Transrectal Tumour Oxygen - US Army

Study Overview
=================
Brief Summary
-----------------
Prostate cancer is now the most commonly diagnosed tumor among men in the United States. Most patients have tumors that are confined to the prostate gland at diagnosis and are suitable for treatment with surgery or radiotherapy (RT) that is aimed at curing the disease. Nevertheless, despite recent improvements in these treatments, a large number of men continue to die of prostate cancer. These patients often have spread of tumor to other areas of the body, and are treated with hormones that produce initial tumor shrinkage. However, over time the tumor learns to grow despite continued hormonal treatment. Effective therapy for patients with hormone-resistant prostate cancer is lacking and patients often deteriorate quickly and die. Thus, there is a need for better treatment that cures prostate cancer at an early stage, and a better understanding of the biology of prostate cancer specifically with respect to factors that determine the effectiveness of RT, the spread of tumor and the development of hormone-resistant disease. Low levels of oxygen (hypoxia) are known to exist in many human tumors, and studies have shown that hypoxic tumors are less likely to be cured by RT. In addition, hypoxia may lead to lower cure rates following surgery, spread of cancer to other areas of the body, and changes in the genetic characteristics of the cancer cells that cause them to behave more aggressively. The importance of hypoxia in prostate cancer has not previously been evaluated. The aims of this study are to determine how often hypoxia occurs in early prostate cancer and whether hypoxia influences the success of RT, tumor spread beyond the prostate to bones and other organs and the development of hormone-resistant disease. Patients will have tumor oxygen levels measured using a special fine-needle electrode system prior to beginning treatment with either RT or the combination of hormones plus RT. The measurements will be made through the rectum using ultrasound to position and guide the electrode. A biopsy of the tumor will be obtained at the site of the measurements, and this will be used to determine how oxygen influences changes in the genetic character of prostate cancer cells. A total of 195 patients will be evaluated in this way over 3 years. This study will provide unique information about the behavior of prostate cancer, which may help explain why currently available treatments including surgery, RT and hormones fail to cure patients. Assuming that this study shows hypoxia to be important in prostate cancer, future work will focus on new anti-hypoxia treatments to be used in combination with surgery or RT with the aim of overcoming this obstacle and improving cure rates.

Official Title
-----------------
A Study of Transrectal Tumour Oxygen Measurements in Patients With Clinically Localized Prostate Cancer

Conditions
-----------------
Prostatic Neoplasms

Intervention / Treatment
-----------------
* Procedure: Pre-treatment tumour oxygen measurements


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A histologic diagnosis of adenocarcinoma of the prostate A decision to treat using high-dose conformal radiotherapy, with or without neoadjuvant and concurrent androgen ablation Clinical stage T2a or T2b, N0, M0 (UICC 1997 68) No hormonal or cytotoxic anti-cancer therapy prior to study entry ECOG performance status of 2 or less Ability to understand the English language Signed informed consent Exclusion Criteria: Patients with prior or active malignancy within 5 years of the diagnosis of prostate cancer, except non-melanoma skin cancer

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hypoxia and RT in prostate cancer<br> | Procedure: Pre-treatment tumour oxygen measurements<br>* Pre-treatment tumour oxygen measurements<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the relationship between pre-treatment prostate cancer oxygen levels and long-term disease control following treatment with radiotherapy, and the independent prognostic effect of oxygen measurements. |  | after follow-up is completed | 
| To determine the relationship between pre-treatment tumor oxygen levels and mutations of the p53 gene, and the impact of this interaction on patient outcome. |  | after follow up is completed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate oxygen levels in clinically localized prostate cancer prior to treatment. |  | after follow-up is completed | 
| To determine the relationship between pre-treatment tumor oxygen levels and the subsequent development of metastases and androgen-resistant prostate cancer. |  | after follow is completed | 
| To determine whether androgen ablation overcomes any adverse effect of hypoxia on outcome. |  | after follow up is completed |