NCT00447473

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

Phase II Trial to Assess the Activity of Ketoconazole and Mitoxantrone Plus GM-CSF in Patients With Progressive Hormone Refractory Prostate Cancer

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: The Methodist Hospital Research Institute · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Prostatic Neoplasms

Interventions

Type	Name	Description
DRUG	GM-CSF	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).
DRUG	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).
DRUG	Mitoxantrone	Mitoxantrone will be given at dose of 12 mg/m2 every 3 weeks, up to a maximum cumulative dose of 140 mg/m2

Timeline

• Start date: 2006-07-01
• Primary completion: 2008-08-01
• Completion: 2008-09-01
• First posted: 2007-03-14
• Last updated: 2016-03-17

Locations

1 site across 1 country: United States