Risedronate to Prevent Skeletal Related Events in Patients With Metastatic Prostate Cancer Commencing Hormonal Therapy
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|ClinicalTrials.gov Identifier: NCT00216060|
Recruitment Status : Terminated (Terminated due to low accrual)
First Posted : September 22, 2005
Results First Posted : May 26, 2016
Last Update Posted : May 26, 2016
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Prostate Cancer||Drug: Risedronate Drug: Placebo||Phase 3|
OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter, 2 arm study.
The study population will consist of prostate cancer patients with metastatic bone disease for whom androgen-deprivation therapy is planned. After stratification based on the patient's age, performance status, and severity of metastatic disease, the patients will be randomized at a 1:1 ratio to the following treatment arms:
- Daily oral risedronate combined with androgen deprivation
- Daily oral placebo combined with androgen deprivation
Initial clinical evaluation will be performed during the 2-week screening period. While patients receive per-protocol treatment, study assessments will be performed every 4 weeks during the first 3 months, and every 12 weeks thereafter.
Performance Status: Eastern Cooperative Oncology Group (ECOG) 0 to 2
Life Expectancy: At least 12 weeks
- Absolute neutrophil count (ANC) > 1,000/mm3
- Platelet count > 100,000/mm3
- international normalized ratio (INR) < 1.5 x upper limit of normal unless on therapeutic anticoagulation
- Partial thromboplastin time (PTT) < 1.5 x upper limit of normal unless on therapeutic anticoagulation
- Bilirubin < 1.5 mg/dL
- Alanine transaminase (ALT) < 2.5 x upper limit of normal
- Creatinine clearance of > 30 mL/min (by Cockcroft-Gault)
- No significant history of uncontrolled cardiac disease (i.e., uncontrolled hypertension, unstable angina, and congestive heart failure).
- Not specified
- Corrected serum calcium = (4.0 g/dL - actual albumin g/dL)x 0.8 + serum calcium
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||63 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Ability of Risedronate to Prevent Skeletal Related Events in Patients With Metastatic Prostate Cancer Commencing Hormonal Therapy: Hoosier Oncology Group GU02-41|
|Study Start Date :||October 2003|
|Actual Primary Completion Date :||February 2008|
|Actual Study Completion Date :||March 2008|
Experimental: Experimental Arm
Daily oral risedronate combined with androgen deprivation
Daily oral risedronate combined with androgen deprivation
Placebo Comparator: Placebo Arm
daily oral placebo combined with androgen deprivation
Daily oral placebo combined with androgen deprivation
- Numbers of SRE or Death Occurred Cumulatively [ Time Frame: 36 months ]Number of participants experiencing a SRE(skeletal-related event) or death occurred, cumulative from each arm ( a daily oral dose of 30 mg risedronate, or placebo)
- Rate of Patients Archiving a PSA (Prostate Specific Antigen) Nadir < 0.2 ng/mL [ Time Frame: 36 months ]
- Time to Development of Hormone Refractory Disease [ Time Frame: 36 months ]
- Bone Turnover Marker Changes -- Urine Total Deoxypyridinoline (DPD) [ Time Frame: 24 weeks ]
Urine total DPD median in response to treatment on both study arms at week 24. compare median from baseline and week 24.
Deoxypyridinoline (DPD) is measured in hydrolyzed urine samples using high-performance liquid chromatography technique. After extraction of the cross-links and elimination of the urine impurities by a Bio-Rad SPE cartridge (Bio-Rad Laboratories, Hercules, CA), total DPD is eluted from reverse-phase high-performance liquid chromatography by ion pair chromatography with isocratic elution.
The compounds are detected as a result of their natural fluorescence with a fluorescence detector
- Three- Year Survival Rate [ Time Frame: 36 months ]
- Bone Turnover Marker Changes-- Urine N-telopeptide (NTX) Median [ Time Frame: 24 week ]
Urine N-telopeptide (NTX) median changes between baseline and week 24. The assays are performed with the NTx Reagent Pack kit from Ortho-Clinical Diagnostics (Ortho-Clinical Diagnostics/Johnson & Johnson, Amersham, UK), which is a kit designed for the quantitative determination of N-terminal telopeptide (NTx) in human urine on the automated Vitros Immunodiagnostic System ECi (Ortho-Clinical Diagnostics/Johnson & Johnson, Amersham, UK). A competitive immunoassay technique is used. This depends on competition between NTx present in the sample and a synthetic NTx peptide coated on the wells for binding by a horseradish peroxidase (HRP)-labeled antibody conjugate (mouse monoclonal anti-NTx). The conjugate is captured by the peptide coated on the wells; unbound materials are removed by washing.
The bound HRP conjugate is measured by a luminescent reaction.
- Bone Turnover Marker Changes-- Serum BAP [ Time Frame: 24 week ]Serum BAP median changes between baseline and week 24. The Ostase assays are performed with an access immunoassay system, which is an assay of serum samples that provides a quantitative measurement of bone alkaline phosphatase (BAP). A mouse monoclonal antibody specific to BAP is added to a re-action vessel with paramagnetic particles coated with goat antimouse polyclonalantibody.Calibrators,controls,andsamplescontainingBAP are added to the coated particles and bind to the anti-BAP monoclonal antibody. After the formation of a solid phase/capture antibody/BAP complex, separation in a magnetic field and washing remove materials not bound to the solid phase. A chemiluminescent substrate, LumiPhos 530, is added to the reaction vessel, and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of BAP in the sample. The amount of analyte in thesample is determined from a stored multipoint calibration curve
- Bone Turnover Marker Changes-- Serum Osteocalcin (OC) [ Time Frame: 24 week ]Serum Osteocalcin (OC) medians between baseline and 24 weeks areperformed with the Elecsys 2010 automated analyzer, which uses an electrochemiluminescence immunoassay technique for the in vitro quantitative determination of serum total osteocalcin in humanserum. The assay uses a sandwich test principle in which afirst biotinylated monoclonal antibody recognizing N-MID osteocalcin and a second monoclonal antibody against N-MID osteocalcin labeled with ruthenium are incubated with 20mL of serum. After a first incubation, streptavidin-coated microparticles are added for a second incubation, and the complex becomes bound to the solid phase by interaction of biotin and streptavidin.These microparticles are then magnetically captured onto the surface of an electrode. Application of a voltage on this electrode induces chemiluminescent emission, which is measured by a photomultiplierand compared with a calibration curve that is generated in aninstrument-specific manner by 2-point calibration.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00216060
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|Study Chair:||Christopher Sweeney, M.B.B.S.||Hoosier Oncology Group, LLC|