S0121, Neoadjuvant Carboplatin, Paclitaxel, and Gemcitabine Followed by Cisplatin and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Carcinoma of the Urothelium

Phase II Evaluation of Carboplatin, Paclitaxel and Gemcitabine Followed by Concurrent Cisplatin and Radiation Therapy in Patients With Locally Advanced or Recurrent Urothelial Malignancy

RATIONALE: Drugs used in chemotherapy, such as carboplatin, paclitaxel, gemcitabine, and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving chemotherapy before radiation therapy, and combining chemotherapy with radiation therapy, may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of neoadjuvant gemcitabine, paclitaxel, and carboplatin followed by cisplatin and radiation therapy in treating patients who have locally advanced or recurrent carcinoma (cancer) of the urothelium.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer; Urethral Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: cisplatin; Drug: gemcitabine hydrochloride; Drug: paclitaxel; Procedure: neoadjuvant therapy; Radiation: radiation therapy

Detailed Description

OBJECTIVES:

• Determine the overall survival of patients with locally advanced or recurrent carcinoma of the urothelium treated with neoadjuvant carboplatin, paclitaxel, and gemcitabine followed by concurrent cisplatin and radiotherapy.
• Determine the feasibility of administering this regimen to these patients.
• Determine the progression-free survival of patients treated with this regimen.
• Determine the qualitative and quantitative toxic effects of this regimen in these patients.
• Determine the response rate (confirmed and unconfirmed) of patients treated with the neoadjuvant regimen and those treated with the whole regimen.
• Determine the proportion of patients who qualify for concurrent cisplatin and radiotherapy after receiving the neoadjuvant regimen.
• Determine the potential value of suppressor gene expression analysis (p53 and retinoblastoma gene) and HER2 expression as indicators of prognosis and/or response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive neoadjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 15 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for a maximum of 3 courses in the absence of disease progression or unacceptable toxicity.

Within 4-8 weeks after the completion of neoadjuvant chemotherapy, patients receive cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for a maximum of 2 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo concurrent radiotherapy 5 days a week for 6 weeks.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 4 years.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36607
      • MBCCOP - Gulf Coast
  • Arizona
    • Phoenix, Arizona, United States, 85006-2726
      • CCOP - Western Regional, Arizona
    • Phoenix, Arizona, United States, 85012
      • Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)
    • Tucson, Arizona, United States, 85723
      • Veterans Affairs Medical Center - Tucson
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center at University of Arizona Health Sciences Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
    • Little Rock, Arkansas, United States, 72205
      • Veterans Affairs Medical Center - Little Rock
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Martinez, California, United States, 94553
      • Veterans Affairs Outpatient Clinic - Martinez
    • Oakland, California, United States, 94609-3305
      • CCOP - Bay Area Tumor Institute
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Santa Rosa, California, United States, 95403
      • CCOP - Santa Rosa Memorial Hospital
  • Colorado
    • Aurora, Colorado, United States, 80010
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
    • Denver, Colorado, United States, 80220
      • Veterans Affairs Medical Center - Denver
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • MBCCOP - Howard University Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Veterans Affairs Medical Center - Tampa (Haley)
  • Georgia
    • Atlanta, Georgia, United States, 30342-1701
      • CCOP - Atlanta Regional
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • MBCCOP - Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60612
      • MBCCOP - University of Illinois at Chicago
    • Chicago, Illinois, United States, 60612
      • Veterans Affairs Medical Center - Chicago Westside Hospital
    • Decatur, Illinois, United States, 62526
      • CCOP - Central Illinois
    • Hines, Illinois, United States, 60141
      • Veterans Affairs Medical Center - Hines
    • Maywood, Illinois, United States, 60153-5500
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160-7390
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67218
      • Veterans Affairs Medical Center - Wichita
  • Kentucky
    • Lexington, Kentucky, United States, 40502-2236
      • Veterans Affairs Medical Center - Lexington
    • Lexington, Kentucky, United States, 40536-0084
      • Markey Cancer Center at University of Kentucky Chandler Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Veterans Affairs Medical Center - New Orleans
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center at Tulane University Hospital and Clinic
    • Shreveport, Louisiana, United States, 71130-3932
      • Feist-Weiller Cancer Center at Louisiana State University Health Sciences
    • Shreveport, Louisiana, United States, 71101-4295
      • Veterans Affairs Medical Center - Shreveport
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Cancer Research Center at Boston Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Ann Arbor, Michigan, United States, 48109-0946
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48201-1932
      • Veterans Affairs Medical Center - Detroit
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Health System
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Royal Oak, Michigan, United States, 48073-6769
      • CCOP - Beaumont
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Institute at Providence Hospital - Southfield Campus
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
    • Jackson, Mississippi, United States, 39216
      • Veterans Affairs Medical Center - Jackson
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center
    • Springfield, Missouri, United States, 65807
      • CCOP - Cancer Research for the Ozarks
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108-5138
      • Veterans Affairs Medical Center - Albuquerque
    • Albuquerque, New Mexico, United States, 87131
      • MBCCOP - University of New Mexico HSC
  • New York
    • Buffalo, New York, United States, 14220
      • Western New York Urology Associates
    • New York, New York, United States, 10016
      • NYU Cancer Institute at New York University Medical Center
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534-9479
      • CCOP - Southeast Cancer Control Consortium
  • Ohio
    • Cincinnati, Ohio, United States, 45220-2288
      • Veterans Affairs Medical Center - Cincinnati
    • Cincinnati, Ohio, United States, 45267-0501
      • Charles M. Barrett Cancer Center at University Hospital
    • Cleveland, Ohio, United States, 44195-9001
      • Cleveland Clinic Taussig Cancer Center
    • Columbus, Ohio, United States, 43206
      • CCOP - Columbus
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Dayton, Ohio, United States, 45428-1002
      • Veterans Affairs Medical Center - Dayton
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97201-3098
      • Cancer Institute at Oregon Health and Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Charleston, South Carolina, United States, 29401-5799
      • Veterans Affairs Medical Center - Charleston
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • University of Tennessee Cancer Institute at Methodist Central Hospital
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Tech University Health Sciences Center School of Medicine
    • Amarillo, Texas, United States, 79106
      • Harrington Cancer Center
    • Amarillo, Texas, United States, 79106
      • Veterans Affairs Medical Center - Amarillo
    • Fort Sam Houston, Texas, United States, 78234-6200
      • Brooke Army Medical Center
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030-4095
      • M.D. Anderson Cancer Center at University of Texas
    • Lubbock, Texas, United States, 79415-3364
      • UMC Southwest Cancer and Research Center
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78229
      • Veterans Affairs Medical Center - San Antonio (Murphy)
    • Temple, Texas, United States, 76504
      • Veterans Affairs Medical Center - Temple
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84148
      • Veterans Affairs Medical Center - Salt Lake City
    • Salt Lake City, Utah, United States, 84112-5550
      • Huntsman Cancer Institute at University of Utah
  • Virginia
    • Norfolk, Virginia, United States, 23510-1115
      • Sentara Cancer Institute at Sentara Norfolk General Hospital
  • Washington
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Seattle, Washington, United States, 98108
      • Veterans Affairs Medical Center - Seattle
    • Seattle, Washington, United States, 98109
      • Puget Sound Oncology Consortium
    • Tacoma, Washington, United States, 98405-0986
      • CCOP - Northwest

Participation Criteria

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 primary or recurrent invasive carcinoma of the urothelium

  • Transitional, squamous, or mixed cell subtypes allowed
  • Primary disease site must be the urinary bladder or urethra
  • Disease confined to the true pelvis (T2-T4, N0-N3, M0)

  • Must meet at least 1 of the following criteria:

    • Nodal involvement at or below the level of the bifurcation of the iliac vessels
    • Medically or surgically inoperable
    • Patient refused cystectomy
• Measurable or nonmeasurable disease
• Evidence of tumor invasion of the muscularis by cystoscopy and biopsy and detailed bladder mapping within the past 56 days
• No extrapelvic metastases

• Eligible to receive radiotherapy

  • Planned radiotherapy at a SWOG-approved facility

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least lower limit of normal

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• SGOT or SGPT no greater than 2.5 times ULN

Renal

• Creatinine clearance at least 60 mL/min OR
• Creatinine no greater than ULN

Gastrointestinal

• No chronic diarrhea
• No malabsorption
• No extensive diverticular disease of the colon
• No inflammatory bowel disease
• No other pre-existing gastrointestinal disorders

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No active infections requiring antibiotics
• No other 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 currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for patients with a current diagnosis of advanced bladder cancer that is also the initial diagnosis
• No prior systemic chemotherapy except adjuvant therapy for recurrent disease completed more than 6 months ago
• No prior carboplatin
• No prior paclitaxel
• No prior gemcitabine

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• No prior pelvic radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Study Plan

How is the study designed?

Design Details

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

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Ulka N. Vaishampayan, MD, Barbara Ann Karmanos Cancer Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2002
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: March 6, 2003
• First Submitted That Met QC Criteria: March 6, 2003
• First Posted (Estimate): March 7, 2003

Study Record Updates

• Last Update Posted (Estimate): January 31, 2013
• Last Update Submitted That Met QC Criteria: January 30, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: stage III bladder cancer; recurrent bladder cancer; stage IV bladder cancer; transitional cell carcinoma of the bladder; distal urethral cancer; proximal urethral cancer; recurrent urethral cancer; urethral cancer associated with invasive bladder cancer; stage II bladder cancer; squamous cell carcinoma of the bladder
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urethral Diseases; Urinary Bladder 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; Carboplatin; Paclitaxel; Cisplatin
• Other Study ID Numbers: CDR0000271309; U10CA032102 (U.S. NIH Grant/Contract); S0121 (Other Identifier: SWOG)