Clinical trial NCT00045630: S0219, Combination Chemotherapy Followed By Observation or Surgery in Patients With Stage II or Stage III Cancer of the Urothelium
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Transitional Cell Cancer of the Renal Pelvis and Ureter
Urethral Cancer
Keywords: anterior urethral cancer
localized transitional cell cancer of the renal pelvis and ureter
posterior urethral cancer
stage II bladder cancer
stage III bladder cancer
transitional cell carcinoma of the bladder
urethral cancer associated with invasive bladder cancer
regional transitional cell cancer of the renal pelvis and ureter
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pathologic Complete Response Rate by Transurethral Resection of Bladder Tumor (TURBT) and Imaging Studies After Chemotherapy
timeFrame: up to 12 weeks after registration (assessed within 8 weeks after completion of 3 cycles of chemotherapy )
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 0-2 years
measure: Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
timeFrame: Patients were assessed for adverse events at weeks 1, 2, 4, 5, 7, 8, and following surgery
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Cancer Center at Providence Alaska Medical Center
state: Alaska
city: Glendale
country: United States
facility: Banner Thunderbird Medical Center
state: Arizona
city: Mesa
country: United States
facility: Banner Desert Medical Center
state: Arizona
city: Mesa
country: United States
facility: Banner Baywood Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Banner Good Samaritan Medical Center
state: Arizona
city: Phoenix
country: United States
facility: CCOP - Western Regional, Arizona
state: Arizona
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center - Burbank
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at University of Colorado Health Sciences Center
state: Colorado
city: Denver
country: United States
facility: Veterans Affairs Medical Center - Denver
state: Colorado
city: Edwards
country: United States
facility: Shaw Cancer Center at Vail Valley Medical Center
state: Colorado
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Loveland
country: United States
facility: McKee Medical Center
state: Colorado
city: Montrose
country: United States
facility: Montrose Memorial Hospital Cancer Center
state: Colorado
city: Alton
country: United States
facility: Saint Anthony's Hospital at Saint Anthony's Health Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Mt. Vernon
country: United States
facility: Good Samaritan Regional Health Center
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Salina
country: United States
facility: Tammy Walker Cancer Center at Salina Regional Health Center
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Lexington
country: United States
facility: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: Shreveport
country: United States
facility: Christus Schumpert Cancer Treatment Center
state: Louisiana
city: Boston
country: United States
facility: Cancer Research Center at Boston Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Battle Creek
country: United States
facility: Battle Creek Health System Cancer Care Center
state: Michigan
city: Bay City
country: United States
facility: Bay Regional Medical Center
state: Michigan
city: Big Rapids
country: United States
facility: Mecosta County Medical Center
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Health Care
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospital - Butterworth Campus
state: Michigan
city: Grand Rapids
country: United States
facility: Metropolitan Hospital
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Holland
country: United States
facility: Holland Community Hospital
state: Michigan
city: Jackson
country: United States
facility: Foote Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Muskegon
country: United States
facility: Hackley Hospital
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute - Saginaw
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Institute at Providence Hospital - Southfield Campus
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Pascagoula
country: United States
facility: Regional Cancer Center at Singing River Hospital
state: Mississippi
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Gape Girardeau
country: United States
facility: Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
state: Missouri
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center at St. John's Mercy
state: Missouri
city: St. Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare
state: Montana
city: Billings
country: United States
facility: Deaconess Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Butte
country: United States
facility: St. James Community Hospital
state: Montana
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Great Falls
country: United States
facility: Sletten Regional Cancer Institute at Benefis Healthcare
state: Montana
city: Great Falls
country: United States
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Kearney
country: United States
facility: Good Samaritan Cancer Center at Good Samaritan Hospital
state: Nebraska
city: Glens Falls
country: United States
facility: Adirondack Cancer Care - Glens Falls
state: New York
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Radiation Oncology
state: North Carolina
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Wilson
country: United States
facility: Wilson Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Regional Cancer Center at Forsyth Medical Center
state: North Carolina
city: Gresham
country: United States
facility: Legacy Mount Hood Medical Center
state: Oregon
city: Milwaukie
country: United States
facility: Providence Milwaukie Hospital
state: Oregon
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center & Children's Hospital
state: Oregon
city: Tualatin
country: United States
facility: Legacy Meridian Park Hospital
state: Oregon
city: Anderson
country: United States
facility: AnMed Health Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Memphis
country: United States
facility: University of Tennessee Cancer Institute - Medical Center
state: Tennessee
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: American Fork
country: United States
facility: American Fork Hospital
state: Utah
city: Logan
country: United States
facility: Logan Regional Hospital
state: Utah
city: Murray
country: United States
facility: Cottonwood Hospital Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists at UCS Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: Latter Day Saints Hospital
state: Utah
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Bellingham
country: United States
facility: St. Joseph Cancer Center
state: Washington
city: Bremerton
country: United States
facility: Olympic Hematology and Oncology
state: Washington
city: Mt. Vernon
country: United States
facility: Skagit Valley Hospital Cancer Care Center
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Minor and James Medical, PLLC
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: Polyclinic First Hill
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Sedro-Wooley
country: United States
facility: North Puget Oncology at United General Hospital
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Vancouver
country: United States
facility: Southwest Washington Medical Center Cancer Center
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: University of California, Davis
name: Primo N. Lara, MD
role: STUDY_CHAIR
References:
citation: deVere White RW, Lara PN Jr, Goldman B, Tangen CM, Smith DC, Wood DP Jr, Hussain MH, Crawford ED. A sequential treatment approach to myoinvasive urothelial cancer: a phase II Southwest Oncology Group trial (S0219). J Urol. 2009 Jun;181(6):2476-80; discussion 2480-1. doi: 10.1016/j.juro.2009.01.115. Epub 2009 Apr 16.
citation: Lara PN, Goldman B, De Vere White R, et al.: A sequential treatment approach to muscle-invasive urothelial cancer: A phase II Southwest Oncology Group trial (S0219) of neoadjuvant paclitaxel, carboplatin, and gemcitabine (PCG). [Abstract] J Clin Oncol 26 (Suppl 15): A-5022, 2008.