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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Bladder Cancer; Transitional Cell Cancer of the Renal Pelvis and Ureter; Urethral Cancer
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: paclitaxel

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.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90089-9181
      • USC/Norris Comprehensive Cancer Center and Hospital
  • Georgia
    • Valdosta, Georgia, United States, 31603
      • Pearlman Comprehensive Cancer Center at South Georgia Medical Center
  • Illinois
    • Springfield, Illinois, United States, 62781-0001
      • Regional Cancer Center at Memorial Medical Center
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Kansas City, Kansas, United States, 66160-7357
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - Salina
    • Salina, Kansas, United States, 67401
      • Tammy Walker Cancer Center at Salina Regional Health Center
    • Topeka, Kansas, United States, 66606
      • St. Francis Comprehensive Cancer Center
    • Topeka, Kansas, United States, 66604
      • Stormont-Vail Cancer Center
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67203
      • Associates in Womens Health, PA - North Review
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0942
      • University of Michigan Comprehensive Cancer Center
    • Battle Creek, Michigan, United States, 49017
      • Battle Creek Health System Cancer Care Center
    • Bay City, Michigan, United States, 48708
      • Bay Regional Medical Center
    • Big Rapids, Michigan, United States, 49307
      • Mecosta County Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Grand Rapids, Michigan, United States, 49503
      • Lacks Cancer Center at Saint Mary's Health Care
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Hospital - Butterworth Campus
    • Grand Rapids, Michigan, United States, 49506
      • Metropolitan Hospital
    • Holland, Michigan, United States, 49423
      • Holland Community Hospital
    • Muskegon, Michigan, United States, 49443
      • Hackley Hospital
    • Port Huron, Michigan, United States, 48060
      • Mercy Regional Cancer Center at Mercy Hospital
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare
    • Billings, Montana, United States, 59107-7000
      • Deaconess Billings Clinic - Downtown
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Butte, Montana, United States, 59701
      • St. James Community Hospital
    • Great Falls, Montana, United States, 59405
      • Big Sky Oncology
    • Great Falls, Montana, United States, 59405
      • Sletten Regional Cancer Institute at Benefis Healthcare
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology
    • Missoula, Montana, United States, 59801
      • Community Medical Center
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
    • Missoula, Montana, United States, 59804
      • Clinic of Dr. Judy L. Schmidt
  • Nebraska
    • Kearney, Nebraska, United States, 68848-1990
      • Good Samaritan Cancer Center at Good Samaritan Hospital
  • New York
    • Clifton Springs, New York, United States, 14432
      • Finger Lakes Hematology and Oncology
    • Middletown, New York, United States, 10940-4199
      • Tucker Center for Cancer Care at Orange Regional Medical Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14623
      • Interlakes Oncology/Hematology PC
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
    • Wilson, North Carolina, United States, 27893-3428
      • Wilson Medical Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Independence, Ohio, United States, 44131
      • Community Oncology Group at Cleveland Clinic Cancer Center
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic - Wooster
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Cancer Center
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Lackland AFB, Texas, United States, 78236
      • Wilford Hall Medical Center
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy and Research Center
    • San Antonio, Texas, United States, 78209
      • Veterans Affairs Medical Center - San Antonio (Murphy)
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • University Hospital - San Antonio
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
  • Washington
    • Bellingham, Washington, United States, 98225
      • St. Joseph Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Mt. Vernon, Washington, United States, 98273
      • Skagit Valley Hospital Cancer Care Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical, PLLC
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Seattle, Washington, United States, 98122
      • Polyclinic First Hill
    • Seattle, Washington, United States, 98195-6043
      • University Cancer Center at University of Washington Medical Center
    • Sedro-Wooley, Washington, United States, 98284
      • North Puget Oncology at United General Hospital
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Wenatchee, Washington, United States, 98801-2028
      • Wenatchee Valley Medical Center
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 120 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: gemcitabine, paclitaxel	Drug: gemcitabine hydrochloride; Drug: paclitaxel; 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)

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Derek Raghavan, MD, PhD, FRACP, FACP, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start: July 1, 2001
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: August 10, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): August 11, 2016
• Last Update Submitted That Met QC Criteria: July 8, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: recurrent bladder cancer; stage IV bladder cancer; metastatic transitional cell cancer of the renal pelvis and ureter; recurrent transitional cell cancer of the renal pelvis and ureter; transitional cell carcinoma of the bladder; recurrent urethral cancer; urethral cancer associated with invasive bladder cancer; regional transitional cell cancer of the renal pelvis and ureter; anterior urethral cancer; posterior urethral cancer; adenocarcinoma of the bladder; squamous cell carcinoma of the bladder
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Ureteral Diseases; Urethral Diseases; Kidney Neoplasms; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Ureteral Neoplasms; Urethral Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Paclitaxel
• Other Study ID Numbers: CDR0000068837; U10CA032102 (U.S. NIH Grant/Contract); S0028 (Other Identifier: SWOG)