Clinical trial NCT02316548: Surgery With or Without Postoperative Intensity Modulated Radiation Therapy in Treating Patients With Urothelial Bladder Cancer
Official title: Randomized Phase II Trial of Postoperative Adjuvant IMRT Following Cystectomy for pT3/T4 Urothelial Bladder Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Stage III Bladder Cancer
Stage IV Bladder Cancer
Lead sponsor: NRG Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-12-15
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase II trial studies the side effects and how well postoperative intensity modulated radiotherapy works after surgery in treating patients with urothelial bladder cancer. Radiation therapy uses high energy x-rays to kill tumor cells left behind in the pelvis after surgery. It is not yet known whether surgery followed by radiotherapy is more effective than surgery alone in treating patients with urothelial bladder cancer.

Detailed description: PRIMARY OBJECTIVE:

I. To evaluate the ability of postcystectomy adjuvant radiotherapy to safely reduce pelvic tumor recurrence, defined as pelvic recurrence-free survival.

SECONDARY OBJECTIVES:

I. Evaluate increase in disease-free survival. II. Evaluate toxicity of adjuvant pelvic radiotherapy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms. Patients are stratified by neoadjuvant preoperative or postoperative adjuvant chemotherapy.

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

Eligibility criteria: Inclusion Criteria (A patient cannot be considered eligible for this study unless ALL of the following conditions are met.):

* Initial histological diagnosis of muscle invasive urothelial carcinoma
* Patients must have undergone a radical cystectomy (reconstructed urinary diversion may be non-continent diversions (eg, ileal conduits) or continent non-orthotopic catheterizable diversions (eg, Indiana pouch) or continent orthotopic diversions (eg, Studer pouch or neobladder)for urothelial bladder carcinoma within 105 days prior to registration. Final cystectomy pathology must be either pure urothelial carcinoma or dominant urothelial carcinoma with admixture of other histologies excluding small cell variants.

  * Neoadjuvant (preoperative) or adjuvant (postoperative) chemotherapy for the bladder cancer is permitted; however, all patients, even those who will receive adjuvant chemotherapy, must be registered within 105 days after completing cystectomy regardless of whether adjuvant chemotherapy has started. Patients who will be receiving adjuvant (postoperative) chemotherapy will be randomized within 28 days of completing that chemotherapy.
* Patients with the following pTNM stages per the American Joint Committee on Cancer (AJCC) 7th ed. are eligible:

  * pT3apN0; pN1; pN2 provided less than 10 nodes dissected and/or positive surgical margins
  * pT3bpN0; pN1; pN2
  * pT4apN0; pN1; pN2
  * pT4bpN0; pN1; pN2
* Appropriate stage for study entry based on the following diagnostic workup:

  * History/physical examination =\< 45 days prior to registration;
  * CT or MRI or positron emission tomography(PET)-CT that includes chest, abdomen and pelvis should be performed for initial radiological staging. This may be performed pre- or post-surgery ≤ 90 days prior to registration except in patients getting postoperative adjuvant chemotherapy, who will require CT, MRI or PET-CT including the chest and abdomen and pelvis no more than 30 days prior to registration. Imaging performed postoperatively should show no evidence of residual disease.
* Age \>=18
* Zubrod performance status 0-2 =\< 45 days prior to registration
* Complete blood count (CBC)/differential obtained ≤ 14 days prior to registration with adequate bone marrow function defined as follows:

  * Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3
  * Platelets \>= 100,000 cells/mm\^3
  * Hemoglobin \>= 8.0 g/dl (NOTE: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 8.0 g/dl is acceptable)
  * The patient must provide study-specific informed consent prior to study entry
* The patient must provide study-specific informed consent prior to study entry.

Exclusion Criteria (Patients with any of the following conditions are NOT eligible for this study.):

* Definitive clinical or radiologic evidence of metastatic disease; pN3 disease is not allowed (positive common iliac node).
* Prior invasive solid tumor or hematological malignancy (except non-melanomatous skin cancer and incidentally discovered prostate cancer at time of cystoprostatectomy) unless disease free for a minimum of 3 years
* Prior radiotherapy to the pelvis
* Patients with a history of inflammatory bowel disease
* Patients who have required any treatment (medical or surgical) for bowel obstruction prior to diagnosis of bladder cancer or who have required surgical treatment for bowel obstruction after the cystectomy
* Severe, active co-morbidity defined as follows:

  * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
  * Transmural myocardial infarction within the last 6 months;
  * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
  * Severe hepatic disease, defined as a diagnosis of Child-Pugh Class B or C hepatic disease;
  * HIV positive with CD4 count \< 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol.
  * Other major medical illness which requires hospitalization or precludes study therapy at the time of registration.
* Women who are breastfeeding

Primary outcomes:
measure: Pelvic Recurrence-free Survival (PRFS)
timeFrame: From randomization to study termination, maximum follow-up was 13.3 months, median follow-up was 1.9 months
Secondary outcomes:
measure: Disease Free Survival (DFS)
timeFrame: From randomization to study termination, maximum follow-up was 13.3 months, median follow-up was 1.9 months
measure: Number of Patients With Bowel Toxicity
timeFrame: From randomization to study termination, maximum follow-up was 13.3 months, median follow-up was 1.9 months
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: AIS Cancer Center at San Joaquin Community Hospital
state: California
city: Greenbrae
country: United States
facility: Marin General Hospital
state: California
city: Los Angeles
country: United States
facility: Los Angeles General Medical Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute Palo Alto
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: UCHealth University of Colorado Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Colorado Springs
country: United States
facility: UCHealth Memorial Hospital Central
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Rehoboth Beach
country: United States
facility: Beebe Health Campus
state: Delaware
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center-Gainesville
state: Georgia
city: Savannah
country: United States
facility: Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
state: Georgia
city: Boise
country: United States
facility: Saint Luke's Cancer Institute - Boise
state: Idaho
city: Fruitland
country: United States
facility: Saint Luke's Cancer Institute - Fruitland
state: Idaho
city: Meridian
country: United States
facility: Saint Luke's Cancer Institute - Meridian
state: Idaho
city: Nampa
country: United States
facility: Saint Luke's Cancer Institute - Nampa
state: Idaho
city: Twin Falls
country: United States
facility: Saint Luke's Cancer Institute - Twin Falls
state: Idaho
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Pekin
country: United States
facility: OSF Saint Francis Radiation Oncology at Pekin
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: OSF Saint Francis Medical Center
state: Illinois
city: Springfield
country: United States
facility: Springfield Memorial Hospital
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: Goshen
country: United States
facility: Goshen Center for Cancer Care
state: Indiana
city: Mishawaka
country: United States
facility: Memorial Regional Cancer Center Day Road
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic - Ames
state: Iowa
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: Wichita
country: United States
facility: Ascension Via Christi Hospitals Wichita
state: Kansas
city: Louisville
country: United States
facility: Norton Hospital Pavilion and Medical Campus
state: Kentucky
city: Louisville
country: United States
facility: UofL Health Medical Center Northeast
state: Kentucky
city: Scarborough
country: United States
facility: Maine Medical Center- Scarborough Campus
state: Maine
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Bel Air
country: United States
facility: UM Upper Chesapeake Medical Center
state: Maryland
city: Columbia
country: United States
facility: Central Maryland Radiation Oncology in Howard County
state: Maryland
city: Glen Burnie
country: United States
facility: UM Baltimore Washington Medical Center/Tate Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Trinity Health Saint Joseph Mercy Hospital Ann Arbor
state: Michigan
city: Brownstown
country: United States
facility: Henry Ford Cancer Institute-Downriver
state: Michigan
city: Clarkston
country: United States
facility: Michigan Healthcare Professionals Clarkston
state: Michigan
city: Clinton Township
country: United States
facility: Henry Ford Macomb Hospital-Clinton Township
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Farmington Hills
country: United States
facility: Michigan Healthcare Professionals Farmington
state: Michigan
city: Livonia
country: United States
facility: Trinity Health Saint Mary Mercy Livonia Hospital
state: Michigan
city: Pontiac
country: United States
facility: Trinity Health Saint Joseph Mercy Oakland Hospital
state: Michigan
city: Royal Oak
country: United States
facility: Corewell Health William Beaumont University Hospital
state: Michigan
city: Troy
country: United States
facility: Corewell Health Beaumont Troy Hospital
state: Michigan
city: Troy
country: United States
facility: Michigan Healthcare Professionals Troy
state: Michigan
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Creve Coeur
country: United States
facility: Siteman Cancer Center at West County Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center at Saint Peters Hospital
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
state: New Hampshire
city: Mount Holly
country: United States
facility: Virtua Memorial
state: New Jersey
city: Somerville
country: United States
facility: Robert Wood Johnson University Hospital Somerset
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Albuquerque
country: United States
facility: New Mexico Oncology Hematology Consultants
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: White Plains
country: United States
facility: Dickstein Cancer Treatment Center
state: New York
city: Sylvania
country: United States
facility: ProMedica Flower Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Coos Bay
country: United States
facility: Bay Area Hospital
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania/Abramson Cancer Center
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital
state: Pennsylvania
city: Boiling Springs
country: United States
facility: Prisma Health Cancer Institute - Spartanburg
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Faris
state: South Carolina
city: Greenville
country: United States
facility: Saint Francis Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Eastside
state: South Carolina
city: Greer
country: United States
facility: Prisma Health Cancer Institute - Greer
state: South Carolina
city: Seneca
country: United States
facility: Prisma Health Cancer Institute - Seneca
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: League City
country: United States
facility: UTMB Cancer Center at Victory Lakes
state: Texas
city: Logan
country: United States
facility: Logan Regional Hospital
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: Salt Lake City
country: United States
facility: Utah Cancer Specialists-Salt Lake City
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Saint Johnsbury
country: United States
facility: Dartmouth Cancer Center - North
state: Vermont
city: Seattle
country: United States
facility: FHCC South Lake Union
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
city: Grafton
country: United States
facility: Aurora Cancer Care-Grafton
state: Wisconsin
city: Green Bay
country: United States
facility: Aurora BayCare Medical Center
state: Wisconsin
city: Kenosha
country: United States
facility: Aurora Cancer Care-Kenosha South
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center - University Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Saint Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Sinai Medical Center
state: Wisconsin
city: Oshkosh
country: United States
facility: Vince Lombardi Cancer Clinic - Oshkosh
state: Wisconsin
city: Sheboygan
country: United States
facility: Vince Lombardi Cancer Clinic-Sheboygan
state: Wisconsin
city: Summit
country: United States
facility: Aurora Medical Center in Summit
state: Wisconsin
city: Two Rivers
country: United States
facility: Vince Lombardi Cancer Clinic-Two Rivers
state: Wisconsin
city: West Allis
country: United States
facility: Aurora West Allis Medical Center
state: Wisconsin
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital and Cancer Center-General Campus
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre- Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
Study officials:
affiliation: NRG Oncology
name: Libni Eapen
role: PRINCIPAL_INVESTIGATOR
References: