current or prior documented radiographic evidence (i.e., x-ray, computer tomography [CT], or magnetic resonance imaging [MRI]) of at least 1 bone metastasis.

• Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, as defined below, during the study and for 6 months after end of study treatment. Women who report having a pregnancy during this study will be followed for birth outcomes. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows: An intrauterine device or intrauterine system with a documented failure rate of less than 1% per year; Male partner sterilization prior to the female subject's enrollment and the male is the sole sexual partner for that subject; the information on the male sterility can come from the site personnel's review of subject's medical records; medical examination of the subject and/or semen analysis; or interview with the subject on his medical history; complete abstinence from sexual intercourse for 14 days prior to first dose of study treatment, through the dosing period, and for at least 7 months after the last dose of study treatment; double-barrier contraception: male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository); implants of levonorgestrel or etonogestrel where not contraindicated for this patient population or per local practice; injectable progesterone where not contraindicated for this patient population or per local practice; percutaneous contraceptive patches where not contraindicated for this patient population or per local practice; Oral contraceptives (either combined or progesterone only) where not contraindicated for this patient population or per local practice. Females of child bearing potential who do not have male partners as part of their preferred and usual lifestyle are not required to use contraception.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (refer protocol for details).

• Adequate baseline organ function as defined by the following criteria: Serum aspartate aminotransferase (AST) <=2.0 x upper limit of normal (ULN); Serum alanine aminotransferase (ALT) <=2.0 x ULN; Serum total bilirubin <=1.0 x ULN; creatinine clearance (calculated using the Cockcroft-Gault formula) >=30 milliliter per minute (mL/min); serum calcium or albumin-adjusted serum calcium >=2.0 millimole per liter (mmol/L) (8.0 mg/dL) and <=2.9 mmol/L (11.5 miligram per deciliter [mg/dL]). Subjects must not have taken supplemental calcium for at least 8 hours prior to collection of the blood sample for screening serum calcium determination.

• Life expectancy of at least 6 months, in the opinion of the Investigator.

Exclusion Criteria:

• Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that, in the opinion of the Investigator, could interfere with subject's safety, obtaining informed consent or compliance to the study procedures; The Investigator should consult the GSK Medical Monitor prior to enrolling a subject if s/he is unsure if a condition might interfere with the subject's safety or participation in this study.

• Any prior treatment with intravenous (IV) or oral bisphosphonates.

• Prior treatment with denosumab.

• Planned radiation therapy or surgery to bone.

• Known brain metastases.

• Prior history or current evidence of osteomyelitis or osteonecrosis of the jaws (ONJ), an active dental or jaw condition that requires oral surgery, non-healed dental or oral surgery, or planned invasive dental procedure over the course of the study.

• Evidence of any of the following conditions per subject self report or medical chart review: any prior or current malignancy (other than the cancer under study in this protocol) with active disease within 3 years before randomization; 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); known infection with human immunodeficiency virus (HIV); active infection with hepatitis B or hepatitis C virus.

• Pregnant women, women planning to become pregnant within 7 months after end of study treatment, and women who are breastfeeding. Women who are breast feeding should discontinue nursing prior to the first dose of study treatment and should refrain from nursing throughout the treatment period and for 7 months following their last dose of study treatment.

• Male subjects unable or unwilling to use adequate contraception methods during the study and for 6 months after end of study treatment should be excluded.

• Subject is currently enrolled in another investigational device or investigational product study, or has not completed at least 30 days, 5 half lives, or the duration of biological effect, whichever is longer, since ending such a study.

• Known sensitivity to any of the investigational products or supplements to be administered during the study (i.e., zoledronic acid, mammalian derived products, calcium, or vitamin D).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fractures, Bone

Intervention

Biological:
• Denosumab 70 mg/mL
Denosumab will be given as a SC injection of 120 mg by administering a 1.7 mL volume in a single injection

Drug:
• Zoledronic acid 4 mg
Zoledronic acid 4 mg (or equivalent clearance-adjusted dose in subjects with baseline creatinine clearance <=60 ml/min) will be diluted in either 0.9% sodium chloride or 5% dextrose injection and administered IV.
• Placebo IV
The placebo will consist of 1.7 mL 0.9% w/v sodium chloride
• Placebo SC
The placebo will consist of either 0.9% w/v sodium chloride or 5% dextrose injection

Locations

Country	Name	City	State
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Changchun	Jilin
China	GSK Investigational Site	Chengdu	Sichuan
China	GSK Investigational Site	Fuzhou
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Hangzhou	Zhejiang
China	GSK Investigational Site	Hangzhou
China	GSK Investigational Site	Harbin
China	GSK Investigational Site	Nanjing	Jiangsu
China	GSK Investigational Site	Nanjing	Jiangsu
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Tianjin
China	GSK Investigational Site	Wuhan	Hubei
Singapore	GSK Investigational Site	Singapore
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taoyuan

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	Amgen

Countries where clinical trial is conducted

China,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change from Baseline in the bone turnover marker (BTM) uNTx/uCr	Urine samples will be collected prior to administration of study treatment for the assessment of urine creatinine (uCr) and urine NTx (uNTx).	From Baseline up to Week 13	No
Secondary	Percent change from Baseline in bone-specific alkaline phosphatase (s-BALP)	Blood samples will be obtained for the assessment of s-BALP	From Baseline up to Week 13	No
Secondary	Safety and tolerability assessment for adverse events (AEs)		From Baseline up to Week 73/Early Withdrawal	No
Secondary	Safety and tolerability assessment for Laboratory tests	Blood sample will be collected for Laboratory tests includes serum chemistry and hematology	From Baseline up to Week 53	No
Secondary	Safety and tolerability assessment for Incidence of anti-denosumab antibodies	Blood sample will be collected for the testing for anti-denosumab antibodies	From Day 1 up to Week 53/Early Withdrawal	No
Secondary	Pharmacokinetic properties of serum concentrations of denosumab		Predose sample on Day 1, Week 5, 9, 13, 17, 19 (no dose), 21, 25 and Week 49	No