search
Back to results

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

Primary Purpose

Metastatic Cancer, Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Doxorubicin hydrochloride
Goserelin acetate
Leuprolide acetate
Zoledronic acid
orchiectomy
strontium chloride Sr
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Cancer focused on measuring recurrent prostate cancer, stage IV prostate cancer, bone metastases

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria: Histologically or cytologically confirmed prostate carcinoma. Osteoblastic metastases on bone scan or computed tomography (CT) scan. Initiation of hormonal ablative therapy within 3 months of registration. Prior neoadjuvant, concurrent, or intermittent hormonal ablative therapy of less than 3 years duration and completed at least 3 years prior to entry into this study. The Eastern Cooperative Oncology Group (ECOG) performance status <3 (Karnofsky >40%) Patients must have normal organ and marrow function as defined: leukocytes: >3,000/mL; absolute neutrophil count: >1,500/mL; platelets: >100,000/mL; total bilirubin within normal institutional limits; alanine transaminase (ALT)(SGPT)/aspartate aminotransferase (AST)(SGOT): <2.5 * institutional upper limit of normal; creatinine: < or = 3.0; left ventricular ejection fraction: >45% The effects of strontium-89 and zoledronic acid on the developing human fetus at the recommended therapeutic dose are unknown. Even though all patients are castrated during this study, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should the spouse of a patient become pregnant or suspect she is pregnant while participating in this study, she/he should inform the treating physician immediately. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: More than one prior chemotherapy regimen. Prior doxorubicin treatment is permitted. However patient's with >250 mg/m2 cumulative dosage are excluded. Prior radioisotope treatment consisting of strontium-89 or samarium-153. Zoledronic acid treatment for more than 3 months duration prior to registration. Other bisphosphonate treatments are permitted. Corrected serum calcium level less than 8 mg/dL. Patients may not be receiving any other investigational agents. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. History of allergic reactions attributed to compounds of similar chemical or biologic composition to zoledronic acid or other agents used in the study Patients with the following atypical presentations should have a biopsy: those with small cell carcinoma, purely lytic bone metastases, or bulky (i.e. 5 cm) visceral or nodal disease in the absence of bone involvement are not eligible. Symptomatic bulky lymphadenopathy causing scrotal or pedal edema or significant local invasive disease in bladder invasion. History of other malignancies other than nonmelanoma skin cancer, unless in complete remission and off therapy for that disease for at least 5 years. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with strontium-89 or other agents administered during the study. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated. Evidence or suspicion of myelodysplastic syndrome by complete blood test (CBC) must be confirmed by bone marrow biopsy. Untreated symptomatic spinal cord compressions.

Sites / Locations

  • M.D. Anderson Cancer Center at Orlando
  • CCOP - Wichita
  • M.D. Anderson Cancer Center at University of Texas
  • CCOP - Marshfield Clinic Research Foundation

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

HAT, Doxorubicin, Zoledronate + Strontium chloride

HAT, Doxorubicin + Zoledronate

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS)
Study's primary endpoint of PFS duration/time to progression was defined as the time from the date of randomization to the date of first evidence of disease progression or patient death. Prostate-specific antigen (PSA) progression is usually the first evidence of progression. PSA progression is defined as a 25% increase over the baseline or the nadir provided that the increase is a minimum of 1 ng/ml.

Secondary Outcome Measures

Major Bone Scan Response
Bone scan performed at baseline and at Week 13 provided if baseline scan was positive for metastases. A major bone scan response was considered with a substantial resolution of participant bone metastases on the bone scans, i.e. complete resolution of the osseous metastases on the bone scan.

Full Information

First Posted
April 7, 2004
Last Updated
September 22, 2016
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00081159
Brief Title
Hormone Ablation Therapy, Doxorubicin, and Zoledronate With or Without Strontium 89 in Treating Patients With Androgen-Dependent Prostate Cancer and Bone Metastases
Official Title
A Randomized Phase II Study Of Bone-Targeted Therapy In Advanced Androgen-Dependent Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
July 2004 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Cancer, Prostate Cancer
Keywords
recurrent prostate cancer, stage IV prostate cancer, bone metastases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HAT, Doxorubicin, Zoledronate + Strontium chloride
Arm Type
Experimental
Arm Description
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.
Arm Title
HAT, Doxorubicin + Zoledronate
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin hydrochloride
Other Intervention Name(s)
Adriamycin PFS, Adriamycin RDF, Adriamycin, Rubex
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Goserelin acetate
Other Intervention Name(s)
Zoladex
Intervention Type
Drug
Intervention Name(s)
Leuprolide acetate
Other Intervention Name(s)
Lupron Depot
Intervention Type
Drug
Intervention Name(s)
Zoledronic acid
Other Intervention Name(s)
Zoledronate, Zometa
Intervention Description
4 mg given intravenously over 15 minutes every 28 days for a total of 6 doses.
Intervention Type
Procedure
Intervention Name(s)
orchiectomy
Intervention Type
Radiation
Intervention Name(s)
strontium chloride Sr
Other Intervention Name(s)
Sr-89, Strontium-89, Mestastron
Intervention Description
1 dose of strontium-89 (4 millicurie (mCi) total dose) administered intravenously on the first day of treatment
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
Study's primary endpoint of PFS duration/time to progression was defined as the time from the date of randomization to the date of first evidence of disease progression or patient death. Prostate-specific antigen (PSA) progression is usually the first evidence of progression. PSA progression is defined as a 25% increase over the baseline or the nadir provided that the increase is a minimum of 1 ng/ml.
Time Frame
Up to 90 months with evaulation in 4 week intervals for up to 6 months of treatment, then follow up until disease progression
Secondary Outcome Measure Information:
Title
Major Bone Scan Response
Description
Bone scan performed at baseline and at Week 13 provided if baseline scan was positive for metastases. A major bone scan response was considered with a substantial resolution of participant bone metastases on the bone scans, i.e. complete resolution of the osseous metastases on the bone scan.
Time Frame
Week 13
Other Pre-specified Outcome Measures:
Title
Overall Survival (OS)
Description
Overall Survival defined as the length of time from the start of treatment till time that participants are still alive.
Time Frame
Up to 90 months

10. Eligibility

Sex
Male
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed prostate carcinoma. Osteoblastic metastases on bone scan or computed tomography (CT) scan. Initiation of hormonal ablative therapy within 3 months of registration. Prior neoadjuvant, concurrent, or intermittent hormonal ablative therapy of less than 3 years duration and completed at least 3 years prior to entry into this study. The Eastern Cooperative Oncology Group (ECOG) performance status <3 (Karnofsky >40%) Patients must have normal organ and marrow function as defined: leukocytes: >3,000/mL; absolute neutrophil count: >1,500/mL; platelets: >100,000/mL; total bilirubin within normal institutional limits; alanine transaminase (ALT)(SGPT)/aspartate aminotransferase (AST)(SGOT): <2.5 * institutional upper limit of normal; creatinine: < or = 3.0; left ventricular ejection fraction: >45% The effects of strontium-89 and zoledronic acid on the developing human fetus at the recommended therapeutic dose are unknown. Even though all patients are castrated during this study, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should the spouse of a patient become pregnant or suspect she is pregnant while participating in this study, she/he should inform the treating physician immediately. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: More than one prior chemotherapy regimen. Prior doxorubicin treatment is permitted. However patient's with >250 mg/m2 cumulative dosage are excluded. Prior radioisotope treatment consisting of strontium-89 or samarium-153. Zoledronic acid treatment for more than 3 months duration prior to registration. Other bisphosphonate treatments are permitted. Corrected serum calcium level less than 8 mg/dL. Patients may not be receiving any other investigational agents. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. History of allergic reactions attributed to compounds of similar chemical or biologic composition to zoledronic acid or other agents used in the study Patients with the following atypical presentations should have a biopsy: those with small cell carcinoma, purely lytic bone metastases, or bulky (i.e. 5 cm) visceral or nodal disease in the absence of bone involvement are not eligible. Symptomatic bulky lymphadenopathy causing scrotal or pedal edema or significant local invasive disease in bladder invasion. History of other malignancies other than nonmelanoma skin cancer, unless in complete remission and off therapy for that disease for at least 5 years. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with strontium-89 or other agents administered during the study. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated. Evidence or suspicion of myelodysplastic syndrome by complete blood test (CBC) must be confirmed by bone marrow biopsy. Untreated symptomatic spinal cord compressions.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shi-Ming Tu, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
M.D. Anderson Cancer Center at Orlando
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806-2134
Country
United States
Facility Name
CCOP - Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214-3882
Country
United States
Facility Name
M.D. Anderson Cancer Center at University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
CCOP - Marshfield Clinic Research Foundation
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website

Learn more about this trial

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

We'll reach out to this number within 24 hrs