Metastatic CancerPhase 2NCT00081159
Hormone Ablation Therapy, Doxorubicin, and Zoledronate With or Without Strontium 89 in Treating Patients With Androgen-Dependent Prostate Cancer and Bone Metastases
A Phase 2 study testing Doxorubicin hydrochloride, Goserelin acetate and Leuprolide acetate in people with Metastatic Cancer and Prostate Cancer, run by M.D. Anderson Cancer Center at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Metastatic Cancer, Prostate Cancer
- What is being tested?
- Doxorubicin hydrochloride, Goserelin acetate and Leuprolide acetate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 4 sitesUnited States
- Study dates
- Jul 2004to Sep 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, 54449
M.D. Anderson Cancer Center at Orlando
Orlando, Florida, 32806-2134
CCOP - Wichita
Wichita, Kansas, 67214-3882
About this study
Official title: A Randomized Phase II Study Of Bone-Targeted Therapy In Advanced Androgen-Dependent Prostate Cancer
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.
Read the 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.
- Conditions
- Metastatic Cancer, Prostate Cancer
- Being tested
- Doxorubicin hydrochloride, Goserelin acetate, Leuprolide acetate, Zoledronic acid, orchiectomy
- Keywords
- recurrent prostate cancer, stage IV prostate cancer, bone metastases
- Medical subject headings
- Neoplasm Metastasis, Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Adriamycin PFS, Adriamycin RDF, Adriamycin, Rubex
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.
Goserelin acetateDrug
Also called Zoladex
Leuprolide acetateDrug
Also called Lupron Depot
Zoledronic acidDrug
Also called Zoledronate, Zometa
4 mg given intravenously over 15 minutes every 28 days for a total of 6 doses.
orchiectomyProcedure or surgery
strontium chloride SrRadiation
Also called Sr-89, Strontium-89, Mestastron
1 dose of strontium-89 (4 millicurie (mCi) total dose) administered intravenously on the first day of treatment
| Study group | Role | What they receive |
|---|---|---|
| HAT, Doxorubicin, Zoledronate + Strontium chloride | Experimental | 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. Receives: Drug: Doxorubicin hydrochloride; Drug: Goserelin acetate; Drug: Leuprolide acetate; Drug: Zoledronic acid; Procedure: orchiectomy; Radiation: strontium chloride Sr |
| HAT, Doxorubicin + Zoledronate | Experimental | 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. Receives: Drug: Doxorubicin hydrochloride; Drug: Goserelin acetate; Drug: Leuprolide acetate; Drug: Zoledronic acid; Procedure: orchiectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 90 months with evaulation in 4 week intervals for up to 6 months of treatment, then follow up until disease progression
Secondary outcomes (1)
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.
Measured: Week 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2004 (estimated)
- Study startJul 2004
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Shi-Ming Tu, MD, Study chair, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00081159
- Sponsor's protocol ID
- 2003-0922
- Other IDs
- MDA-2003-0922, NCI-6459, NCI-2009-00062, CDR0000360625, 2U10CA045809-17
- Status last verified
- Sep 2016
- First submitted
- 7 Apr 2004
- Last updated
- 10 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study Of Bone-Targeted Therapy In Advanced Androgen-Dependent Prostate Cancer
- ClinicalTrials.gov ID
- NCT00081159
- Acronym / sponsor ID
- 2003-0922
- Conditions
- Metastatic Cancer, Prostate Cancer
- Keywords
- recurrent prostate cancer, stage IV prostate cancer, bone metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2004
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 8 Apr 2004 (estimated)
- Results
- Posted 10 Nov 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HAT, Doxorubicin, Zoledronate + Strontium chloride | Experimental | Drug: Doxorubicin hydrochloride, Drug: Goserelin acetate, Drug: Leuprolide acetate, Drug: Zoledronic acid, Procedure: orchiectomy, Radiation: strontium chloride SrArm 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. |
| HAT, Doxorubicin + Zoledronate | Experimental | Drug: Doxorubicin hydrochloride, Drug: Goserelin acetate, Drug: Leuprolide acetate, Drug: Zoledronic acid, Procedure: orchiectomyArm 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. |
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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%)
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Doxorubicin hydrochlorideAlso: Adriamycin PFS, Adriamycin RDF, Adriamycin, RubexDoxorubicin 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. | Drug | HAT, Doxorubicin + Zoledronate, HAT, Doxorubicin, Zoledronate + Strontium chloride |
| Goserelin acetateAlso: Zoladex | Drug | HAT, Doxorubicin + Zoledronate, HAT, Doxorubicin, Zoledronate + Strontium chloride |
| Leuprolide acetateAlso: Lupron Depot | Drug | HAT, Doxorubicin + Zoledronate, HAT, Doxorubicin, Zoledronate + Strontium chloride |
| Zoledronic acidAlso: Zoledronate, Zometa4 mg given intravenously over 15 minutes every 28 days for a total of 6 doses. | Drug | HAT, Doxorubicin + Zoledronate, HAT, Doxorubicin, Zoledronate + Strontium chloride |
| orchiectomy | Procedure or surgery | HAT, Doxorubicin + Zoledronate, HAT, Doxorubicin, Zoledronate + Strontium chloride |
| strontium chloride SrAlso: Sr-89, Strontium-89, Mestastron1 dose of strontium-89 (4 millicurie (mCi) total dose) administered intravenously on the first day of treatment | Radiation | HAT, Doxorubicin, Zoledronate + Strontium chloride |
Primary outcome
Progression Free Survival (PFS)
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
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.
1 secondary outcome
Major Bone Scan Response
Time frame: Week 13
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shi-Ming Tu, MD study chair
M.D. Anderson Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Doxorubicin hydrochloride, Goserelin acetate and Leuprolide acetate in people with Metastatic Cancer and Prostate Cancer, run by M.D. Anderson Cancer Center at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2016.