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

NCT ID: NCT00216060

Last Updated: 2016-05-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-10-31
• Study Completion Date: 2008-03-31

Brief 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.

Detailed 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

Conditions

Metastatic Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Experimental Arm

Daily oral risedronate combined with androgen deprivation

Group Type: EXPERIMENTAL

Risedronate

Intervention Type: DRUG

Daily oral risedronate combined with androgen deprivation

Placebo Arm

daily oral placebo combined with androgen deprivation

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Daily oral placebo combined with androgen deprivation

Interventions

Risedronate

Daily oral risedronate combined with androgen deprivation

Intervention Type: DRUG

Placebo

Daily oral placebo combined with androgen deprivation

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Walther Cancer Institute

OTHER

Sponsor Role: collaborator

Hoosier Cancer Research Network

OTHER

Sponsor Role: collaborator

Christopher Sweeney, MBBS

OTHER

Sponsor Role: lead

Responsible Party

Christopher Sweeney, MBBS

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Christopher Sweeney, M.B.B.S.

Role: STUDY_CHAIR

Hoosier Oncology Group, LLC

Locations

Center for Urological Research

La Mesa, California, United States

San Bernadino Urological Associates

San Bernardino, California, United States

Grove Hill Medical Center Urology

New Britain, Connecticut, United States

Innovative Surgical Resources

Tampa, Florida, United States

Medical & Surgical Specialists, LLC

Galesburg, Illinois, United States

Peoria Urological Associates

Peoria, Illinois, United States

Oncology Hematology Associates of SW Indiana

Evansville, Indiana, United States

Center for Cancer Care at Goshen Health System

Goshen, Indiana, 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

Urology Associates

Muncie, Indiana, United States

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Urologic Surgery Associates

Baltimore, Maryland, United States

Drs. Werner, Murdock and Francis PA Urology Associates

Greenbelt, Maryland, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Kansas City Urology Care

Kansas City, Missouri, United States

Siteman Cancer Center

St Louis, Missouri, United States

Nevada Urology

Reno, Nevada, United States

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Lawrenceville Urology

Trenton, New Jersey, United States

Accumed Research Associates

Garden City, New York, United States

Staten Island Urological Research, P.C.

Staten Island, New York, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Oregon Urology Specialists

Springfield, Oregon, United States

Urological Associates of Lancaster

Lancaster, Pennsylvania, United States

Triangle Urological Group

Pittsburgh, Pennsylvania, United States

Salt Lake Research

Salt Lake City, Utah, United States

David Reed, M.D.

Seattle, Washington, United States

Madigan Army Medical Center Urology Service

Tacoma, Washington, United States

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States

Southern Interior Medical Research, Inc.

Kelowna, British Columbia, Canada

Andreou Research

Surrey, British Columbia, Canada

Dr. G. Steinhoff Clinical Research

Victoria, British Columbia, Canada

Dr. Allan Patrick Professional Corporation

Fredericton, New Brunswick, Canada

Male/Female Health and Research

Barrie, Ontario, Canada

Burlington Professional Centre

Burlington, Ontario, Canada

Urology Resource Centre

Burlington, Ontario, Canada

Hamilton District Urology Research Center

Hamilton, Ontario, Canada

Centre for Advanced Urological Research

Kingston, Ontario, Canada

London Region Cancer Program

London, Ontario, Canada

MOR Urology, Inc.

Newmarket, Ontario, Canada

Male Health Centres

Oakville, Ontario, Canada

Scarborough General Hospital, Medical Mall

Scarborough Village, Ontario, Canada

University Health Network - Princess Margaret Division

Toronto, Ontario, Canada

Countries

United States; Canada

References

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)

Reference Type: RESULT

Jakob T, Tesfamariam YM, Macherey S, Kuhr K, Adams A, Monsef I, Heidenreich A, Skoetz N. Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone metastases: a network meta-analysis. Cochrane Database Syst Rev. 2020 Dec 3;12(12):CD013020. doi: 10.1002/14651858.CD013020.pub2.

Reference Type: DERIVED

PMID: 33270906 (View on PubMed)

Hahn NM, Yiannoutsos CT, Kirkpatrick K, Sharma J, Sweeney CJ. Failure to suppress markers of bone turnover on first-line hormone therapy for metastatic prostate cancer is associated with shorter time to skeletal-related event. Clin Genitourin Cancer. 2014 Feb;12(1):33-40.e4. doi: 10.1016/j.clgc.2013.07.002. Epub 2013 Oct 12.

Reference Type: DERIVED

PMID: 24126237 (View on PubMed)

Other Identifiers

HOG GU02-41

Identifier Type: -

Identifier Source: org_study_id