Clinical trial NCT00685646: Androgen Blockade Therapy With or Without Zoledronic Acid in Treating Patients With Prostate Cancer and Bone Metastases
Official title: A Phase III, Multicenter, Randomized, Controlled Study of Maximum Androgen Blockade With vs. Without Zoledronic Acid in Prostatic Cancer Patients With Metastatic Bone Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Cancer
Prostate Cancer
Keywords: bone metastases
stage IV prostate cancer
Lead sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
Sponsor class: OTHER
Collaborators: name: Kyoto University, Graduate School of Medicine
First posted: 2008-05-28
Enrollment: 227
Sex: MALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to treatment failure (TTF)
timeFrame: 6 years
Secondary outcomes:
measure: Time to first skeletal-related events (SRE)
timeFrame: 6 years
measure: Overall survival
timeFrame: 6 years
measure: Extent of disease on bone scan (EOD)
timeFrame: Baseline, Month 12, 24 and 36
measure: Pain scale
timeFrame: Baseline, Month 12, 24 and 36
measure: FACES pain-rating scale
timeFrame: Baseline, Month 12, 24 and 36
measure: Adverse events
timeFrame: Month 6, 12, 18, 24 and 30
measure: QOL (SF-36)
timeFrame: Month 6, 12, 18, 24, 30 and 36
Other outcomes:
Locations:
city: Kyoto
country: Japan
facility: Kyoto University Hospital
Study officials:
affiliation: Kyoto University, Graduate School of Medicine
name: Osamu Ogawa, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.