Surgery With or Without Postoperative Intensity Modulated Radiation Therapy in Treating Patients With Urothelial Bladder Cancer

Stage IV Bladder Cancer Clinical Trial

Official title:

Randomized Phase II Trial of Postoperative Adjuvant IMRT Following Cystectomy for pT3/T4 Urothelial Bladder Cancer

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
• 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
• 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

Related Conditions & MeSH terms

• Stage III Bladder Cancer
• Stage IV Bladder Cancer
• Urinary Bladder Neoplasms

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