A Study to Compare Denosumab With Zoledronic Acid in Subjects With Bone Metastases From Solid Tumors
Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Fractures, Bone
Intervention: Denosumab 70 mg/mL (Biological); Zoledronic acid 4 mg (Drug); Placebo IV (Drug); Placebo SC (Drug)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: GlaxoSmithKline Official(s) and/or principal investigator(s): GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline
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.
Clinical Details
Official title: DCA114273: A Study Comparing Denosumab With Zoledronic Acid in Subjects of Asian Ancestry With Bone Metastases From Solid Tumors
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: Percent change from Baseline in the bone turnover marker (BTM) uNTx/uCr
Secondary outcome: Percent change from Baseline in bone-specific alkaline phosphatase (s-BALP)Safety and tolerability assessment for adverse events (AEs) Safety and tolerability assessment for Laboratory tests Safety and tolerability assessment for Incidence of anti-denosumab antibodies Pharmacokinetic properties of serum concentrations of denosumab
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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).
Locations and Contacts
GSK Investigational Site, Beijing 100021, China
GSK Investigational Site, Beijing 100034, China
GSK Investigational Site, Beijing 100036, China
GSK Investigational Site, Beijing 100071, China
GSK Investigational Site, Fuzhou 350001, China
GSK Investigational Site, Hangzhou 310016, China
GSK Investigational Site, Harbin, China
GSK Investigational Site, Shanghai 200025, China
GSK Investigational Site, Shanghai 200032, China
GSK Investigational Site, Shanghai 200070, China
GSK Investigational Site, Shanghai 200080, China
GSK Investigational Site, Shanghai 200233, China
GSK Investigational Site, Tianjin 300060, China
GSK Investigational Site, Singapore 119074, Singapore
GSK Investigational Site, Taichung 404, Taiwan
GSK Investigational Site, Taoyuan 333, Taiwan
GSK Investigational Site, Guangzhou, Guangdong 510060, China
GSK Investigational Site, Guangzhou, Guangdong 510120, China
GSK Investigational Site, Guangzhou, Guangdong 510515, China
GSK Investigational Site, Wuhan, Hubei 430030, China
GSK Investigational Site, Nanjing, Jiangsu 210002, China
GSK Investigational Site, Nanjing, Jiangsu 210009, China
GSK Investigational Site, Changchun, Jilin 130012, China
GSK Investigational Site, Chengdu, Sichuan 610041, China
GSK Investigational Site, Hangzhou, Zhejiang 310003, China
Additional Information
Starting date: August 2013
Last updated: July 30, 2015
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