Pemetrexed Disodium and Gemcitabine in Treating Patients With Advanced Cancer of the Urothelium

Study Overview
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Brief Summary
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RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining pemetrexed disodium with gemcitabine may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining pemetrexed disodium with gemcitabine in treating patients who have advanced cancer of the urothelium.

Detailed Description
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OBJECTIVES: Primary Determine the response rate in patients with previously untreated advanced cancer of the urothelium treated with pemetrexed disodium and gemcitabine. Determine the toxicity of this regimen in these patients. Secondary Determine the overall survival and time to progression in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive pemetrexed disodium IV over 10 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Patients also receive cyanocobalamin intramuscularly once every 9 weeks and folic acid orally once daily beginning on day -6 and continuing until 3 weeks after the completion of study therapy. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 24-46 patients will be accrued for this study within 15 -18 months.

Official Title
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Phase II Trial Of Pemetrexed Disodium And Gemcitabine In Advanced Urothelial Cancer

Conditions
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Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Urethral Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: pemetrexed disodium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed cancer of the urothelium (renal pelvis, ureter, bladder, or urethra) Any of the following types: Transitional cell carcinoma (TCC) Mixed histologies containing a component of TCC Non-TCC of the urothelium (renal pelvis, ureter, bladder, or urethra) Progressing regional or metastatic disease Measurable disease No clinical evidence of CNS metastases No evidence of clinically significant (by physical exam or plain film) third-space fluid collections (pleural effusions or ascites) PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL Hepatic AST no greater than 3 times upper limit of normal (ULN) Bilirubin no greater than 1.5 times ULN Renal Creatinine clearance at least 45 mL/min Cardiovascular No history of severe cardiovascular disease (i.e., American Heart Association class III or IV heart disease) No uncontrolled congestive heart failure No ventricular dysrhythmias Other Not pregnant or nursing Fertile patients must use effective contraception No active unresolved infection No other prior malignancy unless curatively treated and disease free for an appropriate (disease-specific) period of time Able and willing to receive folic acid and cyanocobalamin supplementation PRIOR CONCURRENT THERAPY: Biologic therapy No prior systemic biologic response modifier therapy Chemotherapy No prior systemic chemotherapy for metastatic disease More than 1 year since prior neoadjuvant or adjuvant chemotherapy Endocrine therapy Not specified Radiotherapy At least 4 weeks since prior radiotherapy and recovered No prior pelvic radiotherapy No concurrent radiotherapy Surgery At least 4 weeks since prior major surgery and recovered Other More than 7 days since prior parenteral antibiotics No salicylates for 2 days before, during, and for 2 days after administration of pemetrexed disodium No nonsteroidal anti-inflammatory drugs for at least 5 days before, during, and for 2 days after administration of pemetrexed disodium

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed Disodium and Gemcitabine<br>Pemetrexed disodium 500 mg/m2 followed by gemcitabine 1000 mg/m2 on day 1 and gemcitabine 1000 mg/m2 on day 8 of a 21-day cycle for a maximum of 6 cycles | Drug: gemcitabine hydrochloride<br> <br> Drug: pemetrexed disodium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response as measured by RECIST criteria |  | Assessed every 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease progression |  | Assessed every 6 weeks | 
| Overall survival |  | Assessed every 3 months for 2 years, then every 6 months for 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic transitional cell cancer of the renal pelvis and ureter, recurrent transitional cell cancer of the renal pelvis and ureter, regional transitional cell cancer of the renal pelvis and ureter, transitional cell carcinoma of the bladder, recurrent bladder cancer, stage III bladder cancer, stage IV bladder cancer, anterior urethral cancer, posterior urethral cancer, recurrent urethral cancer, urethral cancer associated with invasive bladder cancer