Androgen Blockade Therapy With or Without Zoledronic Acid in Treating Patients With Prostate Cancer and Bone Metastases (ZAPCA)

A Phase III, Multicenter, Randomized, Controlled Study of Maximum Androgen Blockade With vs. Without Zoledronic Acid in Prostatic Cancer Patients With Metastatic Bone Disease

RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen blockade therapy may lessen the amount of androgens made by the body. Zoledronic acid may help relieve some of the symptoms caused by bone metastasis. It is not yet known whether androgen-blockade therapy is more effective with or without zoledronic acid in treating patients with prostate cancer that has spread to the bone.

PURPOSE: This randomized phase III trial is studying androgen-blockade therapy given together with zoledronic acid to see how well it works compared with androgen-blockade therapy alone in treating patients with prostate cancer and bone metastases.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Metastatic Cancer
• Intervention / Treatment: Drug: antiandrogen therapy; Drug: zoledronic acid

Detailed Description

OBJECTIVES:

• Evaluate the time to treatment failure in prostatic cancer patients with metastatic bone disease receiving maximum androgen-blockade therapy with vs without zoledronic acid.
• Evaluate the time to first skeletal-related events in these patients.
• Evaluate the overall survival of these patients.
• Evaluate the extent of disease on bone scan in these patients.
• Evaluate the pain scale and FACES pain-rating scale in these patients.
• Evaluate the safety of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive maximum androgen-blockade therapy and zoledronic acid for up to 24 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive maximum androgen-blockade therapy for up to 24 courses in the absence of disease progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Patients with definitive diagnosis of prostatic cancer by histopathological diagnosis or cytology
• Androgen blockade therapy-, systemic chemotherapy-, bisphosphonates-naïve prostatic cancer patients
• Patients who are sensitive to androgen blockade therapy
• Patients with bone metastasis on bone scan (EOD ≥ 1)
• Patients who have Eastern Cooperative Oncology Group performance status (ECOG: 0-2)
• Patients who have prostate-specific antigen performance status (PSA ≧30 ng/mL)

• Patients who demonstrate appropriate bone marrow, hepatic and renal functions in laboratory tests within four weeks before the registration.

  • Leukocyte count ≥ 3,000/μL
  • Hemoglobin ≥ 9.0 g/dL
  • Platelet count ≥ 7.5 × 10^4/μL
  • Serum creatine level ≤ 3.0 mg/dL
  • 8.5 mg/dL ≤ corrected serum level of calcium ≤ 11.5 mg/dL
  • Total bilirubin ≤ 1.8 mg/dL
  • Aspartate aminotransferase (AST) Levels ≤ 90 IU/L
  • Alanine aminotransferase (ALT) Levels ≤ 100 IU/L
  • Patients who agreed to participate in this clinical study in writing after receiving sufficient explanation

Exclusion criteria:

• Patients with poorly-controlled dental caries
• Patients with double cancer that requires treatment
• Patients who are using following steroid drugs (except for topical ointment)
• Patients with poorly-controlled hypertension or cardiovascular disease
• Patients with active infectious diseases or HIV or hepatitis virus infections
• Other patients whose participation in the present study is considered inappropriate by a Principal Investigator or Clinical Investigator

PRIOR CONCURRENT THERAPY:

• No prior androgen-blockade therapy
• No prior or other concurrent anticancer therapy
• No prior or concurrent immunologic adjuvant therapy
• No prior or concurrent steroid drugs (except ointment)
• No other prior or concurrent bisphosphonates (excluding zoledronic acid)
• No prior systemic chemotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive maximum androgen-blockade therapy and zoledronic acid for up to 24 courses.	Drug: antiandrogen therapy; Up to 24 courses of therapy; Drug: zoledronic acid; Up to 24 courses of therapy
Active Comparator: Arm II; Patients receive maximum androgen-blockade therapy for up to 24 courses.	Drug: antiandrogen therapy; Up to 24 courses of therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to treatment failure (TTF)	The interval from the date of randomization to the earliest date on which prostate-specific antigen (PSA) progression, clinical progression, first skeletal-related events (SRE), death, or cessation of protocol treatment for any reason occurred.	6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first skeletal-related events (SRE)	The interval from the date of randomization to the earliest date of the first SRE or death for any reason. But exlude tha another SRE existing case on the same region as of the randomization.	6 years
Overall survival	The interval from the date of randomization to death for any reason.	6 years
Extent of disease on bone scan (EOD)	Ransition of EOD bone scan grade at randomization, 12, 24, 36 months after the therapy.	Baseline, Month 12, 24 and 36
Pain scale	Ransition of with/without narcotic drug usage at randomization, 12, 24, 36 months after the therapy and if the case of without usage, ransition of rest pain scale.	Baseline, Month 12, 24 and 36
FACES pain-rating scale	Ransition of FACES pain-rating scale at randomization, 12, 24, 36 months after the therapy.	Baseline, Month 12, 24 and 36
Adverse events	Adverse events from date of starting protocol treatment until 28 days after date of finishing the treatment are evaluated according to Japanese version of the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) by Translational Research Informatics Center.	Month 6, 12, 18, 24 and 30
QOL (SF-36)	Rantision of QOL health survey scale durintg protocol treatment.	Month 6, 12, 18, 24, 30 and 36

Collaborators and Investigators

• Sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
• Collaborators: Kyoto University, Graduate School of Medicine
• Investigators: Principal Investigator: Osamu Ogawa, MD, Ph.D., Kyoto University, Graduate School of Medicine

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: May 22, 2008
• First Submitted That Met QC Criteria: May 24, 2008
• First Posted (Estimate): May 28, 2008

Study Record Updates

• Last Update Posted (Estimate): October 16, 2015
• Last Update Submitted That Met QC Criteria: October 15, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: stage IV prostate cancer; bone metastases
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Bone Density Conservation Agents; Zoledronic Acid; Androgen Antagonists
• Other Study ID Numbers: TRIGU0705; KYUH-TRIGU0705 (Other Identifier: National Cancer Institute)