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

Bladder Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00045630
• Other study ID #: CDR0000256921
• Secondary ID: S0219U10CA032102
• Status: Completed
• Phase: Phase 2
• First received: September 6, 2002
• Last updated: April 16, 2013
• Start date: January 2003
• Est. completion date: December 2011

Study information

• Verified date: April 2013
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00191217

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: December 2011
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Transitional Cell
• Kidney Neoplasms
• Transitional Cell Cancer of the Renal Pelvis and Ureter
• Ureteral Neoplasms
• Urethral Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• carboplatin

• gemcitabine

• paclitaxel

Procedure:
• surgery

Locations

Country	Name	City	State
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	American Fork Hospital	American Fork	Utah
United States	Cancer Center at Providence Alaska Medical Center	Anchorage	Alaska
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	Bay Regional Medical Center	Bay City	Michigan
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Mecosta County Medical Center	Big Rapids	Michigan
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Deaconess Billings Clinic - Downtown	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare	Billings	Montana
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	St. James Community Hospital	Butte	Montana
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Danville Regional Medical Center	Danville	Virginia
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Shaw Cancer Center at Vail Valley Medical Center	Edwards	Colorado
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Gape Girardeau	Missouri
United States	Banner Thunderbird Medical Center	Glendale	Arizona
United States	Adirondack Cancer Care - Glens Falls	Glens Falls	New York
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Metropolitan Hospital	Grand Rapids	Michigan
United States	Spectrum Health Hospital - Butterworth Campus	Grand Rapids	Michigan
United States	Big Sky Oncology	Great Falls	Montana
United States	Sletten Regional Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	St. Peter's Hospital	Helena	Montana
United States	Holland Community Hospital	Holland	Michigan
United States	Foote Hospital	Jackson	Michigan
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Southwest Medical Center	Liberal	Kansas
United States	Logan Regional Hospital	Logan	Utah
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	McKee Medical Center	Loveland	Colorado
United States	University of Tennessee Cancer Institute - Medical Center	Memphis	Tennessee
United States	Banner Baywood Medical Center	Mesa	Arizona
United States	Banner Desert Medical Center	Mesa	Arizona
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Community Medical Center	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Montrose Memorial Hospital Cancer Center	Montrose	Colorado
United States	Good Samaritan Regional Health Center	Mt. Vernon	Illinois
United States	Skagit Valley Hospital Cancer Care Center	Mt. Vernon	Washington
United States	Cottonwood Hospital Medical Center	Murray	Utah
United States	Hackley Hospital	Muskegon	Michigan
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Banner Good Samaritan Medical Center	Phoenix	Arizona
United States	CCOP - Western Regional, Arizona	Phoenix	Arizona
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center & Children's Hospital	Portland	Oregon
United States	Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Utah Valley Regional Medical Center - Provo	Provo	Utah
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	University of California Davis Cancer Center	Sacramento	California
United States	Seton Cancer Institute - Saginaw	Saginaw	Michigan
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas
United States	Latter Day Saints Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical, PLLC	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	North Puget Oncology at United General Hospital	Sedro-Wooley	Washington
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Christus Schumpert Cancer Treatment Center	Shreveport	Louisiana
United States	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	CCOP - St. Louis-Cape Girardeau	St. Louis	Missouri
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Munson Medical Center	Traverse City	Michigan
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	St. John Macomb Hospital	Warren	Michigan
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wilson Medical Center	Wilson	North Carolina
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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; discuss — View 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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic Complete Response Rate by Transurethral Resection of Bladder Tumor (TURBT) and Imaging Studies After 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 )	No
Secondary	Overall Survival (OS)	Overall survival is defined from the date of registration to date of death from any cause	0-2 years	No
Secondary	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 at weeks 1, 2, 4, 5, 7, 8, and following surgery	Yes