S0219, Combination Chemotherapy Followed By Observation or Surgery in Patients With Stage II or Stage III Cancer of the Urothelium

April 16, 2013 updated by: Southwest Oncology Group

A Sequential Approach to the Treatment of Muscle Invasive, Non-Metastatic Urothelial Carcinoma of the Bladder: A Phase II Trial of Neoadjuvant Gemcitabine, Paclitaxel and Carboplatin With Molecular Correlates

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells and decrease the need for surgery.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by observation or surgery to remove the bladder (cystectomy) in treating patients who have stage II or stage III cancer of the urothelium.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the pathologic complete response of patients with stage II or III transitional cell cancer of the urothelium treated with neoadjuvant gemcitabine, paclitaxel, and carboplatin followed by observation or immediate cystectomy.
  • Determine, preliminarily, if molecular markers predict response, survival, and tumor recurrence in patients treated with these regimens.
  • Determine recurrence rates and cystectomy-free survival of patients who choose observation after an initial response to neoadjuvant chemotherapy.
  • Compare the survival of patients treated with neoadjuvant chemotherapy followed by cystectomy vs observation.
  • Determine the feasibility, tolerability, and toxicity of these regimens in these patients.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine IV over 30 minutes and paclitaxel IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Within 4-8 weeks after completion of neoadjuvant chemotherapy, patients undergo a third transurethral resection of bladder tumor.

Patients with T0 disease after neoadjuvant chemotherapy may choose to undergo observation. These patients undergo cystoscopies with biopsies every 3 months for 1 year, every 4 months for 1 year, and then every 6 months until disease progression.

Patients with T1 disease or greater after neoadjuvant chemotherapy undergo immediate cystectomy. Patients with T0 disease may also choose this option. Patients undergoing immediate cystectomy are followed every 6 months for 2 years and then annually for 3 years.

PROJECTED ACCRUAL: A total of 95 patients will be accrued for this study within 2 years.

Study Type

Interventional

Enrollment (Actual)

77

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alaska
      • Anchorage, Alaska, United States, 99519-6604
        • Cancer Center at Providence Alaska Medical Center
    • Arizona
      • Glendale, Arizona, United States, 85306
        • Banner Thunderbird Medical Center
      • Mesa, Arizona, United States, 85202
        • Banner Desert Medical Center
      • Mesa, Arizona, United States, 85206
        • Banner Baywood Medical Center
      • Phoenix, Arizona, United States, 85006
        • Banner Good Samaritan Medical Center
      • Phoenix, Arizona, United States, 85006
        • CCOP - Western Regional, Arizona
    • California
      • Burbank, California, United States, 91505
        • Providence Saint Joseph Medical Center - Burbank
      • Los Angeles, California, United States, 90089-9181
        • USC/Norris Comprehensive Cancer Center and Hospital
      • Sacramento, California, United States, 95817
        • University of California Davis Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center at University of Colorado Health Sciences Center
      • Denver, Colorado, United States, 80220
        • Veterans Affairs Medical Center - Denver
      • Edwards, Colorado, United States, 81632
        • Shaw Cancer Center at Vail Valley Medical Center
      • Greeley, Colorado, United States, 80631
        • North Colorado Medical Center
      • Loveland, Colorado, United States, 80539
        • McKee Medical Center
      • Montrose, Colorado, United States, 81401
        • Montrose Memorial Hospital Cancer Center
    • Illinois
      • Alton, Illinois, United States, 62002
        • Saint Anthony's Hospital at Saint Anthony's Health Center
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital Cancer Care Institute
      • Mt. Vernon, Illinois, United States, 62864
        • Good Samaritan Regional Health Center
      • 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
      • 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
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0293
        • Markey Cancer Center at University of Kentucky Chandler Medical Center
    • Louisiana
      • Shreveport, Louisiana, United States, 71101
        • Christus Schumpert Cancer Treatment Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Cancer Research Center at Boston Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0942
        • University of Michigan Comprehensive Cancer Center
      • Ann Arbor, Michigan, United States, 48106-0995
        • Saint Joseph Mercy Cancer Center
      • Ann Arbor, Michigan, United States, 48106
        • CCOP - Michigan Cancer Research Consortium
      • 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
      • Dearborn, Michigan, United States, 48123-2500
        • Oakwood Cancer Center at Oakwood Hospital and Medical Center
      • Detroit, Michigan, United States, 48201-1379
        • Barbara Ann Karmanos Cancer Institute
      • Flint, Michigan, United States, 48503
        • Hurley Medical Center
      • Flint, Michigan, United States, 48503
        • Genesys Hurley Cancer Institute
      • 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
      • Grosse Pointe Woods, Michigan, United States, 48236
        • Van Elslander Cancer Center at St. John Hospital and Medical Center
      • Holland, Michigan, United States, 49423
        • Holland Community Hospital
      • Jackson, Michigan, United States, 49201
        • Foote Hospital
      • Lansing, Michigan, United States, 48909
        • Sparrow Regional Cancer Center
      • Muskegon, Michigan, United States, 49443
        • Hackley Hospital
      • Saginaw, Michigan, United States, 48601
        • Seton Cancer Institute - Saginaw
      • Southfield, Michigan, United States, 48075
        • Providence Cancer Institute at Providence Hospital - Southfield Campus
      • Traverse City, Michigan, United States, 49684
        • Munson Medical Center
      • Warren, Michigan, United States, 48093
        • St. John Macomb Hospital
    • Mississippi
      • Pascagoula, Mississippi, United States, 39581
        • Regional Cancer Center at Singing River Hospital
    • Missouri
      • Cape Girardeau, Missouri, United States, 63701
        • Saint Francis Medical Center
      • Gape Girardeau, Missouri, United States, 63701
        • Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
      • Saint Louis, Missouri, United States, 63141
        • David C. Pratt Cancer Center at St. John's Mercy
      • St. Louis, Missouri, United States, 63141
        • CCOP - St. Louis-Cape Girardeau
    • 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
      • 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
    • Nebraska
      • Kearney, Nebraska, United States, 68848-1990
        • Good Samaritan Cancer Center at Good Samaritan Hospital
    • New York
      • Glens Falls, New York, United States, 12801
        • Adirondack Cancer Care - Glens Falls
    • 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
      • Winston-Salem, North Carolina, United States, 27103
        • Forsyth Regional Cancer Center at Forsyth Medical Center
    • Oregon
      • Gresham, Oregon, United States, 97030
        • Legacy Mount Hood Medical Center
      • Milwaukie, Oregon, United States, 97222
        • Providence Milwaukie Hospital
      • Portland, Oregon, United States, 97213-2967
        • Providence Cancer Center at Providence Portland Medical Center
      • Portland, Oregon, United States, 97225
        • CCOP - Columbia River Oncology Program
      • Portland, Oregon, United States, 97225
        • Providence St. Vincent Medical Center
      • Portland, Oregon, United States, 97210
        • Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel Hospital and Health Center & Children's Hospital
      • Tualatin, Oregon, United States, 97062
        • Legacy Meridian Park Hospital
    • 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
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • University of Tennessee Cancer Institute - Medical Center
    • Texas
      • Temple, Texas, United States, 76508
        • CCOP - Scott and White Hospital
    • Utah
      • American Fork, Utah, United States, 84003
        • American Fork Hospital
      • Logan, Utah, United States, 84321
        • Logan Regional Hospital
      • Murray, Utah, United States, 84107
        • Cottonwood Hospital Medical Center
      • Ogden, Utah, United States, 84403
        • McKay-Dee Hospital Center
      • Provo, Utah, United States, 84604
        • Utah Valley Regional Medical Center - Provo
      • Saint George, Utah, United States, 84770
        • Dixie Regional Medical Center - East Campus
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists at UCS Cancer Center
      • Salt Lake City, Utah, United States, 84143
        • Latter Day Saints 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
      • Vancouver, Washington, United States, 98668
        • Southwest Washington Medical Center Cancer Center
      • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed muscle-invasive (T2-T4a), node-negative (N0) urothelial transitional cell cancer (TCC) of the bladder
  • Focal squamous and/or adenocarcinoma differentiation, defined as ≤ 10% of tumor volume allowed

  • The following diagnoses are not allowed:

    • Small cell carcinoma
    • Sarcomatoid components

  • Disease diagnosed with an initial transurethral resection of bladder tumor (TURBT) and a second TURBT performed within 8 weeks of first with attempt to remove all tumor present

    • Residual disease after second TURBT allowed
    • No more than 14-56 days after second TURBT
  • No metastatic disease by chest x-ray and CT scan or MRI of the abdomen and pelvis
  • Fresh tumor tissue, paraffin tumor tissue, unstained slides, or cell block specimen from one or both TURBTs available

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • White blood cell count (WBC) at least 3,500/mm^3
  • Absolute granulocyte count at least 1,500/mm^3
  • Platelet count at least lower limit of normal

Hepatic

  • Bilirubin no greater than 1.5 mg/dL
  • Aspartate aminotransferase (SGOT) no greater than 2 times upper limit of normal

Renal

  • Creatinine no greater than 2.0 mg/dL AND/OR
  • Creatinine clearance at least 60 mL/min

Other

  • No prohibitive medical risk that would preclude radical cystectomy
  • No other serious concurrent systemic disorder that would preclude study compliance
  • No other malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, adequately treated stage I or II cancer in complete remission, or any other cancer for which patient has been disease-free for 5 years
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Prior intravesical immunotherapy allowed

Chemotherapy

  • No prior systemic chemotherapy for TCC of the urothelium
  • Prior intravesical chemotherapy allowed

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy for TCC of the urothelium
  • No concurrent radiotherapy

Surgery

  • See Disease Characteristics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Gemcitabine, Paclitaxel, Carboplatin
Gemcitabine, Paclitaxel, Carboplatin followed by surgery
Drug: carboplatin
Procedure: surgery
Drug: paclitaxel
Other Names:
  • Taxol
Drug: gemcitabine
Other Names:
  • gemcitabine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathologic Complete Response Rate by Transurethral Resection of Bladder Tumor (TURBT) and Imaging Studies After Chemotherapy
Time Frame: up to 12 weeks after registration (assessed within 8 weeks after completion of 3 cycles of chemotherapy )
Pathologic complete response (CR) is defined as absence of viable tumor in the TURBT specimen. Stable/No Response is defined as at least some disease evaluation tests were done (same tests as baseline) and status does not qualify for CR or Progression. Progression is defined as one or more of the following must occur: unequivocal progression of disease in the opinion of the treating physician. Appearance of any new lesion/site. Death due to disease without documented progression or symptomatic deterioration.
up to 12 weeks after registration (assessed within 8 weeks after completion of 3 cycles of chemotherapy )

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: 0-2 years
Overall survival is defined from the date of registration to date of death from any cause
0-2 years
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Time Frame: Patients were assessed for adverse events at weeks 1, 2, 4, 5, 7, 8, and following surgery
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 at weeks 1, 2, 4, 5, 7, 8, and following surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Southwest Oncology Group

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2003

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

September 6, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

May 27, 2013

Last Update Submitted That Met QC Criteria

April 16, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000256921
  • U10CA032102 (U.S. NIH Grant/Contract)
  • S0219 (Other Identifier: SWOG)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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