Hormone Ablation Therapy, Doxorubicin, and Zoledronate With or Without Strontium 89 in Treating Patients With Androgen-Dependent Prostate Cancer and Bone Metastases - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00081159

Purpose

RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as goserelin and leuprolide may fight prostate cancer by stopping the adrenal glands from producing androgens. Drugs used in chemotherapy such as doxorubicin work in different ways to stop tumor cells from dividing so they stop growing or die. Zoledronate may prevent bone loss and stop the growth of tumor cells in bone. Radioactive substances such as strontium-89 may relieve bone pain associated with prostate cancer. It is not yet known whether hormone (androgen) ablation therapy and chemotherapy combined with zoledronate is more effective with or without strontium-89 in treating prostate cancer and bone metastases.

PURPOSE: This randomized phase II trial is studying giving hormone ablation therapy, doxorubicin, and zoledronate together with strontium-89 to see how well it works compared to hormone ablation therapy, doxorubicin, and zoledronate alone in treating patients with androgen-dependent prostate cancer and bone metastases.

Condition	Intervention	Phase
Metastatic Cancer Prostate Cancer	Drug: doxorubicin hydrochloride Drug: goserelin Drug: leuprolide acetate Drug: zoledronic acid Procedure: orchiectomy Radiation: strontium chloride Sr 89	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Randomized Phase II Study Of Bone-Targeted Therapy In Advanced Androgen-Dependent Prostate Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Doxorubicin Strontium chloride Sr 85 Doxorubicin hydrochloride Strontium chloride Sr 89 Leuprolide Goserelin Leuprolide acetate Myocet Zoledronic acid Strontium

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Time to progression [ Designated as safety issue: No ]

Secondary Outcome Measures:

Major bone scan response [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	August 2004

Detailed Description:

OBJECTIVES:

Primary

Compare the clinical efficacy of hormonal ablative therapy combined with doxorubicin and zoledronate with or without strontium chloride Sr 89, in terms of progression-free survival, in patients with androgen-dependent prostate cancer and bone metastases.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to the number of bony metastases (≤ 6 vs > 6). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive hormonal ablative therapy comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy. Patients also receive doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses; and a single dose of strontium chloride Sr 89 IV over 1-2 minutes on day 1.
Arm II: Patients receive hormonal ablative therapy, doxorubicin, and zoledronate as in arm I.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 80 patients (40 per treatment arm) will be accrued for this study within 20 months.

Eligibility

Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed prostate cancer
- Osteoblastic metastases on bone scan or CT scan
Androgen-dependent disease
- Previously treated with neoadjuvant or intermittent hormonal ablative therapy* at least 3 years ago AND has reinitiated hormonal ablative therapy within 3 months before study entry NOTE: *Therapy was less than 3 years in duration
No symptomatic bulky lymphadenopathy causing scrotal or pedal edema
No significant local invasive disease with bladder invasion
No evidence or suspicion of myelodysplastic syndromes by complete blood count and bone marrow biopsy
No small cell carcinoma, purely lytic bone metastasis, or bulky (i.e., ≥ 5 cm) visceral or nodal disease in the absence of bone involvement by biopsy
No known brain metastases

PATIENT CHARACTERISTICS:

Age

Not specified

Performance status

ECOG 0-3 OR
Karnofsky 40-100%

Life expectancy

More than 3 months

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
WBC ≥ 3,000/mm^3

Hepatic

AST and ALT ≤ 2.5 times upper limit of normal
Bilirubin normal

Renal

Creatinine ≤ 3.0 mg/dL
Calcium level ≥ 8 mg/dL

Cardiovascular

LVEF ≥ 45%
No history of congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Other

Fertile patients must use effective contraception
No prior allergic reaction attributed to compounds of similar chemical or biological composition to zoledronate or other study drugs
No other malignancy within the past 5 years except nonmelanoma skin cancer
No active or ongoing infection
No psychiatric illness or social situation that would preclude study compliance
No untreated symptomatic spinal cord compressions
No other concurrent uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Prior doxorubicin allowed provided the cumulative dosage was ≤ 250 mg/m^2
No more than 1 prior chemotherapy regimen

Endocrine therapy

See Disease Characteristics

Radiotherapy

No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium

Surgery

Not specified

Other

Prior zoledronate allowed provided treatment was no more than 3 months in duration
Other prior bisphosphonates allowed
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent investigational agents
No other concurrent anticancer therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00081159

Locations

United States, Florida
M.D. Anderson Cancer Center at Orlando
Orlando, Florida, United States, 32806-2134
United States, Kansas
CCOP - Wichita
Wichita, Kansas, United States, 67214-3882
United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
United States, Wisconsin
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Shi-Ming Tu, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000360625, MDA-2003-0922, NCI-6459
Study First Received:	April 7, 2004
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00081159 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent prostate cancer
stage IV prostate cancer
bone metastases

Additional relevant MeSH terms:

Prostatic Diseases
Genital Neoplasms, Male
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents
Urogenital Neoplasms
Reproductive Control Agents
Antibiotics, Antineoplastic
Hormones
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Leuprolide

Therapeutic Uses
Neoplasm Metastasis
Zoledronic acid
Antineoplastic Agents, Hormonal
Goserelin
Genital Diseases, Male
Doxorubicin
Pharmacologic Actions
Neoplasms
Fertility Agents, Female
Fertility Agents
Prostatic Neoplasms
Androgens

ClinicalTrials.gov processed this record on November 09, 2009