Phase II Trial to Assess the Activity of Ketoconazole and Mitoxantrone Plus GM-CSF in Patients With Progressive Hormone Refractory Prostate Cancer
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
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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
Robert J Amato, DO
The Methodist Hospital Research Institute
United States: Institutional Review Board
|The Methodist Hospital Research Institute||Houston, Texas 77030|