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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02316548
Other study ID # NRG-GU001
Secondary ID NCI-2014-02061NR
Status Terminated
Phase Phase 2
First received
Last updated
Start date February 2015
Est. completion date February 1, 2017

Study information

Verified date March 2018
Source NRG Oncology
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 14
Est. completion date February 1, 2017
Est. primary completion date February 1, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

Radiation:
Intensity-Modulated Radiation Therapy
Postoperative adjuvant IMRT radiotherapy 50.4 Gy in 28 fractions. In patients not getting postoperative adjuvant chemotherapy the radiation treatment must begin within 140 days after cystectomy. For patients getting adjuvant chemotherapy radiation treatment must start within 49 days of completing chemotherapy.

Locations

Country Name City State
Canada Tom Baker Cancer Centre Calgary Alberta
Canada Juravinski Cancer Centre at Hamilton Health Sciences Hamilton Ontario
Canada London Regional Cancer Program London Ontario
Canada CHUM - Hopital Notre-Dame Montreal Quebec
Canada Jewish General Hospital Montreal Quebec
Canada McGill University Department of Oncology Montreal Quebec
Canada Ottawa Hospital and Cancer Center-General Campus Ottawa Ontario
Canada Allan Blair Cancer Centre Regina Saskatchewan
Canada Saskatoon Cancer Centre Saskatoon Saskatchewan
Canada Odette Cancer Centre- Sunnybrook Health Sciences Centre Toronto Ontario
Israel Rabin Medical Center Petach Tikva
United States New Mexico Oncology Hematology Consultants Albuquerque New Mexico
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States McFarland Clinic PC-William R Bliss Cancer Center Ames Iowa
United States Saint Joseph Mercy Hospital Ann Arbor Michigan
United States Emory Saint Joseph's Hospital Atlanta Georgia
United States Emory University Hospital Midtown Atlanta Georgia
United States Emory University Hospital/Winship Cancer Institute Atlanta Georgia
United States University of Colorado Hospital Aurora Colorado
United States AIS Cancer Center at San Joaquin Community Hospital Bakersfield California
United States University of Maryland/Greenebaum Cancer Center Baltimore Maryland
United States Upper Chesapeake Medical Center Bel Air Maryland
United States Billings Clinic Cancer Center Billings Montana
United States Saint Luke's Mountain States Tumor Institute Boise Idaho
United States Massachusetts General Hospital Cancer Center Boston Massachusetts
United States Henry Ford Cancer Institute?Downriver Brownstown Michigan
United States Roswell Park Cancer Institute Buffalo New York
United States Lahey Hospital and Medical Center Burlington Massachusetts
United States Medical University of South Carolina Charleston South Carolina
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States 21st Century Oncology-Clarkston Clarkston Michigan
United States Henry Ford Macomb Hospital-Clinton Township Clinton Township Michigan
United States Memorial Hospital Central Colorado Springs Colorado
United States Penrose-Saint Francis Healthcare Colorado Springs Colorado
United States Central Maryland Radiation Oncology in Howard County Columbia Maryland
United States Bay Area Hospital Coos Bay Oregon
United States Siteman Cancer Center at West County Hospital Creve Coeur Missouri
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Decatur Memorial Hospital Decatur Illinois
United States Henry Ford Hospital Detroit Michigan
United States 21st Century Oncology-Farmington Hills Farmington Hills Michigan
United States Poudre Valley Hospital Fort Collins Colorado
United States Parkview Hospital Randallia Fort Wayne Indiana
United States Radiation Oncology Associates PC Fort Wayne Indiana
United States Saint Luke's Mountain States Tumor Institute - Fruitland Fruitland Idaho
United States Northeast Georgia Medical Center-Gainesville Gainesville Georgia
United States University of Texas Medical Branch Galveston Texas
United States Tate Cancer Center Glen Burnie Maryland
United States Goshen Center for Cancer Care Goshen Indiana
United States Aurora Cancer Care-Grafton Grafton Wisconsin
United States Aurora BayCare Medical Center Green Bay Wisconsin
United States Marin General Hospital Greenbrae California
United States Greenville Health System Cancer Institute-Eastside Greenville South Carolina
United States Greenville Health System Cancer Institute-Faris Greenville South Carolina
United States Saint Francis Cancer Center Greenville South Carolina
United States Greenville Health System Cancer Institute-Greer Greer South Carolina
United States University of Mississippi Medical Center Jackson Mississippi
United States University of Kansas Cancer Center Kansas City Kansas
United States Aurora Cancer Care-Kenosha South Kenosha Wisconsin
United States Lawrence Memorial Hospital Lawrence Kansas
United States UTMB Cancer Center at Victory Lakes League City Texas
United States Dartmouth Hitchcock Medical Center Lebanon New Hampshire
United States Saint Mary Mercy Hospital Livonia Michigan
United States Logan Regional Hospital Logan Utah
United States Los Angeles County-USC Medical Center Los Angeles California
United States USC / Norris Comprehensive Cancer Center Los Angeles California
United States Jewish Hospital Medical Center Northeast Louisville Kentucky
United States Norton Hospital Pavilion and Medical Campus Louisville Kentucky
United States University of Wisconsin Hospital and Clinics Madison Wisconsin
United States Loyola University Medical Center Maywood Illinois
United States Saint Luke's Mountain States Tumor Institute - Meridian Meridian Idaho
United States Aurora Saint Luke's Medical Center Milwaukee Wisconsin
United States Aurora Sinai Medical Center Milwaukee Wisconsin
United States Froedtert and the Medical College of Wisconsin Milwaukee Wisconsin
United States Memorial Regional Cancer Center Day Road Mishawaka Indiana
United States West Virginia University Healthcare Morgantown West Virginia
United States Virtua Memorial Mount Holly New Jersey
United States Intermountain Medical Center Murray Utah
United States Saint Luke's Mountain States Tumor Institute - Nampa Nampa Idaho
United States Vanderbilt University/Ingram Cancer Center Nashville Tennessee
United States Christiana Care Health System-Christiana Hospital Newark Delaware
United States McKay-Dee Hospital Center Ogden Utah
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Nebraska Methodist Hospital Omaha Nebraska
United States Vince Lombardi Cancer Clinic - Oshkosh Oshkosh Wisconsin
United States Stanford Cancer Institute Palo Alto Palo Alto California
United States OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center Pekin Illinois
United States OSF Saint Francis Medical Center Peoria Illinois
United States OSF Saint Francis Radiation Oncology at Peoria Cancer Center Peoria Illinois
United States NRG Oncology Philadelphia Pennsylvania
United States University of Pennsylvania/Abramson Cancer Center Philadelphia Pennsylvania
United States Saint Joseph Mercy Oakland Pontiac Michigan
United States Beebe Health Campus Rehoboth Beach Delaware
United States Renown Regional Medical Center Reno Nevada
United States University of Rochester Rochester New York
United States William Beaumont Hospital-Royal Oak Royal Oak Michigan
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States Norris Cotton Cancer Center-North Saint Johnsbury Vermont
United States Missouri Baptist Medical Center Saint Louis Missouri
United States Washington University School of Medicine Saint Louis Missouri
United States Regions Hospital Saint Paul Minnesota
United States Siteman Cancer Center at Saint Peters Hospital Saint Peters Missouri
United States Huntsman Cancer Institute/University of Utah Salt Lake City Utah
United States Utah Cancer Specialists-Salt Lake City Salt Lake City Utah
United States Lewis Cancer and Research Pavilion at Saint Joseph's/Candler Savannah Georgia
United States Maine Medical Center- Scarborough Campus Scarborough Maine
United States Seattle Cancer Care Alliance Seattle Washington
United States University of Washington Medical Center Seattle Washington
United States Greenville Health System Cancer Institute-Seneca Seneca South Carolina
United States Vince Lombardi Cancer Clinic-Sheboygan Sheboygan Wisconsin
United States Robert Wood Johnson University Hospital Somerset Somerville New Jersey
United States Memorial Hospital of South Bend South Bend Indiana
United States Greenville Health System Cancer Institute-Spartanburg Spartanburg South Carolina
United States Spartanburg Medical Center Spartanburg South Carolina
United States Memorial Medical Center Springfield Illinois
United States Stony Brook University Medical Center Stony Brook New York
United States Aurora Medical Center in Summit Summit Wisconsin
United States Flower Hospital Sylvania Ohio
United States Moffitt Cancer Center Tampa Florida
United States 21st Century Oncology-Troy Troy Michigan
United States William Beaumont Hospital - Troy Troy Michigan
United States Saint Luke's Mountain States Tumor Institute-Twin Falls Twin Falls Idaho
United States Vince Lombardi Cancer Clinic-Two Rivers Two Rivers Wisconsin
United States Carle Cancer Center Urbana Illinois
United States Aurora West Allis Medical Center West Allis Wisconsin
United States Reading Hospital West Reading Pennsylvania
United States Dickstein Cancer Treatment Center White Plains New York
United States Via Christi Regional Medical Center Wichita Kansas

Sponsors (2)

Lead Sponsor Collaborator
NRG Oncology National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Israel, 

Outcome

Type Measure Description Time frame Safety issue
Primary Pelvic Recurrence-free Survival (PRFS) PRFS is defined as time free of pelvic recurrence or death, with patients who experience distant metastasis censored at the time of occurrence. Pelvic recurrence is specifically defined as soft tissue and /or lymph node tumor recurrence in the pelvis anywhere between the L5-S1 disc space superiorly and the pelvic floor inferiorly. This was to be determined on the basis of pelvic imaging (CT or MRI scan demonstrating soft tissue or nodal recurrence at least 1cm in linear dimension) or urethroscopy; biopsy was not required. PRFS was to be tested between arms in terms of a difference in cause-specific-hazards using the log-rank test and cumulative incidence of PRFS in the presence of competing risks was to be computed via cumulative incidence. Due to early termination with few patients, only counts of events have been calculated. From randomization to study termination, maximum follow-up was 13.3 months, median follow-up was 1.9 months
Secondary Disease Free Survival (DFS) Disease free survival (DFS) is defined as the first occurrence of either: pelvic failure, distant metastasis, or death and was to be estimated by the Kaplan-Meier method and arms compared using the log-rank test. Pelvic recurrence is specifically defined as soft tissue and /or lymph node tumor recurrence in the pelvis anywhere between the L5-S1 disc space superiorly and the pelvic floor inferiorly. This was to be determined on the basis of pelvic imaging (CT or MRI scan demonstrating soft tissue or nodal recurrence at least 1cm in linear dimension) or urethroscopy; biopsy was not required. Distant metastases is defined as any hematogenous metastases and/or lymph node metastases above the L5-S1 interspace, documented by imaging (CT and/or MRI and/or bone scans). Due to early termination with few patients, only counts of events have been calculated. From randomization to study termination, maximum follow-up was 13.3 months, median follow-up was 1.9 months
Secondary Number of Patients With Bowel Toxicity Adverse events (AE) evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Bowel toxicity= abdominal distension/pain, colitis, colonic fistula/ hemorrhage/obstruction/perforation/stenosis/ulcer, diarrhea, enterocolitis, fecal incontinence/gastrointestinal/fistula/pain, ileal fistula/hemorrhage/obstruction/perforation/stenosis/ulcer, Ileus, jejunal fistula/hemorrhage/obstruction/perforation/stenosis/ulcer, lower gastrointestinal hemorrhage, rectal fistula/hemorrhage/mucositis/necrosis/obstruction/pain/perforation/stenosis/ulcer, small intestinal mucositis/obstruction/perforation/stenosis/ulcer, vomiting. Highest grade adverse event per subject counted. Grade refers to AE severity and ranges from 1 to 5 with unique clinical descriptions of severity for each AE based on this general guideline: 1 Mild, 2 Moderate, 3 Severe, 4 Life-threatening or disabling, 5 Death related to AE. From randomization to study termination, maximum follow-up was 13.3 months, median follow-up was 1.9 months
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