Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Docetaxel

Vaccines

Tubulin Modulators

Antimitotic Agents

Patients randomized to Arm 1 will receive treatment cycles of Docetaxel and vaccine.

PI relocated, data not available.

Patients randomized to Arm 2 will receive Docetaxel 75 mg/m2 on Day 1 of each cycle (1 cycle = 3 weeks). Patients who demonstrate disease progression will continue with their chemo as scheduled in Arm 2 but will also begin to receive TroVax® (cross-over).

PI relocated, data not available.

Docetaxel will be administered at the completion of the first three TroVax® injections. Patients will receive Docetaxel 75 mg/m2 on Day 1 of each cycle (1 cycle = 3 weeks). Patients will receive up to 10 total Docetaxel infusions over the course of the study. Subsequent TroVax® injections will be delivered on Day 1 of each Docetaxel cycle, 2 hours prior to the chemotherapy administration.

MVA 5T4

Patients will receive Docetaxel 75 mg/m2 on Day 1 of each cycle (1 cycle = 3 weeks). Patients who demonstrate disease progression will continue with their chemo as scheduled in Arm 2 but will also begin to receive TroVax® (cross-over). Patients will receive up to 10 total Docetaxel infusions over the course of the study. If patients cross-over, TroVax® will be administered 2 hours prior to the chemotherapy administration.

Robert J Amato, DO

The purpose of this study is to evaluate the role of combination therapy with Trovax plus Docetaxel or Docetaxel alone in patients with prostate cancer with a rising prostate specific antigen (PSA).

Docetaxel is the most active chemotherapeutic agent in the treatment of prostate cancer.

Trovax is vaccine that targets 5T4 receptors on tumor cells. 5T4 has been detected in the majority of primary prostate cancers. Based on pre-clinical and clinical data, it may be advantageous to administer a cancer vaccine before chemotherapy to enhance immune responses, thus leading to a more therapeutic approach for patients with metastatic androgen independent prostate cancer (AIPC).

Study of Trovax® Plus Docetaxel Versus Docetaxel Alone in Patients With Progressive Hormone Refractory Prostate Cancer

A Phase II Trial to Assess the Activity of MVA 5T4 (Trovax®) Plus Docetaxel Versus Docetaxel Alone in Patients With Progressive Hormone Refractory Prostate Cancer (HRPC)

Oxford BioMedica

The Methodist Hospital Research Institute

Micronutrients

Anti-Inflammatory Agents

Analgesics

Anti-Infective Agents

Vitamins

Ascorbic Acid

Androgens

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Mitoxantrone

Sargramostim

Taxane

Ketoconazole

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Cytochrome P-450 Enzyme Inhibitors

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Vitamin C

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).

GM-CSF

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).

Mitoxantrone will be given at dose of 12 mg/m2 every 3 weeks, up to a maximum cumulative dose of 140 mg/m2

This trial represents an attempt to offer second line immunotherapy plus chemotherapy to patients who have failed prior taxane base therapy.

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.

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

Bayer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Trovax® Plus Docetaxel Versus Docetaxel Alone in Patients With Progressive Hormone Refractory Prostate Cancer	NCT00521274	Prostatic Neopl...	MVA 5T4 Docetaxel	18 Years -	The Methodist Hospital Research Institute
Trial of GM-CSF Given in Combination With Ketoconazole and Mitoxantrone in Patients With Progressive Prostate Cancer	NCT00447473	Prostatic Neopl...	GM-CSF Ketoconazole Mitoxantrone	18 Years -	The Methodist Hospital Research Institute

Spots Global Cancer Trial Database for progressive hormone refractory prostate cancer