Clinical trial NCT00479089
Conditions: Bladder Cancer
Keywords: Transitional Cell Carcinoma Urothelium Urothelial Cancer Bladder Cancer Docetaxel Taxotere ZD1839 Gefitinib Iressa Consolidation Therapy
Sponsor: M.D. Anderson Cancer Center
Start date: 2004-02-01; Completion date: 2014-08-01
Enrollment: 50 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Primary Objective:

1\. To compare the proportion of patients free from progression 9 months from the start of consolidation therapy with the combination of docetaxel and ZD1839 (Iressa) versus docetaxel alone. For the purposes of this protocol, "consolidation" therapy refers to treatment given at the time of maximal benefit from conventional front-line multi-agent chemotherapy.

Secondary Objective:

1\. To compare time to progression (TTP), overall survival (OS) and cause-specific survival (CSS) in the two arms. For completeness, these will be reported both from the initiation of consolidation chemotherapy, and from the completion of induction chemotherapy.

Detailed description:
Docetaxel is a drug designed to help stop cancer cells from growing and dividing. ZD1839 is also a drug designed to block cancer cells from growing and dividing.

Before treatment starts, you will have a complete physical exam. Blood (2-3 tablespoons) and urine tests will be taken as part of the usual evaluation of liver, bone marrow, blood clotting ability, and kidney function. A chest x-ray and ECG (test to measure the electrical activity of the heart) will be done. You will have imaging studies such as a CT scan of the chest abdomen and pelvis and a bone scan to show the location of current tumors. If needed, an MRI scan of the brain will be done. This evaluation is considered standard. Women who are able to have children must have a negative blood pregnancy test. Patients who have a history of invasive tumors in their bladder, and who have not had a prior cystoscopy, must have a screening cystoscopy with an EUA (examination under anesthesia), to check the extent of disease in their bladder. An EUA of the bladder is a standard procedure for diagnosing and checking the status of bladder cancer.

You will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in one group will receive docetaxel alone. Participants in the other group will receive docetaxel plus ZD1839. There is an equal chance of being assigned to either group. Both you and the study doctor will know to which group you were assigned.

Docetaxel will be given through a catheter (a plastic tube) placed in a large vein in the chest or arm. The medication will be given over about thirty minutes one day each week for 4 weeks. This will be followed by a 2 week break. The 4 weeks of treatment and 2 weeks without treatment will be considered one course (6 weeks).

Dexamethasone will be given to decrease the risk of having an allergic reaction to the docetaxel. In the first cycle, you will receive 3 doses of dexamethasone by mouth every 12 hours starting the night before the docetaxel infusion. If you have no reaction, the dexamethasone will be decreased in Course 2 to one dose twice on the day of therapy. If there is no reaction in Course 2, the dexamethasone will be decreased further to 1 dose 1 hour before docetaxel treatment.

ZD1839 is a medication taken by mouth every day without break. Participants in the docetaxel plus ZD1839 group will take one ZD1839 tablet once a day at about the same time. You can take ZD1839 with or without food. If you forget to take a dose, take the last missed dose as soon as you remember, as long as it is at least 12 hours before the next dose is due. If it is less than 12 hours until the next dose, do not take the dose you have missed.

During treatment, you will have a weekly blood test (2-3 tablespoons) to measure bone marrow function. A physical exam and blood tests (2-3 tablespoons) will be repeated before each cycle of treatment. Imaging studies will be repeated at 9 months but may be performed sooner if you have symptoms that show your tumor may be getting worse. These scans are considered part of standard routine follow-up.

You will be on study as long as the tumor is not growing at a certain rate and there are no severe side effects. Therapy will be stopped and you may be taken off study early if one or both of these things occur. After 6 months, patients can choose to continue therapy if they wish. At the end of 4 cycles, you will have the option to continue your assigned therapy as long as it is tolerated and there is no evidence that the disease is getting worse. There is no maximum amount of time that you can receive treatment on this study.

After the study is complete, follow-up will be arranged at the discretion of your treating physician.

This is an investigational study. The FDA has authorized ZD1839 for research use only. A total of 90 patients may take part in this study. All will be enrolled at M. D. Anderson.

Arms: arm 1: Docetaxel 25 mg/m\^2 IV over 30 minutes for 4 weeks with premedication with Dexamethasone, followed by 2 weeks off therapy. arm 2: Docetaxel 25 mg/m\^2 IV over 30 minutes for 4 weeks with premedication with Dexamethasone, followed by 2 weeks off therapy. ZD1839 250 mg by mouth daily, without break.
Interventions: intervention 1: Docetaxel intervention 2: ZD1839 intervention 3: Dexamethasone
Intervention descriptions: intervention 1: 25 mg/m2 IV over 30 minutes for 4 weeks, followed by 2 weeks off therapy. intervention 2: 250 mg by mouth daily, without break. intervention 3: Course #1: 3 doses of prophylactic Dexamethasone 4mg orally every 12 hours, starting the night before the Docetaxel infusion.

Course #2: If no hypersensitivity reactions and no significant fluid retention during course 1, the Dexamethasone is reduced to 4mg orally twice daily on the day of therapy.

Course #3 and subsequent courses: If no hypersensitivity reactions and no significant fluid retention during course 2, the Dexamethasone is reduced to 4mg orally one hour before treatment.

Protocol documents: