Clinical trial NCT00216060: Risedronate to Prevent Skeletal Related Events in Patients With Metastatic Prostate Cancer Commencing Hormonal Therapy
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Metastatic Prostate Cancer
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Sanofi
name: Walther Cancer Institute
name: Hoosier Cancer Research Network
First posted: 2005-09-22
Enrollment: 63
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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.

Primary outcomes:
measure: Numbers of SRE or Death Occurred Cumulatively
timeFrame: 36 months
Secondary outcomes:
measure: Rate of Patients Archiving a PSA (Prostate Specific Antigen) Nadir < 0.2 ng/mL
timeFrame: 36 months
measure: Time to Development of Hormone Refractory Disease
timeFrame: 36 months
measure: Bone Turnover Marker Changes -- Urine Total Deoxypyridinoline (DPD)
timeFrame: 24 weeks
measure: Three- Year Survival Rate
timeFrame: 36 months
measure: Bone Turnover Marker Changes-- Urine N-telopeptide (NTX) Median
timeFrame: 24 week
measure: Bone Turnover Marker Changes-- Serum BAP
timeFrame: 24 week
measure: Bone Turnover Marker Changes-- Serum Osteocalcin (OC)
timeFrame: 24 week
Other outcomes:
Locations:
city: La Mesa
country: United States
facility: Center for Urological Research
state: California
city: San Bernardino
country: United States
facility: San Bernadino Urological Associates
state: California
city: New Britain
country: United States
facility: Grove Hill Medical Center Urology
state: Connecticut
city: Tampa
country: United States
facility: Innovative Surgical Resources
state: Florida
city: Galesburg
country: United States
facility: Medical & Surgical Specialists, LLC
state: Illinois
city: Peoria
country: United States
facility: Peoria Urological Associates
state: Illinois
city: Evansville
country: United States
facility: Oncology Hematology Associates of SW Indiana
state: Indiana
city: Goshen
country: United States
facility: Center for Cancer Care at Goshen Health System
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Quality Cancer Center (MCGOP)
state: Indiana
city: Indianapolis
country: United States
facility: Urology of Indiana, LLC
state: Indiana
city: Muncie
country: United States
facility: Urology Associates
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Baltimore
country: United States
facility: Urologic Surgery Associates
state: Maryland
city: Greenbelt
country: United States
facility: Drs. Werner, Murdock and Francis PA Urology Associates
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City Urology Care
state: Missouri
city: St. Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Reno
country: United States
facility: Nevada Urology
state: Nevada
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Trenton
country: United States
facility: Lawrenceville Urology
state: New Jersey
city: Garden City
country: United States
facility: Accumed Research Associates
state: New York
city: Staten Island
country: United States
facility: Staten Island Urological Research, P.C.
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Springfield
country: United States
facility: Oregon Urology Specialists
state: Oregon
city: Lancaster
country: United States
facility: Urological Associates of Lancaster
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Triangle Urological Group
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Salt Lake Research
state: Utah
city: Seattle
country: United States
facility: David Reed, M.D.
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center Urology Service
state: Washington
city: LaCrosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
city: Kelowna
country: Canada
facility: Southern Interior Medical Research, Inc.
state: British Columbia
city: Surrey
country: Canada
facility: Andreou Research
state: British Columbia
city: Victoria
country: Canada
facility: Dr. G. Steinhoff Clinical Research
state: British Columbia
city: Fredericton
country: Canada
facility: Dr. Allan Patrick Professional Corporation
state: New Brunswick
city: Barrie
country: Canada
facility: Male/Female Health and Research
state: Ontario
city: Burlington
country: Canada
facility: Burlington Professional Centre
state: Ontario
city: Burlington
country: Canada
facility: Urology Resource Centre
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton District Urology Research Center
state: Ontario
city: Kingston
country: Canada
facility: Centre for Advanced Urological Research
state: Ontario
city: London
country: Canada
facility: London Region Cancer Program
state: Ontario
city: New Market
country: Canada
facility: MOR Urology, Inc.
state: Ontario
city: Oakville
country: Canada
facility: Male Health Centres
state: Ontario
city: Scarborough
country: Canada
facility: Scarborough General Hospital, Medical Mall
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Princess Margaret Division
state: Ontario
Study officials:
affiliation: Hoosier Oncology Group, LLC
name: Christopher Sweeney, M.B.B.S.
role: STUDY_CHAIR
References:
citation: 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)
citation: 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.
citation: 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.