Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer

It is the aim of this prospective, single-group, clinical study to assess whether bone parameters can be used as diagnostic tools for early detection of bone metastases in patients with high risk prostate cancer. The usefulness in monitoring zoledronic acid therapy in patients who have developed bone metastases will also be assessed.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Zoledronic acid

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Tuebingen, Germany
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion criteria:

• Patients with histologically confirmed diagnosis of prostate cancer who have not yet developed bone metastases
• Prostate cancer patients with a rise in PSA under hormone therapy.

PSA criteria:

• Patients who have undergone prostatectomy: any rise in PSA or
• Patients without prostatectomy: 2 consecutive rises in PSA levels relative to a previous reference value, separated by one month. The first measurement must occur one month after the reference value and must be above the reference value. The second confirmatory measurement taken one month after the first measurement must be greater than the first measurement.
• Previous chemotherapy or radiotherapy must have been performed ≥ 8 weeks prior to study entry.
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 (patients that spend less than 50% of time in bed during the day)
• Adequate liver function - serum total bilirubin concentration less than 1.5 x upper limit of normal value
• Age: ≥ 18 years
• Patient has given written informed consent prior to any study-specific procedures. Patients with psychiatric or addictive disorders which prevent them from giving their informed consent must not enter the study.

Exclusion criteria:

• Prior treatment with a bisphosphonate
• Abnormal renal function as evidenced by a calculated creatinine clearance < 30 ml/minute.
• Corrected (adjusted for serum albumin) serum calcium concentration < 8.0 mg/dl (2.00 mmol/L) or ≥ 12.0 mg/dl (3.00 mmol/L).
• Patients with clinically symptomatic brain metastases
• History of diseases with influence on bone metabolism such as Paget's disease and primary hyperparathyroidism
• Severe physical or psychological concomitant diseases that might impair compliance with the provisions of the study protocol or that might impair the assessment of drug or patient safety, e.g. clinically significant ascites, cardiac failure, NYHA III or IV, clinically relevant pathologic findings in ECG
• Known hypersensitivity to zoledronic acid or other bisphosphonates
• Use of other investigational drugs 30 days prior to the date of randomization
• Known history or present abuse of alcohol or drugs
• Subjects who, in the opinion of the investigator, are unlikely to cooperate fully during the study
• Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.
• Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)

Other protocol defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
• To assess the relationship between change in bone parameters and bone scan with respect to bone metastases	Every 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Assessment of course of bone parameters (PINP, amino-terminal propeptide of procollagen type 1) and (ICTP, Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen)	Every 3 months
Assessment of course of Prostate-specific antigen (PSA)	Every 3 months
Assessment of correlation of bone parameters and PSA	Every 3 months
Assessment of optimal intervals for bone scans based on serum markers	Every 3 months
Assessment of time to rise in bone markers PINP and ICTP	Every 3 months
• Time to detection of bone metastases in bone scan	Every 3 months

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

General Publications

• Lein M, Miller K, Wirth M, Weissbach L, May C, Schmidt K, Haus U, Schrader M, Jung K. Bone turnover markers as predictive tools for skeletal complications in men with metastatic prostate cancer treated with zoledronic acid. Prostate. 2009 May 1;69(6):624-32. doi: 10.1002/pros.20917.

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: October 23, 2006
• First Submitted That Met QC Criteria: October 23, 2006
• First Posted (Estimate): October 24, 2006

Study Record Updates

• Last Update Posted (Estimate): November 18, 2016
• Last Update Submitted That Met QC Criteria: November 16, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Prostate cancer; Bisphosphonates; Serum bone marker; Early detection of metastasis
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Prostatic Neoplasms; Neoplasm Metastasis; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: CZOL446GDE22