GM-CSF and Thalidomide in Treating Patients Undergoing Surgery for High-Risk Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop tumor cells from growing. Thalidomide may stop the growth of prostate cancer by blocking blood flow to the tumor. Giving GM-CSF and thalidomide before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well giving GM-CSF together with thalidomide works in treating patients undergoing surgery for high-risk prostate cancer.

Detailed Description
-----------------
OBJECTIVES: Evaluate the impact of neoadjuvant sargramostim (GM-CSF) and thalidomide on pathologic response (histologic P0, margin positivity, capsular penetration), prostate-specific antigen (PSA) response, and other investigational endpoints in patients with high-risk prostate cancer undergoing prostatectomy. Determine the safety and feasibility of GM-CSF and thalidomide. OUTLINE: This is an open-label study. Patients receive sargramostim (GM-CSF) subcutaneously on days 1, 3, and 5 and oral thalidomide on days 1-5 or 1-7 in weeks 1-4. Treatment repeats every 4 weeks for 2 courses in the absence of unacceptable toxicity. Patients undergo radical prostatectomy with bilateral pelvic lymphadenectomy at week 8 or 9. PROJECTED ACCRUAL: A total of 29 patients will be accrued for this study.

Official Title
-----------------
Phase II Trial of Neoadjuvant GM-CSF + Thalidomide in High-Risk Patients With Prostate Cancer Undergoing Prostatectomy

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Biological: sargramostim
* Drug: thalidomide
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate meeting any of the following criteria for high-risk disease: Clinical stage II or III (T2b, T2c, or T3 with any grade or prostate-specific antigen [PSA]) Gleason score 7 (4+3 only) or ≥ 8 (any stage or PSA) Serum PSA ≥ 10 ng/dL (any grade or stage) Any stage, PSA, or Gleason score with ≥ 35% chance of biochemical failure at 5 years based on Kattan's nomogram No clinical evidence of CNS metastases No metastatic disease as demonstrated by radiological exam (CT scan, MRI, bone scan, x-ray) within 8 weeks of study entry Appropriate medical candidate for radical prostatectomy PATIENT CHARACTERISTICS: ECOG performance status 0-1 Creatinine ≤ 2.0 mg/dL Granulocyte count ≥ 1,800/mm³ Platelet count ≥ 100,000/mm³ AST < 3 times upper limit of normal Bilirubin ≤ 1.5 mg/dL Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment No active unresolved infection No pre-existing peripheral neuropathy > grade 1 No known HIV positivity No other malignancy within the past 5 years except curatively treated basal cell or squamous cell carcinoma of the skin or controlled Ta transitional cell carcinoma of the bladder No known contraindication to sargramostim (GM-CSF) or thalidomide PRIOR CONCURRENT THERAPY: No prior radiotherapy to the prostate or pelvis No prior chemotherapy or hormonal therapy for prostate cancer No parenteral antibiotics within the past 7 days

Ages Eligible for Study
-----------------
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GM-CSF Injections and Oral Thalidomide<br>taught to administer an injection of GM-CSF under your skin (subcutaneous injection) and will administer this medicine to yourself every Monday, Wednesday and Friday for 4 weeks at time. Thalidomide will be taken orally (by mouth) every evening at bed time. You will continue these injections 3 times a week and the daily oral medicine for up to 2 months if the therapy appears to be helping your disease. | Biological: sargramostim<br>* administered subcutaneously, generally well tolerated doses range from 50-500 ug/m2/day<br>* Other names: GM-CSF;Drug: thalidomide<br>* doses up to 400 mg/day<br>* Other names: THALOMID;Procedure: conventional surgery<br>* SOC care surgery<br>Procedure: neoadjuvant therapy<br>* post radical prostatectomy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients P0 at Surgery | Pathologic Complete Response is defined as complete eradication of tumor. | 8 weeks | 
| Proportion of Patients With Negative Surgical Margins | Presence or Absence of prostate cancer tissue at the sites of surgical resection. This is done by reviewing the entire specimen resected at the time or Radical Prostatectomy. | 8 Weeks | 
| Prostate-specific Antigen Response | Number of subjects that achieved a PSA decline while on therapy. Any PSA decline while on treatment, compared with baseline PSA prior to study entry. | 8 weeks | 
| Time to Clinical Progression | Time to progression. WIth a median follow up of 32 months (12-51 months), 5 of 26 patients developed biochemical failure. | 32 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage III prostate cancer, stage II prostate cancer, adenocarcinoma of the prostate, stage I prostate cancer, stage IV prostate cancer