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

Bladder Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00055835
• Other study ID #: CDR0000271309
• Secondary ID: S0121U10CA032102
• Status: Completed
• Phase: Phase 2
• First received: March 6, 2003
• Last updated: January 30, 2013
• Start date: November 2002
• Est. completion date: June 2006

Study information

• Verified date: January 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, 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: June 2006
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Bladder Cancer
• Urethral Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• carboplatin
*AUC=5 (by modified Calvert formula), IV, over 15 minutes; given q 21 days for a maximum of 3 cycles (1 cycle = 21 days)
• cisplatin
75 mg/m2 (maximum dose 150 mg), IV, rapid infusion; given q 21 days for 2 cycles (1 cycle = 21 days)
• gemcitabine hydrochloride
800 mg/m2, IV, over 30 minutes; given on Days 1 & 8, q 21 days, for a maximum of 3 cycles (1 cycle = 21 days)
• paclitaxel
200 mg/m2, IV, over 3 hours; given q 21 days for a maximum of 3 cycles (1 cycle = 21 days)

Procedure:
• neoadjuvant therapy
Neoadjuvant chemotherapy (paclitaxel, carboplatin, and gemcitabine)

Radiation:
• radiation therapy
Radiation treatments will be delivered once daily. Treatment will be given 5 days per week at a dose of 180 to 200 cGy per day. All fields will be treated everyday.

Locations

Country	Name	City	State
United States	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico
United States	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico
United States	Harrington Cancer Center	Amarillo	Texas
United States	Texas Tech University Health Sciences Center School of Medicine	Amarillo	Texas
United States	Veterans Affairs Medical Center - Amarillo	Amarillo	Texas
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Aurora	Colorado
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Cancer Research Center at Boston Medical Center	Boston	Massachusetts
United States	Western New York Urology Associates	Buffalo	New York
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Veterans Affairs Medical Center - Charleston	Charleston	South Carolina
United States	MBCCOP - University of Illinois at Chicago	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago Westside Hospital	Chicago	Illinois
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	CCOP - Dayton	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	CCOP - Central Illinois	Decatur	Illinois
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Josephine Ford Cancer Center at Henry Ford Health System	Detroit	Michigan
United States	Veterans Affairs Medical Center - Detroit	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	University of Texas Medical Branch	Galveston	Texas
United States	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	CCOP - Greenville	Greenville	South Carolina
United States	Veterans Affairs Medical Center - Hines	Hines	Illinois
United States	MBCCOP - Hawaii	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Veterans Affairs Medical Center - Little Rock	Little Rock	Arkansas
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	UMC Southwest Cancer and Research Center	Lubbock	Texas
United States	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	University of Tennessee Cancer Institute at Methodist Central Hospital	Memphis	Tennessee
United States	MBCCOP - Gulf Coast	Mobile	Alabama
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Tulane Cancer Center at Tulane University Hospital and Clinic	New Orleans	Louisiana
United States	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Sentara Cancer Institute at Sentara Norfolk General Hospital	Norfolk	Virginia
United States	CCOP - Bay Area Tumor Institute	Oakland	California
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California
United States	CCOP - Western Regional, Arizona	Phoenix	Arizona
United States	Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)	Phoenix	Arizona
United States	Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	CCOP - Beaumont	Royal Oak	Michigan
United States	University of California Davis Cancer Center	Sacramento	California
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas
United States	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Puget Sound Oncology Consortium	Seattle	Washington
United States	Veterans Affairs Medical Center - Seattle	Seattle	Washington
United States	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana
United States	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana
United States	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	CCOP - Northwest	Tacoma	Washington
United States	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Veterans Affairs Medical Center - Temple	Temple	Texas
United States	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona
United States	Veterans Affairs Medical Center - Tucson	Tucson	Arizona
United States	MBCCOP - Howard University Cancer Center	Washington	District of Columbia
United States	CCOP - Wichita	Wichita	Kansas
United States	Veterans Affairs Medical Center - Wichita	Wichita	Kansas

Sponsors (2)

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

Country where clinical trial is conducted

United States,