Risedronate to Prevent Skeletal Related Events in Patients With Metastatic Prostate Cancer Commencing Hormonal Therapy

Metastatic Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00216060
• Other study ID #: HOG GU02-41
• Status: Terminated
• Phase: Phase 3
• First received: September 13, 2005
• Last updated: May 25, 2016
• Start date: October 2003
• Est. completion date: March 2008

Study information

• Verified date: May 2016
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Risedronate is an orally administered pyridinyl bisphosphonate that is 36 times more potent than pamidronate and 72 times more potent than clodronate. Four randomized, double-blind trials have been carried out in patients with postmenopausal osteoporosis. In 2 of these studies, vertebral fracture incidence was reduced by a daily dose of 5 mg risedronate by up to 65% and 49% relative to placebo after 1 and 3 years, respectively. In these trials, risedronate improved lumbar spine, femoral neck, and femoral trochanter bone mineral density (BMD) at 6 months. In addition, preclinical studies have shown that risedronate is more potent than pamidronate and clodronate in inhibiting adhesion of prostate cancer cells to bone and preventing tumor cell invasion. The incidence of osteoporosis in prostate cancer patients has been well established; therefore, it is advantageous to assess the efficacy of oral bisphosphonate therapy.

Description:

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

Hematopoietic:

• 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

Hepatic:

• Bilirubin < 1.5 mg/dL

• Alanine transaminase (ALT) < 2.5 x upper limit of normal

Renal:

• Creatinine clearance of > 30 mL/min (by Cockcroft-Gault)

Cardiovascular:

• No significant history of uncontrolled cardiac disease (i.e., uncontrolled hypertension, unstable angina, and congestive heart failure).

Pulmonary:

• Not specified

Calcium:

• Corrected serum calcium = (4.0 g/dL - actual albumin g/dL)x 0.8 + serum calcium

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 63
• Est. completion date: March 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate with metastatic bone disease (by CT, MRI or bone scan) with plans to start or be < 30 days from beginning androgen deprivation therapy. Patients with lymph node or visceral metastases only are not eligible

• Patients may receive palliative radiation therapy at the investigators discretion during the first 4 weeks of beginning protocol therapy.

Exclusion Criteria:

• No neuroendocrine, small cell or transitional cell cancer of the prostate No abnormal bone metabolism (i.e., Paget's disease, untreated hyperthyroidism, untreated hyperprolactinemia, untreated Cushing's disease).

• No use of calcitonin within 14 days before being registered for protocol therapy or any previous use of bisphosphonates.

• No major surgery within 4 weeks of registration to protocol therapy.

• No adjuvant chemotherapy within 6 months of registration to protocol therapy.

• No previous chemotherapy for metastatic disease.

• No hormonal therapy in the adjuvant setting within 12 months of registration to protocol therapy; previous hormonal therapy must not have exceeded 6 months.

• No prior history of malignancy in the past 5 years with the exception of basal cell and squamous cell carcinoma of the skin.

• No history of allergy or drug reactions to bisphosphonates.

Study Design

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

Related Conditions & MeSH terms

• Metastatic Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Risedronate
Daily oral risedronate combined with androgen deprivation
• Placebo
Daily oral placebo combined with androgen deprivation

Locations

Country	Name	City	State
Canada	Male/Female Health and Research	Barrie	Ontario
Canada	Burlington Professional Centre	Burlington	Ontario
Canada	Urology Resource Centre	Burlington	Ontario
Canada	Dr. Allan Patrick Professional Corporation	Fredericton	New Brunswick
Canada	Hamilton District Urology Research Center	Hamilton	Ontario
Canada	Southern Interior Medical Research, Inc.	Kelowna	British Columbia
Canada	Centre for Advanced Urological Research	Kingston	Ontario
Canada	London Region Cancer Program	London	Ontario
Canada	MOR Urology, Inc.	New Market	Ontario
Canada	Male Health Centres	Oakville	Ontario
Canada	Scarborough General Hospital, Medical Mall	Scarborough	Ontario
Canada	Andreou Research	Surrey	British Columbia
Canada	University Health Network - Princess Margaret Division	Toronto	Ontario
Canada	Dr. G. Steinhoff Clinical Research	Victoria	British Columbia
United States	Urologic Surgery Associates	Baltimore	Maryland
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Oncology Hematology Associates of SW Indiana	Evansville	Indiana
United States	Medical & Surgical Specialists, LLC	Galesburg	Illinois
United States	Accumed Research Associates	Garden City	New York
United States	Center for Cancer Care at Goshen Health System	Goshen	Indiana
United States	Drs. Werner, Murdock and Francis PA Urology Associates	Greenbelt	Maryland
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Quality Cancer Center (MCGOP)	Indianapolis	Indiana
United States	Urology of Indiana, LLC	Indianapolis	Indiana
United States	Kansas City Urology Care	Kansas City	Missouri
United States	Center for Urological Research	La Mesa	California
United States	Gundersen Lutheran Medical Center	LaCrosse	Wisconsin
United States	Urological Associates of Lancaster	Lancaster	Pennsylvania
United States	Urology Associates	Muncie	Indiana
United States	Grove Hill Medical Center Urology	New Britain	Connecticut
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Peoria Urological Associates	Peoria	Illinois
United States	Triangle Urological Group	Pittsburgh	Pennsylvania
United States	Nevada Urology	Reno	Nevada
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Salt Lake Research	Salt Lake City	Utah
United States	San Bernadino Urological Associates	San Bernardino	California
United States	David Reed, M.D.	Seattle	Washington
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Oregon Urology Specialists	Springfield	Oregon
United States	Siteman Cancer Center	St. Louis	Missouri
United States	Staten Island Urological Research, P.C.	Staten Island	New York
United States	Madigan Army Medical Center Urology Service	Tacoma	Washington
United States	Innovative Surgical Resources	Tampa	Florida
United States	Lawrenceville Urology	Trenton	New Jersey

Sponsors (4)

Lead Sponsor	Collaborator
Christopher Sweeney, MBBS	Hoosier Cancer Research Network, Sanofi, Walther Cancer Institute

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

C. Sweeney, W. M. Dugan II, R. Dreicer, F. Chu, G. Parks, K. Baker, D. Reed, K. Jansz, J. Zadra, C. T. Yiannoutsos. J Clin Oncol 28, 2010 (suppl; abstr e15000)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numbers of SRE or Death Occurred Cumulatively	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)	36 months	No
Secondary	Rate of Patients Archiving a PSA (Prostate Specific Antigen) Nadir < 0.2 ng/mL		36 months	No
Secondary	Time to Development of Hormone Refractory Disease		36 months	No
Secondary	Bone Turnover Marker Changes -- Urine Total Deoxypyridinoline (DPD)	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	24 weeks	No
Secondary	Three- Year Survival Rate		36 months	No
Secondary	Bone Turnover Marker Changes-- Urine N-telopeptide (NTX) Median	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.	24 week	No
Secondary	Bone Turnover Marker Changes-- Serum BAP	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	24 week	No
Secondary	Bone Turnover Marker Changes-- Serum Osteocalcin (OC)	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.	24 week	No