Trial of GM-CSF Given in Combination With Ketoconazole and Mitoxantrone in Patients With Progressive Prostate Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial to Assess the Activity of Ketoconazole and Mitoxantrone Plus GM-CSF in Patients With Progressive Hormone Refractory Prostate Cancer|
- 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 ] [ Designated as safety issue: No ]
- To evaluate the objective response frequency of the combination of ketoconazole and mitoxantrone plus GM-CSF. [ Time Frame: restaged every 9 weeks ] [ Designated as safety issue: No ]
- To investigate the safety of ketoconazole and mitoxantrone given in combination with GM-CSF. [ Time Frame: AE reporting as occurs ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2006|
|Study Completion Date:||September 2008|
|Primary Completion Date:||August 2008 (Final data collection date for primary outcome measure)|
GM-CSF given in combination with ketoconazole and mitoxantrone in patients with progressive prostate cancer despite androgen deprivation and prior taxane containing chemotherapy
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).
Other Name: LeukineDrug: Ketoconazole
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).
Other Name: Nizoral, Extina, Xolegel, KuricDrug: Mitoxantrone
Mitoxantrone will be given at dose of 12 mg/m2 every 3 weeks, up to a maximum cumulative dose of 140 mg/m2
Other Name: Novantrone, Mitoxantrone
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00447473
|United States, Texas|
|Baylor College of Medicine - Methodist Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Robert J Amato, DO||Baylor College of Medicine - Methodist Hospital|