Clinical trial NCT00238420: Paclitaxel and Radiation Therapy With or Without Trastuzumab in Treating Patients Who Have Undergone Surgery for Bladder Cancer
Official title: A Phase I/II Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation Following Transurethral Surgery for Non-Cystectomy Candidates With Muscle-Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Bladder Urothelial Carcinoma
Stage I Bladder Cancer AJCC v6 and v7
Stage II Bladder Cancer AJCC v6 and v7
Stage III Bladder Cancer AJCC v6 and v7
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Radiation Therapy Oncology Group
First posted: 2005-10-13
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase I/II trial is studying the side effects of giving paclitaxel together with radiation therapy with or without trastuzumab and to see how well it works to kill any remaining tumor cells in patients who have undergone surgery for bladder cancer. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Paclitaxel may also make tumor cells more sensitive to radiation therapy. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving paclitaxel together with radiation therapy and trastuzumab may kill more tumor cells. Giving these treatments after surgery may kill any remaining tumor cells.

Detailed description: PRIMARY OBJECTIVES:

I. To determine the acute toxicity (=\< 90 days from protocol treatment start) from chemoradiotherapy including paclitaxel +/- trastuzumab and irradiation in non-cystectomy patients with or without her2/neu overexpression.

SECONDARY OBJECTIVES:

I. To determine the ability of patients with bladder cancer who are non-cystectomy candidates to complete this treatment program.

II. To evaluate the efficacy of this treatment program in achieving a complete response of the primary tumor.

III. To measure the 5-year disease-free and overall survival of patients with bladder cancer treated with transurethral resection of the bladder followed by chemoradiotherapy.

IV. To estimate the value of tumor and/or serum biomarkers as predictors of initial tumor response and recurrence-free survival.

OUTLINE: This is a non-randomized, multicenter study. Patients are assigned to 1 of 2 treatment groups according to HER2/neu status (HER2/neu 2+ or 3+ staining \[group 1\] vs HER2/neu 0 or 1+ staining \[group 2\]).

GROUP I: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, 36, and 43 and trastuzumab (Herceptin®) IV over 90 minutes on day 1 and then over 30 minutes on days 8, 15, 22, 29, 36, and 43. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50. Treatment continues in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive paclitaxel and undergo radiotherapy as in group 1.

After completion of study treatment, patients are followed at 4-5 weeks, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed primary transitional cell carcinoma (TCC) of the bladder

  * Histologic evidence of muscularis propria invasion
* Meets 1 of the following stage criteria:

  * Stage T2-4a; NX, N0, or N1; and M0 disease
  * Clinical stage T1, grade 3/3 disease AND requires definitive local therapy
* Tumor involvement of the prostatic urethra allowed provided the following criteria are met:

  * Tumor was visibly completely resected
  * No evidence of stromal invasion of the prostate
  * No evidence of distant metastases by chest x-ray (or chest CT scan) within 8 weeks prior to registration
  * No evidence of distant metastases by abdominal/pelvic CT scan (or MRI scan) within 8 weeks prior to registration
* Has undergone transurethral bladder resection (as thorough as is judged safely possible) within the past 3-8 weeks, including bimanual examination with tumor mapping
* Sufficient tumor tissue available for HER2/neu analysis
* Not a candidate for radical cystectomy
* Performance status - Zubrod 0-2
* Absolute neutrophil count \>= 1,800/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \>= 8.0 g/dL (transfusion or other intervention allowed)
* Bilirubin \< 2.0 mg/dL
* Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) \< 2.5 times upper limit of normal
* No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
* Creatinine =\< 3.0 mg/dL
* Left ventricular ejection fraction (LVEF) \>= 40% by multigated acquisition scan (MUGA) scan or echocardiogram
* No unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
* No transmural myocardial infarction within the past 6 months
* Not pregnant or nursing
* No nursing for 6 months after completion of study treatment (for patients receiving trastuzumab \[Herceptin®\])
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 6 months after completion of study treatment
* Able to tolerate systemic chemotherapy and pelvic radiotherapy
* No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
* No history of allergic reaction to study drugs
* No history of inflammatory bowel disease
* No acute bacterial or fungal infection requiring IV antibiotics
* No AIDS
* No other severe active comorbidity
* No prior systemic chemotherapy with anthracyclines or taxanes
* No prior systemic chemotherapy for TCC
* No prior pelvic radiotherapy

Primary outcomes:
measure: Acute Treatment-related Toxicity
timeFrame: From start of protocol treatment to 90 days
Secondary outcomes:
measure: Treatment Completion
timeFrame: From registration to end of treatment; up to 64 days."
measure: Complete Response to Treatment
timeFrame: At 12 weeks from treatment start
measure: Progression-free Survival
timeFrame: From start of treatment to last follow-up. Maximum follow-up at time of analysis was 9.9 years.
measure: Overall Survival
timeFrame: From the date of treatment started to death, assessed up to at least 5 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Auburn
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Auburn
state: California
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center/Disney Family Cancer Center
state: California
city: Cameron Park
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Cameron Park
state: California
city: Carmichael
country: United States
facility: Mercy San Juan Medical Center
state: California
city: Roseville
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Roseville
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center Sacramento
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital Radiation Oncology Center
state: California
city: Vacaville
country: United States
facility: Sutter Cancer Centers Radiation Oncology Services-Vacaville
state: California
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Pueblo
country: United States
facility: The Reverend Roger Patrick Dorcy Cancer Center at Saint Mary-Corwin Medical Center
state: Colorado
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Wilmington
country: United States
facility: Saint Francis Hospital - Wilmington
state: Delaware
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Science Center - Jacksonville
state: Florida
city: Jupiter
country: United States
facility: Jupiter Medical Center
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Panama City
country: United States
facility: Bay Medical Center
state: Florida
city: Aurora
country: United States
facility: Rush - Copley Medical Center
state: Illinois
city: Bloomington
country: United States
facility: Saint Joseph Medical Center
state: Illinois
city: Bloomington
country: United States
facility: Illinois CancerCare-Bloomington
state: Illinois
city: Canton
country: United States
facility: Graham Hospital Association
state: Illinois
city: Canton
country: United States
facility: Illinois CancerCare-Canton
state: Illinois
city: Carthage
country: United States
facility: Illinois CancerCare-Carthage
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Decatur
country: United States
facility: Heartland Cancer Research NCORP
state: Illinois
city: Eureka
country: United States
facility: Eureka Hospital
state: Illinois
city: Eureka
country: United States
facility: Illinois CancerCare-Eureka
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare-Galesburg
state: Illinois
city: Galesburg
country: United States
facility: Western Illinois Cancer Treatment Center
state: Illinois
city: Havana
country: United States
facility: Illinois CancerCare-Havana
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex - Hospital
state: Illinois
city: Joliet
country: United States
facility: Duly Health and Care Joliet
state: Illinois
city: Kewanee
country: United States
facility: Illinois CancerCare-Kewanee Clinic
state: Illinois
city: Kewanee
country: United States
facility: Kewanee Hospital
state: Illinois
city: Macomb
country: United States
facility: Illinois CancerCare-Macomb
state: Illinois
city: Macomb
country: United States
facility: Mcdonough District Hospital
state: Illinois
city: Monmouth
country: United States
facility: Holy Family Medical Center
state: Illinois
city: Monmouth
country: United States
facility: Illinois CancerCare-Monmouth
state: Illinois
city: Normal
country: United States
facility: Bromenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Carle Cancer Institute Normal
state: Illinois
city: Normal
country: United States
facility: Illinois CancerCare-Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Illinois CancerCare-Ottawa Clinic
state: Illinois
city: Ottawa
country: United States
facility: Ottawa Regional Hospital and Healthcare Center
state: Illinois
city: Pekin
country: United States
facility: Illinois CancerCare-Pekin
state: Illinois
city: Pekin
country: United States
facility: OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
state: Illinois
city: Pekin
country: United States
facility: Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Radiation Oncology at Peoria Cancer Center
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois CancerCare-Peru
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Hospital
state: Illinois
city: Peru
country: United States
facility: Valley Radiation Oncology
state: Illinois
city: Princeton
country: United States
facility: Illinois CancerCare-Princeton
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: Illinois CancerCare-Spring Valley
state: Illinois
city: Spring Valley
country: United States
facility: Saint Margaret's Hospital
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Fort Wayne
country: United States
facility: Radiation Oncology Associates PC
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Hospital Randallia
state: Indiana
city: Michigan City
country: United States
facility: Franciscan Saint Anthony Health-Michigan City
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic PC - Ames
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Iowa-Wide Oncology Research Coalition NCORP
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Laurel
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Lutheran Hospital
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Regional Cancer Center
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center-Sioux City
state: Iowa
city: Sioux City
country: United States
facility: Saint Luke's Regional Medical Center
state: Iowa
city: Dodge City
country: United States
facility: Cancer Center of Kansas - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas - El Dorado
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates In Womens Health
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas-Wichita Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Ascension Via Christi Hospitals Wichita
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas - Wichita
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wichita NCI Community Oncology Research Program
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas - Winfield
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Elkton
country: United States
facility: Christiana Care - Union Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Fall River
country: United States
facility: Saint Anne's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Pascagoula
country: United States
facility: Singing River Hospital
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: Montana Cancer Consortium NCORP
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Great Falls
country: United States
facility: Benefis Healthcare- Sletten Cancer Institute
state: Montana
city: Great Falls
country: United States
facility: Berdeaux, Donald MD (UIA Investigator)
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Cancer Institute-Summerlin Campus
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation NCORP
state: Nevada
city: Keene
country: United States
facility: Cheshire Medical Center-Dartmouth-Hitchcock Keene
state: New Hampshire
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: Mount Holly
country: United States
facility: Virtua Memorial
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Vineland
country: United States
facility: Inspira Medical Center Vineland
state: New Jersey
city: Poughkeepsie
country: United States
facility: Hudson Valley Oncology Associates
state: New York
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Kinston
country: United States
facility: Vidant Oncology-Kinston
state: North Carolina
city: Bismarck
country: United States
facility: Mid Dakota Clinic
state: North Dakota
city: Bismarck
country: United States
facility: Saint Alexius Medical Center
state: North Dakota
city: Bismarck
country: United States
facility: Sanford Bismarck Medical Center
state: North Dakota
city: Akron
country: United States
facility: Summa Health System - Akron Campus
state: Ohio
city: Akron
country: United States
facility: Cleveland Clinic Akron General
state: Ohio
city: Barberton
country: United States
facility: Summa Health System - Barberton Campus
state: Ohio
city: Canton
country: United States
facility: Cleveland Clinic Mercy Hospital
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Salem
country: United States
facility: UH Seidman Cancer Center at Salem Regional Medical Center
state: Ohio
city: Springfield
country: United States
facility: Springfield Regional Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Clackamas
country: United States
facility: Clackamas Radiation Oncology Center
state: Oregon
city: Milwaukie
country: United States
facility: Providence Milwaukie Hospital
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Saint Vincent Medical Center
state: Oregon
city: Drexel Hill
country: United States
facility: Delaware County Memorial Hospital
state: Pennsylvania
city: Dunmore
country: United States
facility: Northeast Radiation Oncology Center
state: Pennsylvania
city: Furlong
country: United States
facility: Fox Chase Cancer Center Buckingham
state: Pennsylvania
city: Media
country: United States
facility: Riddle Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: Main Line Health NCORP
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Cedar City
country: United States
facility: Sandra L Maxwell Cancer Center
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: Murray
country: United States
facility: Intermountain 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
state: Utah
city: Saint George
country: United States
facility: Saint George Regional Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists-Salt Lake City
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Saint Johnsbury
country: United States
facility: Norris Cotton Cancer Center-North
state: Vermont
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Federal Way
country: United States
facility: Saint Francis Hospital
state: Washington
city: Kirkland
country: United States
facility: EvergreenHealth Medical Center
state: Washington
city: Puyallup
country: United States
facility: MultiCare Good Samaritan Hospital
state: Washington
city: Renton
country: United States
facility: Valley Medical Center
state: Washington
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Tacoma
country: United States
facility: MultiCare Tacoma General Hospital
state: Washington
city: Tacoma
country: United States
facility: Northwest NCI Community Oncology Research Program
state: Washington
city: Tacoma
country: United States
facility: Saint Joseph Medical Center
state: Washington
city: Vancouver
country: United States
facility: PeaceHealth Southwest Medical Center
state: Washington
city: Vancouver
country: United States
facility: Compass Oncology Vancouver
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Sheridan
country: United States
facility: Welch Cancer Center
state: Wyoming
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Saint John
country: Canada
facility: Atlantic Health Sciences Corporation-Saint John Regional Hospital
state: New Brunswick
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
Study officials:
affiliation: Radiation Therapy Oncology Group
name: M. D Michaelson
role: PRINCIPAL_INVESTIGATOR
References: