Hormone Ablation Therapy, Doxorubicin, and Zoledronate With or Without Strontium 89 in Treating Patients With Androgen-Dependent Prostate Cancer and Bone Metastases
This study is ongoing, but not recruiting participants.
Sponsor:
M.D. Anderson Cancer Center
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00081159
First received: April 7, 2004
Last updated: October 24, 2012
Last verified: October 2012
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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 acetate Drug: Leuprolide acetate Drug: Zoledronic acid Procedure: orchiectomy Radiation: strontium chloride Sr |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Randomized Phase II Study Of Bone-Targeted Therapy In Advanced Androgen-Dependent Prostate Cancer |
Resource links provided by NLM:
Drug Information available for:
Chlorine
Doxorubicin
Doxorubicin hydrochloride
Strontium chloride Sr 89
Goserelin
Leuprolide acetate
Zoledronic acid
Goserelin acetate
U.S. FDA Resources
Further study details as provided by M.D. Anderson Cancer Center:
Primary Outcome Measures:
- Time to progression [ Time Frame: 4 week intervals, up to 6 months of treatment, then follow up until disease progression ] [ Designated as safety issue: No ]Time to progression defined as the duration of time from start of treatment to disease progression.
Secondary Outcome Measures:
- Major bone scan response [ Time Frame: Week 13 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 80 |
| Study Start Date: | August 2004 |
| Estimated Primary Completion Date: | May 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: HAT, Doxorubicin, Zoledronate + Strontium chloride
Arm I: Hormonal ablative therapy (HAT) comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; 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.
|
Drug: Doxorubicin hydrochloride
Doxorubicin 20 mg/m^2 is administered intravenously either over 15 to 30 minutes via a peripheral line or over 24 hours via a central line on days 1, 8, and 15 every 28 days for 2 cycles.
Other Names:
Drug: Goserelin acetate
Other Name: Zoladex
Drug: Leuprolide acetate
Other Name: Lupron Depot
Drug: Zoledronic acid
4 mg given intravenously over 15 minutes every 28 days for a total of 6 doses.
Other Names:
Procedure: orchiectomy
Radiation: strontium chloride Sr
1 dose of strontium-89 (4 millicurie (mCi) total dose) administered intravenously on the first day of treatment
Other Names:
|
|
Experimental: HAT, Doxorubicin + Zoledronate
Arm II: HAT, doxorubicin, and zoledronate as in arm I. HAT comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; 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.
|
Drug: Doxorubicin hydrochloride
Doxorubicin 20 mg/m^2 is administered intravenously either over 15 to 30 minutes via a peripheral line or over 24 hours via a central line on days 1, 8, and 15 every 28 days for 2 cycles.
Other Names:
Drug: Goserelin acetate
Other Name: Zoladex
Drug: Leuprolide acetate
Other Name: Lupron Depot
Drug: Zoledronic acid
4 mg given intravenously over 15 minutes every 28 days for a total of 6 doses.
Other Names:
Procedure: orchiectomy
|
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 versus > 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 intravenously (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 computed tomography (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
- Eastern Cooperative Oncology Group (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
- White Blood Count (WBC) ≥ 3,000/mm^3
Hepatic
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal
- Bilirubin normal
Renal
- Creatinine ≤ 3.0 mg/dL
- Calcium level ≥ 8 mg/dL
Cardiovascular
- Left Ventricular Ejection Fraction (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
Investigators
| Study Chair: | Shi-Ming Tu, MD | M.D. Anderson Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00081159 History of Changes |
| Other Study ID Numbers: | CDR0000360625, MDA-2003-0922, NCI-6459 |
| Study First Received: | April 7, 2004 |
| Last Updated: | October 24, 2012 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by M.D. Anderson Cancer Center:
|
recurrent prostate cancer stage IV prostate cancer bone metastases |
Additional relevant MeSH terms:
|
Neoplasm Metastasis Neoplasms Neoplasms, Second Primary Prostatic Neoplasms Neoplastic Processes Pathologic Processes Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Genital Diseases, Male Prostatic Diseases Androgens Doxorubicin Leuprolide |
Goserelin Zoledronic acid Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Antineoplastic Agents, Hormonal Fertility Agents, Female Fertility Agents Reproductive Control Agents Bone Density Conservation Agents |
ClinicalTrials.gov processed this record on May 19, 2013