S0028, Gemcitabine and Paclitaxel in Treating Patients With Advanced or Recurrent Cancer of the Urinary Tract

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining gemcitabine and paclitaxel in treating patients who have advanced or recurrent cancer of the urinary tract.

Detailed Description
-----------------
OBJECTIVES: Determine the feasibility of enrolling patients aged 70 years and older with advanced or recurrent urothelial cancer to a structured phase II study. Determine the anticancer efficacy of gemcitabine and paclitaxel, in terms of objective response rate and 2-year survival, in these elderly patients. Assess the toxicity and tolerability of this regimen in these elderly patients. Determine the feasibility of using standardized self-report measures of comorbidity, depression, and functional status in these patients. Determine the pharmacokinetics of this regimen in these elderly patients and validate this data against similar parameters in patients aged under 60 years. OUTLINE: This is a multicenter study. Patients are stratified according to age (70 and over vs under 60). Patients receive paclitaxel IV over 3 hours on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline. Patients are followed every 3 months for 1 year and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 80 patients (60 age 70 and over and 20 under age 60) will be accrued for this study.

Official Title
-----------------
Protocol for Assessment of Gemcitabine and Paclitaxel for Metastatic Urothelial Cancer in Patients Aged 70 Years or Older (and in a Cohort of Patients Younger Than 60 Years)

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

Intervention / Treatment
-----------------
* Drug: gemcitabine hydrochloride
* Drug: paclitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed urothelial cancer Transitional cell carcinoma, adenocarcinoma, or squamous carcinoma (bladder, renal pelvis, ureter, or urethra) Previously untreated metastatic or locoregionally advanced (i.e., bulky pelvic nodes) disease OR Locally recurrent carcinoma after radiotherapy or cystectomy and no longer eligible for further radiotherapy or surgery Measurable disease PATIENT CHARACTERISTICS: Age: 70 and over OR Under 60 Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: Absolute granulocyte count at least 1,200/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than upper limit of normal (ULN) Aspartate aminotransferase (SGOT) or alanine aminotransferase (SGPT) no greater than 2 times ULN Renal: Creatinine no greater than ULN Other: HIV negative No other concurrent life-threatening medical disorder that would preclude study participation No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Prior adjuvant chemotherapy is allowed provided administered more than 10 years ago No prior gemcitabine, taxanes, or platinum-based adjuvant chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 28 days since prior radiotherapy and recovered Surgery: See Disease Characteristics At least 28 days since prior surgery and recovered

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

Sexes Eligible for Study
-----------------
All

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: gemcitabine, paclitaxel<br> | Drug: gemcitabine hydrochloride<br> <br> Drug: paclitaxel<br> <br> * Other names: Taxol;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Feasibility of Accruing Patients With Metastatic Bladder Cancer Who Are 70 and Older to Chemotherapy Protocols | Sixty patients aged 70 years and older were to be accrued to the study. The feasibility of accrual was determined that accrual of 3 patients per month in the age 70 and older range would allow for an expeditiously conducted phase II trial. If, after a 3 month start-up period, 3 or more patients aged 70 years and older were accrued per month for the duration of the trial, it was deemed reasonable to consider further trials in this elderly population. | 66 months (protocol activated on 7/1/2001 and closed to accrual on 12/15/2006) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Confirmed Response Rate in the Patients Age 70 and Older (Complete and Partial Response) | Complete response (CR) is defined as complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Partial response (PR) applies only to patients with least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. | every week for the first 4 weeks and then every 3 weeks for up to 19 weeks | 
| Progression-free Survival in Patients Aged 70 Years and Older | Measured form date of registration to date of first observation of progression disease, death due to any cause, symptomatic deterioration, or early discontinuation of treatment. | 0-5 years | 
| Overall Survival (OS) in Patients Aged 70 Years and Older | Measured from date of registration to date of death due to any cause. | 0-5 years | 
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. | Patients were assessed for adverse events weekly after protocol treatment for cycle 1 (1 cycle = 21 days) and then weekly for the first 2 weeks of protocol treatment for cycle 2-6 and after completion of protocol treatment. | 
| Feasibility of Patient-reported Outcome Measures for Patients Aged 70 Years and Older: Form Submission Rate | Patients were required to complete three self-administered questionnaires at entry, prior to the administration of any cytotoxic therapy: the Medical Conditions Questionnaire, Instrumental Activities of Daily Living Form that evaluates functional status, and the Feelings Questionnaire that evaluates depression status. Feasibility is defined in four ways: 1) submission rates for each of three patient self-administered questionnaires (> 60%); 2) the number of items missing within each scale (< 5%); 3) a description of the level of assistance required for self-administration of the questionnaires; and 4) the average amount of time it takes patients to complete each of the three questionnaires. Level of assistance is defined as the need to 1) read the questionnaire to the patient, 2) explain the meaning of items, 3) explain the response format, and 4) complete the questionnaire for the patient; an other category of assistance will be included. | at study entry (prior to administration of any treatment) | 
| Feasibility of Patient-reported Outcome Measures for Patients Aged 70 Years and Older: Median Time of Complete Forms | Patients were required to complete three self-administered questionnaires at entry, prior to the administration of any cytotoxic therapy: the Medical Conditions Questionnaire, Instrumental Activities of Daily Living Form that evaluates functional status, and the Feelings Questionnaire that evaluates depression status. Feasibility is defined in four ways: 1) submission rates for the each of three patient self-administered questionnaires (> 60%); 2) the number of items missing within each scale (< 5%); 3) a description of the level of assistance required for self-administration of the questionnaires; and 4) the average amount of time it takes patients to complete each of the three questionnaires. Level of assistance is defined as the need to 1) read the questionnaire to the patient, 2) explain the meaning of items, 3) explain the response format, and 4) complete the questionnaire for the patient; an other category of assistance will be included. | at study entry (prior to administration of any treatment) | 
| Assess the Feasibility of Patient-reported Outcome Measures for Patients Aged 70 Years and Older: at Least One Type of Assistance Required | Patients were required to complete three self-administered questionnaires at entry, prior to the administration of any cytotoxic therapy: the Medical Conditions Questionnaire, Instrumental Activities of Daily Living Form that evaluates functional status, and the Feelings Questionnaire that evaluates depression status. Feasibility is defined in four ways: 1) submission rates for the three patient self-administered questionnaires (> 60%); 2) the number of items missing within each scale (< 5%); 3) a description of the level of assistance required for self-administration of the questionnaires; and 4) the average amount of time it takes patients to complete each of the three questionnaires. Level of assistance is defined as the need to 1) read the questionnaire to the patient, 2) explain the meaning of items, 3) explain the response format, and 4) complete the questionnaire for the patient; an other category of assistance will be included. | at study entry (prior to administration of any treatment) | 

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