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

This study has been terminated.
(PI decision)
Information provided by (Responsible Party):
The Methodist Hospital System Identifier:
First received: March 12, 2007
Last updated: March 15, 2016
Last verified: March 2016
This trial represents an attempt to offer second line immunotherapy plus chemotherapy to patients who have failed prior taxane base therapy.

Condition Intervention Phase
Prostatic Neoplasms
Drug: GM-CSF
Drug: Ketoconazole
Drug: Mitoxantrone
Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:

Further study details as provided by The Methodist Hospital System:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 31
Study Start Date: July 2006
Study Completion Date: September 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
GM-CSF given in combination with ketoconazole and mitoxantrone in patients with progressive prostate cancer despite androgen deprivation and prior taxane containing chemotherapy
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).
Other Name: Leukine
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).
Other Name: Nizoral, Extina, Xolegel, Kuric
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
Other Name: Novantrone, Mitoxantrone

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
  • 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%.
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Please refer to this study by its identifier: NCT00447473

United States, Texas
Baylor College of Medicine - Methodist Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
The Methodist Hospital System
Principal Investigator: Robert J Amato, DO Baylor College of Medicine - Methodist Hospital
  More Information

Responsible Party: The Methodist Hospital System Identifier: NCT00447473     History of Changes
Other Study ID Numbers: HMRI IRB#0106-0010
PC-Keto-Mito.2006 ( Other Identifier: Principal Investigator )
Study First Received: March 12, 2007
Last Updated: March 15, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by The Methodist Hospital System:
Prostate Cancer
progressive hormone refractory prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Cytochrome P-450 CYP3A Inhibitors processed this record on April 28, 2017