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

Sponsors and Collaborators:	The Methodist Hospital System Bayer
Information provided by:	The Methodist Hospital System
ClinicalTrials.gov Identifier:	NCT00447473

Purpose

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 II

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Hydrocortisone Cortisol 21-phosphate Cortisol succinate Hydrocortamate Hydrocortisone 21-sodium succinate Hydrocortisone acetate Hydrocortisone cypionate Hydrocortisone hemisuccinate Proctofoam-HC Mitoxantrone hydrochloride Mitoxantrone Sargramostim Granulocyte-macrophage colony-stimulating factor Ketoconazole Ascorbic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase II Trial to Assess the Activity of Ketoconazole and Mitoxantrone Plus GM-CSF in Patients With Progressive Hormone Refractory Prostate Cancer

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 ] [ Designated as safety issue: No ]

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 ] [ 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 ]

Enrollment:	31
Study Start Date:	July 2006
Estimated Study Completion Date:	September 2008
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A 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). 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

Arms

Assigned Interventions

A

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).

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

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:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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%.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00447473

Locations

United States, Texas
The Methodist Hospital Research Institute
Houston, Texas, United States, 77030

Sponsors and Collaborators

The Methodist Hospital System

Bayer

Investigators

Principal Investigator:

Robert J Amato, DO

The Methodist Hospital Research Institute

More Information

Responsible Party:	The Methodist Hospital Research Institute ( Robert J. Amato, D.O. )
Study ID Numbers:	PC-Keto-Mito.2006, 0106-0010
Study First Received:	March 12, 2007
Last Updated:	August 21, 2008
ClinicalTrials.gov Identifier:	NCT00447473
Health Authority:	United States: Institutional Review Board

Keywords provided by The Methodist Hospital System:

Prostate Cancer
progressive hormone refractory prostate cancer

Study placed in the following topic categories:

Hydrocortisone
Genital Neoplasms, Male
Prostatic Diseases
Cortisol succinate
Clotrimazole
Miconazole
Tioconazole

Urogenital Neoplasms
Genital Diseases, Male
Ketoconazole
Hydrocortisone acetate
Mitoxantrone
Prostatic Neoplasms
Ascorbic Acid

Additional relevant MeSH terms:

Anti-Infective Agents
Neoplasms
Neoplasms by Site
Sensory System Agents
Antineoplastic Agents
Therapeutic Uses

Antifungal Agents
Physiological Effects of Drugs
Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009