Know Cancer

or
forgot password

A Randomized Double-Blind Placebo Controlled Phase III Trial Evaluating Zoledronate Plus Standard Therapy Versus Placebo Plus Standard Therapy in Patients With Recurrent Carcinoma of the Prostate Who Are Asymptomatic With Castrate Levels of Testosterone and Have Rising PSA Levels Without Radiologically-Evident Metastatic Disease


Phase 3
18 Years
N/A
Not Enrolling
Male
Prostate Cancer

Thank you

Trial Information

A Randomized Double-Blind Placebo Controlled Phase III Trial Evaluating Zoledronate Plus Standard Therapy Versus Placebo Plus Standard Therapy in Patients With Recurrent Carcinoma of the Prostate Who Are Asymptomatic With Castrate Levels of Testosterone and Have Rising PSA Levels Without Radiologically-Evident Metastatic Disease


OBJECTIVES: I. Compare the bone metastases free and overall survival in patients with
asymptomatic recurrent prostate cancer treated with zoledronate vs placebo at different time
points. II. Compare the time to first skeletal related events (pathological fractures,
surgery to prevent or treat pathological fractures, spinal cord compression, and
radiotherapy to bone) and skeletal morbidity rate in patients treated with these 2 regimens.
III. Assess quality of life and pain in these patients treated with these 2 regimens.

OUTLINE: This is a randomized, double blind, placebo controlled, open label, multicenter
study. Patients are stratified by prior local treatment (noncurative vs curative) and time
interval between surgical castration or initiation of LHRH agonists and trial entry (less
than 1 year vs 1-2 years vs greater than 2 years). Patients are randomized to 1 of 2
treatment arms: Arm I: Patients receive zoledronate IV over 15 minutes on day 1. Arm II:
Patients receive placebo IV over 15 minutes on day 1. Both arms: Treatment repeats every 4
weeks in the absence of documented bone metastasis, disease progression, or unacceptable
toxicity. All patients with documented bone metastases receive zoledronate as in arm I
through year 4. All patients receive oral calcium and oral vitamin D daily. Patients who
received LHRH agonists instead of surgical castration prior to study continue LHRH agonist
therapy during study. Quality of life and pain are assessed before each treatment. Patients
are followed every 6 months.

PROJECTED ACCRUAL: A total of 500 patients (250 per arm) will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically proven asymptomatic recurrent prostate cancer
Prior local treatment status Curatively treated OR Locally advanced disease noncuratively
treated with LHRH agonist therapy Currently receiving 1 line of hormonal therapy (with
LHRH agonists or surgical castration) and failing treatment with rising PSA only Patients
who received LHRH agonists instead of surgical castration continue to receive LHRH agonist
during study Biochemical progression documented by 3 consecutively rising PSA
measurements, each at least 2 weeks apart, with the last measurement being 50% or greater
than the nadir PSA achieved after the last therapeutic maneuver (first line hormonal
therapy as noted above) PSA (50% increased values) greater than 4 ng/mL for patients with
intact prostates and greater than 0.8 ng/mL for post-prostatectomy patients Rising PSA for
less than 10 months Castrate levels of testosterone (less than 30 ng/dL) No bone or
visceral metastases by bone scan and CT scan of abdomen and pelvis (except localized
abnormalities and pelvic lymph node and soft tissue disease) No CNS or leptomeningeal
involvement

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 90-100% Life
expectancy: Greater than 6 months Hematopoietic: WBC at least 3,000/mm3 Absolute
neutrophil count at least 1,500/mm3 Hemoglobin at least 8.0 g/dL Platelet count at least
75,000/mm3 Hepatic: Liver function tests no greater than 2.5 times upper limit of normal
(ULN) Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No New York Heart
Association class III or IV heart disease with uncontrolled and/or unstable cardiac or
coronary artery disease Other: No other malignancy within the past 5 years that would
confound the etiology of metastatic disease except curatively treated nonmelanomatous skin
cancer No other nonmalignant disease that would confound evaluation or preclude compliance
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior systemic biologic anticancer therapy
Chemotherapy: No prior chemotherapy Concurrent chemotherapy such as estramustine
containing regimens or mitoxantrone allowed at the discretion of the protocol investigator
Endocrine therapy: See Disease Characteristics No prior systemic hormonal anticancer
therapy except LHRH antagonists and/or nonsteroidal antiandrogens (e.g., flutamide,
bicalutamide, or nilutamide) Concurrent aminoglutethimide, prednisone, or
diethylstilbestrol or other estrogens allowed at the discretion of the protocol
investigator Radiotherapy: At least 6 weeks since prior palliative radiotherapy Surgery:
See Disease Characteristics Other: No other prior systemic anticancer therapy At least 4
weeks since other prior investigational drugs No other concurrent bisphosphonate agent

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

Fairooz F. Kabbinavar, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Jonsson Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

NOVARTIS-CZOL4460704

NCT ID:

NCT00005073

Start Date:

September 1999

Completion Date:

March 2003

Related Keywords:

  • Prostate Cancer
  • stage I prostate cancer
  • stage IIB prostate cancer
  • stage IIA prostate cancer
  • stage III prostate cancer
  • recurrent prostate cancer
  • Prostatic Neoplasms

Name

Location

Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781