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Trial of GM-CSF Given in Combination With Ketoconazole and Mitoxantrone in Patients With Progressive Prostate Cancer

Phase 2
Terminated
Conditions
Prostatic Neoplasms
Interventions
Registration Number
NCT00447473
Lead Sponsor
The Methodist Hospital Research Institute
Brief Summary

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:

1. Ketoconazole produces serologic and objective clinical responses in over 50% of patients with disease progression on oral antiandrogen.

2. GM-CSF, as a potent stimulator of dendritic cells, has demonstrated clinical activity in prostate cancer.

3. 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.

4. 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.

Recruitment & Eligibility

Status
TERMINATED
Sex
Male
Target Recruitment
31
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AGM-CSFGM-CSF given in combination with ketoconazole and mitoxantrone in patients with progressive prostate cancer despite androgen deprivation and prior taxane containing chemotherapy
AKetoconazoleGM-CSF given in combination with ketoconazole and mitoxantrone in patients with progressive prostate cancer despite androgen deprivation and prior taxane containing chemotherapy
AMitoxantroneGM-CSF given in combination with ketoconazole and mitoxantrone in patients with progressive prostate cancer despite androgen deprivation and prior taxane containing chemotherapy
Primary Outcome Measures
NameTimeMethod
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.restaged every 9 weeks
Secondary Outcome Measures
NameTimeMethod
To evaluate the objective response frequency of the combination of ketoconazole and mitoxantrone plus GM-CSF.restaged every 9 weeks
To investigate the safety of ketoconazole and mitoxantrone given in combination with GM-CSF.AE reporting as occurs

Trial Locations

Locations (1)

Baylor College of Medicine - Methodist Hospital

🇺🇸

Houston, Texas, United States

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