Safety and Efficacy Study of GM-CSF, Thalidomide Plus Docetaxel in Prostate Cancer - Full Text View

Sponsors and Collaborators:	The Methodist Hospital System Bayer
Information provided by:	The Methodist Hospital System
ClinicalTrials.gov Identifier:	NCT00450008

Purpose

The purpose of this study is to assess the relative efficacy and toxicity of combination therapy of GM-CSF, Thalidomide plus Docetaxel in patients with prostate cancer with a rising PSA.

Condition	Intervention	Phase
Prostatic Neoplasms	Drug: GM-CSF Drug: thalidomide Drug: docetaxel	Phase II

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Docetaxel Thalidomide Sargramostim Granulocyte-macrophage colony-stimulating factor Warfarin Warfarin potassium Warfarin sodium

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 Study of Patients With Hormone-Naïve Prostate Cancer With a Rising Prostate Specific Antigen: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Thalidomide Plus Docetaxel

Further study details as provided by The Methodist Hospital System:

Primary Outcome Measures:

To assess the relative efficacy of the combination of GM-CSF, Thalidomide and Docetaxel in patients with prostate cancer.

Secondary Outcome Measures:

Collect data on hormonal responses produced by GM-CSF, Thalidomide and Docetaxel.
Evaluate safety and toxicity of the combination of GM-CSF, Thalidomide and Docetaxel for patients with hormone naïve prostate cancer.

Enrollment:	9
Study Start Date:	December 2006
Estimated Study Completion Date:	September 2008
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A Combination therapy of GM-CSF, Thalidomide plus Docetaxel in patients with prostate cancer with a rising PSA	Drug: GM-CSF fixed dose of 250 mcg/m2, 3 days per week by subcutaneous injection Drug: thalidomide Thalidomide by oral administration at a fixed dose of 200 mg. Prophylactic Coumadin® by oral administration at a fixed dose of 2.5 mg to prevent thromboembolic events (DVT and TIA/stroke) during Thalidomide administration. Thalidomide and Coumadin will be given daily at bedtime without interruption. Drug: docetaxel Docetaxel will be administered by intravenous piggyback over 1 hour at 75mg/m² every 3 weeks. Pre-medication for the docetaxel infusion will consist of dexamethasone 8 mg administered orally 12 hours, 3 hours and 1 hour before docetaxel.

Arms

Assigned Interventions

A

Combination therapy of GM-CSF, Thalidomide plus Docetaxel in patients with prostate cancer with a rising PSA

Drug: GM-CSF

fixed dose of 250 mcg/m2, 3 days per week by subcutaneous injection

Drug: thalidomide

Thalidomide by oral administration at a fixed dose of 200 mg. Prophylactic Coumadin® by oral administration at a fixed dose of 2.5 mg to prevent thromboembolic events (DVT and TIA/stroke) during Thalidomide administration. Thalidomide and Coumadin will be given daily at bedtime without interruption.

Drug: docetaxel

Docetaxel will be administered by intravenous piggyback over 1 hour at 75mg/m² every 3 weeks. Pre-medication for the docetaxel infusion will consist of dexamethasone 8 mg administered orally 12 hours, 3 hours and 1 hour before docetaxel.

Detailed Description:

As more men are being diagnosed and treated for prostate cancer at an early age, the number who experiences a rising level of prostate-specific antigen (PSA) after initial treatment is increasing, affecting approximately 50,000 patients each year.

These three drugs are commercially available. Thalidomide is an angiogenesis inhibitor which blocks the development of new blood vessels. GM-CSF stimulates the body's immune response to fight cancer. Docetaxel is the most active chemotherapeutic agent in the treatment of prostate cancer. GM-CSF and thalidomide have proven activity in suppressing PSA values.

This study design offers an opportunity to add cytotoxic therapy (docetaxel) in combination with an active pathobiologic regimen (GM-CSF plus thalidomide) to eradicate micrometastatic disease, thus potentially offering a significant delay to clinical failure as measured by a rise in PSA or radiographic involvement. Additionally, delays in the use of hormone therapy has the potential to be of significant benefit.

GM-CSF will be administered at a fixed dose 3 days per week by subcutaneous injection for 12 months. Participants will receive a fixed dose of thalidomide orally at bedtime daily without interruption for 12 months. Docetaxel will be administered intravenously over 1 hour on week 1 of every cycle (every 3 weeks) for 18 weeks.

Eligibility

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

Criteria

Inclusion Criteria:

Diagnosis of adenocarcinoma of the prostate.
Failure of local treatments (surgery and/or radiation) as defined by a rising PSA; demonstrated by at least three consecutive rises in PSA by intervals of at least 4 weeks apart with an absolute change of at least 1 ng/mL. If the confirmatory PSA (third PSA) is less than the previous screening PSA value, an additional test for rising PSA will be required to document progression.
No clinical or radiographic evidence of disease.
The Zubrod performance status 0-1.
Prior hormonal therapy in the form of neoadjuvant or adjuvant therapy is allowed as long as androgen therapy has been completed at least 1 year prior to study entry.
Adequate hematologic function: absolute granulocytes ≥ 1500/ul, platelets ≥ 100,000/ul, hemoglobin ≥ 10 gm/100 ml within 4 weeks prior to study entry.
Adequate hepatic function: bilirubin ≤ 1.5 mg/dl, liver enzymes ≤ 1.5 ULN within 4 weeks prior to study entry.
Adequate renal function: creatinine ≤ 1.5 x ULN within 4 weeks prior to study entry.
Patients treated with bisphosphonate therapy before or after study entry are eligible to continue in the study.
Negative bone scan within 6 weeks prior to study entry.
Negative CT scan or MRI of the abdomen and pelvis within 6 weeks prior to study entry.
Negative chest x-ray for metastatic disease within 6 weeks prior to study entry.
Patients must sign a written informed consent prior to treatment.

Exclusion Criteria:

Serious intercurrent medical illness including symptomatic heart disease within 6 months.
Previous or concurrent invasive cancers other than superficial non-melanomatous skin cancer unless disease-free for at least 5 years.
Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow-up.
History of thromboembolic events (deep venous thrombosis, symptomatic cerebrovascular events or pulmonary embolism), history of MI, within the last 12 months.
History of bleeding disorders that would contraindicate Coumadin® (warfarin) including: esophageal varices and clotting factor defects

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00450008

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, DO )
Study ID Numbers:	PCa-06-102, 1006-0153
Study First Received:	March 19, 2007
Last Updated:	August 21, 2008
ClinicalTrials.gov Identifier:	NCT00450008
Health Authority:	United States: Institutional Review Board

Keywords provided by The Methodist Hospital System:

Prostate Cancer
Hormone-Naïve Prostate Cancer
adenocarcinoma of the prostate

Study placed in the following topic categories:

Docetaxel
Dexamethasone
Thalidomide
Prostatic Diseases
Genital Neoplasms, Male
Urogenital Neoplasms

Warfarin
Genital Diseases, Male
Adenocarcinoma
Prostatic Neoplasms
Dexamethasone acetate

Additional relevant MeSH terms:

Anti-Infective Agents
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Immunosuppressive Agents
Angiogenesis Inhibitors
Pharmacologic Actions

Anti-Bacterial Agents
Neoplasms
Neoplasms by Site
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Leprostatic Agents

ClinicalTrials.gov processed this record on January 14, 2009