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
18 Years
N/A
Both
Bladder Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Urethral Cancer
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Pathologic Complete Response Rate by Transurethral Resection of Bladder Tumor (TURBT) and Imaging Studies After Chemotherapy
Outcome Description:
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.
Outcome Time Frame:
up to 12 weeks after registration (assessed within 8 weeks after completion of 3 cycles of chemotherapy )
Safety Issue:
No
Principal Investigator
Primo N. Lara, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of California, Davis
Authority:
United States: Federal Government
Study ID:
CDR0000256921
NCT ID:
NCT00045630
Start Date:
January 2003
Completion Date:
December 2011
Related Keywords:
- Bladder Cancer
- Transitional Cell Cancer of the Renal Pelvis and Ureter
- Urethral Cancer
- 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
- Urinary Bladder Neoplasms
- Urethral Neoplasms
- Carcinoma, Transitional Cell
- Kidney Neoplasms
- Ureteral Neoplasms
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
| University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| CCOP - Upstate Carolina | Spartanburg, South Carolina 29303 |
| CCOP - Wichita | Wichita, Kansas 67214-3882 |
| Hurley Medical Center | Flint, Michigan 48503 |
| CCOP - Michigan Cancer Research Consortium | Ann Arbor, Michigan 48106 |
| Saint Joseph Mercy Cancer Center | Ann Arbor, Michigan 48106-0995 |
| Oakwood Cancer Center at Oakwood Hospital and Medical Center | Dearborn, Michigan 48123-2500 |
| Genesys Hurley Cancer Institute | Flint, Michigan 48503 |
| Van Elslander Cancer Center at St. John Hospital and Medical Center | Grosse Pointe Woods, Michigan 48236 |
| Foote Hospital | Jackson, Michigan 49201 |
| Sparrow Regional Cancer Center | Lansing, Michigan 48912-1811 |
| Seton Cancer Institute - Saginaw | Saginaw, Michigan 48601 |
| St. John Macomb Hospital | Warren, Michigan 48093 |
| Providence Saint Joseph Medical Center - Burbank | Burbank, California 91505 |
| CCOP - Montana Cancer Consortium | Billings, Montana 59101 |
| CCOP - Western Regional, Arizona | Phoenix, Arizona 85006-2726 |
| University of Colorado Cancer Center at University of Colorado Health Sciences Center | Denver, Colorado 80010 |
| CCOP - Grand Rapids | Grand Rapids, Michigan 49503 |
| CCOP - Columbia River Oncology Program | Portland, Oregon 97225 |
| CCOP - Scott and White Hospital | Temple, Texas 76508 |
| USC/Norris Comprehensive Cancer Center and Hospital | Los Angeles, California 90033-0804 |
| Veterans Affairs Medical Center - Denver | Denver, Colorado 80220 |
| CCOP - St. Louis-Cape Girardeau | Saint Louis, Missouri 63141 |
| Utah Valley Regional Medical Center - Provo | Provo, Utah 84604 |
| University of California Davis Cancer Center | Sacramento, California 95817 |
| Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
| Markey Cancer Center at University of Kentucky Chandler Medical Center | Lexington, Kentucky 40536-0084 |
| Cancer Research Center at Boston Medical Center | Boston, Massachusetts 02118 |
| Swedish Cancer Institute at Swedish Medical Center - First Hill Campus | Seattle, Washington 98104 |
| Latter Day Saints Hospital | Salt Lake City, Utah 84143 |
| Via Christi Cancer Center at Via Christi Regional Medical Center | Wichita, Kansas 67214 |
| Legacy Emanuel Hospital and Health Center & Children's Hospital | Portland, Oregon 97227 |
| Banner Good Samaritan Medical Center | Phoenix, Arizona 85006 |
| Banner Thunderbird Medical Center | Phoenix, Arizona 85306 |
| North Colorado Medical Center | Greeley, Colorado 80631 |
| McKee Medical Center | Loveland, Colorado 80539 |
| Saint Anthony's Hospital at Saint Anthony's Health Center | Alton, Illinois 62002 |
| Good Samaritan Regional Health Center | Mt. Vernon, Illinois 62864 |
| Southwest Medical Center | Liberal, Kansas 67901 |
| Battle Creek Health System Cancer Care Center | Battle Creek, Michigan 49017 |
| Metropolitan Hospital | Grand Rapids, Michigan 49506 |
| Holland Community Hospital | Holland, Michigan 49423 |
| Hackley Hospital | Muskegon, Michigan 49443 |
| Munson Medical Center | Traverse City, Michigan 49684 |
| Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital | Gape Girardeau, Missouri 63701 |
| David C. Pratt Cancer Center at St. John's Mercy | St. Louis, Missouri 63141 |
| Northern Rockies Radiation Oncology Center | Billings, Montana 59101 |
| Hematology-Oncology Centers of the Northern Rockies - Billings | Billings, Montana 59101 |
| St. Vincent Healthcare | Billings, Montana 59101 |
| Deaconess Billings Clinic - Downtown | Billings, Montana 59101 |
| Bozeman Deaconess Hospital | Bozeman, Montana 59715 |
| St. James Community Hospital | Butte, Montana 59701 |
| Big Sky Oncology | Great Falls, Montana 59405 |
| St. Peter's Hospital | Helena, Montana 59601 |
| Kalispell Medical Oncology | Kalispell, Montana 59901 |
| Kalispell Regional Medical Center | Kalispell, Montana 59901 |
| Glacier Oncology, PLLC | Kalispell, Montana 59901 |
| Montana Cancer Center at St. Patrick Hospital and Health Sciences Center | Missoula, Montana 59802 |
| Montana Cancer Specialists at Montana Cancer Center | Missoula, Montana 59802 |
| Community Medical Center | Missoula, Montana 59801 |
| Wayne Memorial Hospital, Incorporated | Goldsboro, North Carolina 27534 |
| American Fork Hospital | American Fork, Utah 84003 |
| Logan Regional Hospital | Logan, Utah 84321 |
| Cottonwood Hospital Medical Center | Murray, Utah 84107 |
| McKay-Dee Hospital Center | Ogden, Utah 84403 |
| Utah Cancer Specialists at UCS Cancer Center | Salt Lake City, Utah 84106 |
| Olympic Hematology and Oncology | Bremerton, Washington 98310 |
| Skagit Valley Hospital Cancer Care Center | Mt. Vernon, Washington 98273 |
| University Cancer Center at University of Washington Medical Center | Seattle, Washington 98195 |
| Harborview Medical Center | Seattle, Washington 98104 |
| North Puget Oncology at United General Hospital | Sedro-Wooley, Washington 98284 |
| Cancer Care Northwest - Spokane South | Spokane, Washington 99202 |
| Spectrum Health Hospital - Butterworth Campus | Grand Rapids, Michigan 49503 |
| Decatur Memorial Hospital Cancer Care Institute | Decatur, Illinois 62526 |
| Cancer Center of Kansas, PA - Dodge City | Dodge City, Kansas 67801 |
| Bay Regional Medical Center | Bay City, Michigan 48708 |
| Mecosta County Medical Center | Big Rapids, Michigan 49307 |
| Providence Cancer Institute at Providence Hospital - Southfield Campus | Southfield, Michigan 48075 |
| Saint Francis Medical Center | Cape Girardeau, Missouri 63701 |
| Adirondack Cancer Care - Glens Falls | Glens Falls, New York 12801 |
| Wayne Radiation Oncology | Goldsboro, North Carolina 27534 |
| Wilson Medical Center | Wilson, North Carolina 27893-3428 |
| Forsyth Regional Cancer Center at Forsyth Medical Center | Winston-Salem, North Carolina 27103 |
| Legacy Mount Hood Medical Center | Gresham, Oregon 97030 |
| Providence Milwaukie Hospital | Milwaukie, Oregon 97222 |
| Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center | Portland, Oregon 97210 |
| Providence Cancer Center at Providence Portland Medical Center | Portland, Oregon 97213-2967 |
| Providence St. Vincent Medical Center | Portland, Oregon 97225 |
| Legacy Meridian Park Hospital | Tualatin, Oregon 97062 |
| Dixie Regional Medical Center - East Campus | Saint George, Utah 84770 |
| Danville Regional Medical Center | Danville, Virginia 24541 |
| Minor and James Medical, PLLC | Seattle, Washington 98104 |
| Polyclinic First Hill | Seattle, Washington 98122 |
| Southwest Washington Medical Center Cancer Center | Vancouver, Washington 98668 |
| Welch Cancer Center at Sheridan Memorial Hospital | Sheridan, Wyoming 82801 |
| Montrose Memorial Hospital Cancer Center | Montrose, Colorado 81401 |
| Regional Cancer Center at Singing River Hospital | Pascagoula, Mississippi 39581 |
| Cancer Center of Kansas, PA - Chanute | Chanute, Kansas 66720 |
| Cancer Center of Kansas, PA - El Dorado | El Dorado, Kansas 67042 |
| Cancer Center of Kansas, PA - Kingman | Kingman, Kansas 67068 |
| Cancer Center of Kansas, PA - Newton | Newton, Kansas 67114 |
| Cancer Center of Kansas, PA - Parsons | Parsons, Kansas 67357 |
| Cancer Center of Kansas, PA - Pratt | Pratt, Kansas 67124 |
| Tammy Walker Cancer Center at Salina Regional Health Center | Salina, Kansas 67401 |
| Cancer Center of Kansas, PA - Salina | Salina, Kansas 67401 |
| Cancer Center of Kansas, PA - Wellington | Wellington, Kansas 67152 |
| Cancer Center of Kansas, PA - Wichita | Wichita, Kansas 67214 |
| Associates in Womens Health, PA - North Review | Wichita, Kansas 67208 |
| Cancer Center of Kansas, PA - Medical Arts Tower | Wichita, Kansas 67208 |
| Cancer Center of Kansas, PA - Winfield | Winfield, Kansas 67156 |
| St. Joseph Cancer Center | Bellingham, Washington 98225 |
| Wenatchee Valley Medical Center | Wenatchee, Washington 98801-2028 |
| Regional Cancer Center at Memorial Medical Center | Springfield, Illinois 62781-0001 |
| Good Samaritan Cancer Center at Good Samaritan Hospital | Kearney, Nebraska 68848-1990 |
| Rutherford Hospital | Rutherfordton, North Carolina 28139 |
| AnMed Health Cancer Center | Anderson, South Carolina 29621 |
| Gibbs Regional Cancer Center at Spartanburg Regional Medical Center | Spartanburg, South Carolina 29303 |
| Lacks Cancer Center at Saint Mary's Health Care | Grand Rapids, Michigan 49503 |
| Great Falls, Montana 59405 | |
| Sletten Regional Cancer Institute at Benefis Healthcare | Great Falls, Montana 59405 |
| Banner Baywood Medical Center | Mesa, Arizona 85206 |
| Banner Desert Medical Center | Mesa, Arizona 85202 |
| Christus Schumpert Cancer Treatment Center | Shreveport, Louisiana 71101 |
| University of Tennessee Cancer Institute - Medical Center | Memphis, Tennessee 38104 |
| Cancer Center at Providence Alaska Medical Center | Anchorage, Alaska 99519-6604 |
| Shaw Cancer Center at Vail Valley Medical Center | Edwards, Colorado 81632 |
