"THE p53 TRIAL"
MVAC in Organ- Confined Bladder Cancer Based on p53 Status

This is an important study designed to provide better understanding of bladder cancer and how to treat patients with this disease. This trial is funded by the National Cancer Institute, and will enroll more than 500 patients in about three years from over 30 hospitals around the world.

Background information: Like all tumors, the development of bladder cancer occurs through various mechanisms, which usually involve a change in one of your genes. Genes are like blueprints for our bodies. They contain information that determines our appearance and many aspects of our health. Chromosomes are the packages of genes found in our cells. Like all cancers, bladder cancer develops when alterations of the genes accumulate over time. The most common gene alteration found in tumors occurs in a gene called "p53". The p53 gene is located on chromosome number 17 (see figure 1). The normal function of the p53 gene is to prevent the development of tumor growth, and that is why when the p53 gene is altered, the chance of developing a tumor increases.

Figure 1. Each human cell contains 23 pairs of chromosomes which can be distinguished by size and by unique banding patterns. The p53 tumor suppressor gene is located on chromosome number 17. (National Institutes of Health)

An abnormality of the p53 gene occurs in about 40% of patients with bladder cancer that has invaded into the bladder wall. Some studies suggest that those bladder tumors with an abnormal p53 (also called p53 altered or p53+) may be slightly more aggressive and therefore pose a greater risk for tumor recurrence after removal of the bladder.

Figure 2.Cross-section of the bladder wall. The stages of tumors which will be evaluated in this study are the P1, P2a, and P2b tumors. (Cancer Research 37: 2838-2842, 1977).

Purpose of the "p53 Trial": This study aims to determine whether patients with tumors containing a normal p53 gene live longer than patients with tumors containing an abnormal p53 gene. It will also demonstrate whether chemotherapy can improve the survival of patients with tumors containing an abnormal p53 gene.

To get involved in the study: Individuals who meet certain requirements will be invited to participate in this study. Once you have completed surgery with total removal of bladder and tumor (cystectomy), your physician will determine if your bladder tumor is limited within the wall of the bladder (organ-confined), and has not spread through the wall or to any other part of your body (see figure 2). Once it is determined that you are eligible for the trial, you may sign up (register) for the trial. This will occur within 9 weeks following your surgery.

Once you have signed up (registered) for the p53-trial: (see figure 3). Upon registration, your bladder tumor will be studied to determine if there is an alteration in the p53 gene. To do this, a sample of your tumor (removed at cystectomy) will be sent to a laboratory at the University of Southern California (USC) for special genetic analysis. This information will be kept confidential by the investigators and the research committee. Specific study related information will be made available to the National Cancer Institute, the Food and Drug Administration, USC, and the hospital where you are treated. If the results of this study are published in medical literature, you will be identified by name.
If your bladder tumor contains a normal p53 you will not receive any additional therapy, and you will be observed with a standard follow-up schedule. Currently, close follow-up after surgery is the standard-of-care for individuals with organ-confined bladder cancer.

If your bladder tumor has an abnormal p53, you will then be selected to receive either some additional therapy (chemotherapy), or monitored with standard follow-up. We will use a computer program to determine whether you will be selected for standard follow-up or to receive chemotherapy. This process is called randomization.

The randomization process: If your bladder tumor is found to have an abnormal p53 gene, and you have decided to become involved in the study, you will then be randomized. This will occur within 10 weeks following your surgery.

Randomization is a procedure similar to flipping a coin. You will be selected for one of two options. This selection is not determined by your physician. The decision is made by a computer. The options will be either standard follow-up or some additional treatment (chemotherapy). Your chances of being selected for either of the two treatment options are equal.

The timing and dosage of chemotherapy: If you are randomized to receive chemotherapy, this will begin within 12 weeks following your surgery. This will allow ample time to heal from your operation prior to beginning the chemotherapy.

You will receive a total of 3 ''cycles" of chemotherapy. This will include about 12 days of chemotherapy over the course of 3 months. The chemotherapy will be administered by your medical oncologist though a vein as an outpatient, or possibly as an inpatient. You will be monitored and followed closely during and after your treatment.

Standard follow-up: If you are selected for standard follow-up, you will be monitored carefully. Currently, observation (no additional treatment) is the accepted standard-of-care for patients with this type of bladder cancer following surgery.

However, if your tumor returns (recurs), you will be provided with the best available treatment at that time.

The results of this trial will be important in the future treatment of patients and the better understanding of bladder cancer. Furthermore, we would like to express that both chemotherapy and standard follow-up are very acceptable forms of therapy.