Prostatic NeoplasmsPhase 2NCT00447473
Trial of GM-CSF Given in Combination With Ketoconazole and Mitoxantrone in Patients With Progressive Prostate Cancer
A Phase 2 study testing GM-CSF, Ketoconazole and Mitoxantrone in people with Prostatic Neoplasms, run by The Methodist Hospital Research Institute at 1 site in United States.
Trial summary
This trial represents an attempt to offer second line immunotherapy plus chemotherapy to patients who have failed prior taxane base therapy. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- GM-CSF, Ketoconazole and Mitoxantrone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2006to Sep 2008
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
- Histologically confirmed adenocarcinoma of the prostate
- Testosterone < 50 ng/dL. Patients must continue primary androgen deprivation with an LHRH analogue if they have not undergone orchiectomy.
- Progressive disease after androgen deprivation.
- Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen.
- Karnofsky Performance Status ≥ 60%.
- One prior taxane based chemotherapy for prostate cancer. No more than two prior systemic therapies. At least four weeks have lapsed since prior therapy.
- Patients may have had prior ketoconazole, aminoglutethimide or corticosteroids for treatment of progressive prostate cancer.
- Patients receiving any other hormonal therapy, including any dose of megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid must discontinue the agent for at least 4 weeks prior to enrollment. Progressive disease must be documented after discontinuation of the hormonal therapy.
- Patients on stable doses of bisphosphonates that show subsequent tumor progression may continue on this medication; however, patients are not allowed to initiate bisphosphonate therapy within one month prior to starting therapy or throughout the study.
- Liver function tests (ALT, AST) less than 1.5 x upper limit of normal (ULN). The bilirubin must be within normal limits.
- ANC >1500/µl, Platelet count > 100,00/µl, Creatinine <1.5 x ULN, Hemoglobin > 8 mg/dl
- Ejection fraction ≥45%.
Trial locations and contacts
1 site in 1 country.
United States1 site
Baylor College of Medicine - Methodist Hospital
Houston, Texas, 77030
About this study
Official title: Phase II Trial to Assess the Activity of Ketoconazole and Mitoxantrone Plus GM-CSF in Patients With Progressive Hormone Refractory Prostate Cancer
This trial represents an attempt to offer second line immunotherapy plus chemotherapy to patients who have failed prior taxane base therapy.
Read the detailed description
Prostate cancer is the second leading cause of cancer death in American men. Hormonal ablation, in the form of medical or surgical castration is the cornerstone of management for metastatic prostate cancer however, treatment options for a patient in whom androgen ablation fails are limited. Second-line hormonal agents are generally associated with low response rates and no documented survival benefit.
A variety of taxane-based regimens have been tested in hormone refractory prostate cancer, yielding response rates between 38% - 69%. As responses to taxane-based regimens have appeared to exceed those typically associated with mitoxantrone plus prednisone, taxane-based therapy has been widely used in the community, typically as first line therapy. Second line therapy, which are non-taxane based and have comparable activities do not exist.
This study builds on experience in drug development for advanced prostate cancer demonstrating the following:
- Ketoconazole produces serologic and objective clinical responses in over 50% of patients with disease progression on oral antiandrogen.
- GM-CSF, as a potent stimulator of dendritic cells, has demonstrated clinical activity in prostate cancer.
- GM-CSF is well tolerated in patients with prostate cancer. The addition of GM-CSF to antitumor therapy may augment the T cell response to apoptotic tumor cells and therefore may improve the clinical benefit produced by such agents.
- The addition of mitoxantrone with ketoconazole demonstrated improved clinical benefit relative to the published data with each single agent.
The importance of this trial in the broader context of clinical research for prostate cancer is twofold: One, it represents an attempt to offer second line immunotherapy plus chemotherapy to patients who have failed prior frontline taxane based therapy. Two, this is the first trial to assess the combination of GM-CSF plus ketoconazole and mitoxantrone.
- Conditions
- Prostatic Neoplasms
- Being tested
- GM-CSF, Ketoconazole, Mitoxantrone
- Keywords
- Prostate Cancer, progressive hormone refractory prostate cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GM-CSFDrug
Also called Leukine
GM-CSF will be administered as a subcutaneous injection at a dose of 250mcg/m2/d (maximum 500 mcg) on weeks 2 and 3 each 21 day cycle (total of 14 days).
KetoconazoleDrug
Also called Nizoral, Extina, Xolegel, Kuric
Ketoconazole will be administered daily at a dose of 400 mg po tid (either 1 hour before or 2 hours after meals), ascorbic acid 250 mg po tid (given with ketoconazole) and replacement doses of hydrocortisone (20 mg po in the morning and 10 mg po in the evening).
MitoxantroneDrug
Also called Novantrone, Mitoxantrone
Mitoxantrone will be given at dose of 12 mg/m2 every 3 weeks, up to a maximum cumulative dose of 140 mg/m2
| Study group | Role | What they receive |
|---|---|---|
| A | Other | GM-CSF given in combination with ketoconazole and mitoxantrone in patients with progressive prostate cancer despite androgen deprivation and prior taxane containing chemotherapy Receives: Drug: GM-CSF; Drug: Ketoconazole; Drug: Mitoxantrone |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the effect of the combination of ketoconazole and mitoxantrone plus GM-CSF on time to clinical progression in patients with prostate cancer that has progressed on prior therapy.
Measured: restaged every 9 weeks
Secondary outcomes (2)
To evaluate the objective response frequency of the combination of ketoconazole and mitoxantrone plus GM-CSF.
Measured: restaged every 9 weeks
To investigate the safety of ketoconazole and mitoxantrone given in combination with GM-CSF.
Measured: AE reporting as occurs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2007 (estimated)
- Study startJul 2006
- Primary completionAug 2008
- Study completionSep 2008
Why it stopped: PI decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- More trials run by The Methodist Hospital Research InstituteThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Robert J Amato, DO, Principal investigator, Baylor College of Medicine - Methodist Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00447473
- Sponsor's protocol ID
- HMRI IRB#0106-0010
- Other IDs
- PC-Keto-Mito.2006
- Status last verified
- Mar 2016
- First submitted
- 12 Mar 2007
- Last updated
- 17 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial to Assess the Activity of Ketoconazole and Mitoxantrone Plus GM-CSF in Patients With Progressive Hormone Refractory Prostate Cancer
- ClinicalTrials.gov ID
- NCT00447473
- Acronym / sponsor ID
- HMRI IRB#0106-0010
- Conditions
- Prostatic Neoplasms
- Keywords
- Prostate Cancer, progressive hormone refractory prostate cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI decision
- Enrolment
- 31 participants (actual)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Jul 2006
- Primary completion
- Aug 2008 (actual)
- Study completion
- Sep 2008 (actual)
- First posted
- 14 Mar 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial represents an attempt to offer second line immunotherapy plus chemotherapy to patients who have failed prior taxane base therapy.
Detailed description
Prostate cancer is the second leading cause of cancer death in American men. Hormonal ablation, in the form of medical or surgical castration is the cornerstone of management for metastatic prostate cancer however, treatment options for a patient in whom androgen ablation fails are limited. Second-line hormonal agents are generally associated with low response rates and no documented survival benefit.
A variety of taxane-based regimens have been tested in hormone refractory prostate cancer, yielding response rates between 38% - 69%. As responses to taxane-based regimens have appeared to exceed those typically associated with mitoxantrone plus prednisone, taxane-based therapy has been widely used in the community, typically as first line therapy. Second line therapy, which are non-taxane based and have comparable activities do not exist.
This study builds on experience in drug development for advanced prostate cancer demonstrating the following:
- Ketoconazole produces serologic and objective clinical responses in over 50% of patients with disease progression on oral antiandrogen.
- GM-CSF, as a potent stimulator of dendritic cells, has demonstrated clinical activity in prostate cancer.
- GM-CSF is well tolerated in patients with prostate cancer. The addition of GM-CSF to antitumor therapy may augment the T cell response to apoptotic tumor cells and therefore may improve the clinical benefit produced by such agents.
- The addition of mitoxantrone with ketoconazole demonstrated improved clinical benefit relative to the published data with each single agent.
The importance of this trial in the broader context of clinical research for prostate cancer is twofold: One, it represents an attempt to offer second line immunotherapy plus chemotherapy to patients who have failed prior frontline taxane based therapy. Two, this is the first trial to assess the combination of GM-CSF plus ketoconazole and mitoxantrone.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Other | Drug: GM-CSF, Drug: Ketoconazole, Drug: MitoxantroneGM-CSF given in combination with ketoconazole and mitoxantrone in patients with progressive prostate cancer despite androgen deprivation and prior taxane containing chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| GM-CSFAlso: LeukineGM-CSF will be administered as a subcutaneous injection at a dose of 250mcg/m2/d (maximum 500 mcg) on weeks 2 and 3 each 21 day cycle (total of 14 days). | Drug | A |
| KetoconazoleAlso: Nizoral, Extina, Xolegel, KuricKetoconazole will be administered daily at a dose of 400 mg po tid (either 1 hour before or 2 hours after meals), ascorbic acid 250 mg po tid (given with ketoconazole) and replacement doses of hydrocortisone (20 mg po in the morning and 10 mg po in the evening). | Drug | A |
| MitoxantroneAlso: Novantrone, MitoxantroneMitoxantrone will be given at dose of 12 mg/m2 every 3 weeks, up to a maximum cumulative dose of 140 mg/m2 | Drug | A |
Primary outcome
To evaluate the effect of the combination of ketoconazole and mitoxantrone plus GM-CSF on time to clinical progression in patients with prostate cancer that has progressed on prior therapy.
Time frame: restaged every 9 weeks
2 secondary outcomes
To evaluate the objective response frequency of the combination of ketoconazole and mitoxantrone plus GM-CSF.
Time frame: restaged every 9 weeks
To investigate the safety of ketoconazole and mitoxantrone given in combination with GM-CSF.
Time frame: AE reporting as occurs
Results and safety
The study was stopped early (reason given: PI decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2016.
- Individual participant dataSharing planned: No
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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.
Robert J Amato, DO principal investigator
Baylor College of Medicine - Methodist Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GM-CSF, Ketoconazole and Mitoxantrone in people with Prostatic Neoplasms, run by The Methodist Hospital Research Institute at 1 site 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?
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: stopped early, as of the sponsor's last update on 17 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study was stopped early (reason given: PI decision). Results are not available in the source record.
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?
To evaluate the effect of the combination of ketoconazole and mitoxantrone plus GM-CSF on time to clinical progression in patients with prostate cancer that has progressed on prior therapy. (time frame: restaged every 9 weeks). 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 17 Mar 2016.