A Prospective Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery for Patients With High Grade Upper Tract Urothelial Carcinoma


Condition: Localized Urothelial Carcinoma of the Renal Pelvis and Ureter, Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter, Regional Urothelial Carcinoma of the Renal Pelvis and Ureter

Intervention:

  • Drug: Methotrexate
  • Drug: Vinblastine
  • Drug: Doxorubicin Hydrochloride
  • Drug: Cisplatin
  • Drug: Gemcitabine Hydrochloride
  • Drug: Carboplatin
  • Procedure: Therapeutic Conventional Surgery
  • Other: Laboratory Biomarker Analysis

Purpose: This phase II trial studies how well giving chemotherapy before surgery works in treating patients with aggressive upper urinary tract cancer. Drugs used in chemotherapy, such as methotrexate, vinblastine, doxorubicin hydrochloride, cisplatin, gemcitabine hydrochloride, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Removing the affected upper urinary tract by surgery is the recommended treatment for upper urinary tract cancer, but can cause loss of kidney function and prevent patients from being able to receive chemotherapy after surgery. Giving chemotherapy before surgery, when the kidneys are working at their maximum, may allow less tissue to be removed during surgery and may be more effective in treating patients with high grade upper urinary tract cancer.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02412670

Sponsor: ECOG-ACRIN Cancer Research Group

Primary Outcome Measures:

  • Measure: pCR rates
  • Time Frame: Up to 5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Recurrence-free survival
  • Time Frame: From the date of surgery to disease recurrence or death from any cause, assessed up to 5 years
  • Safety Issue:
  • Measure: Event-free survival
  • Time Frame: From registration to the earlier of recurrence, disease progression, new invasive primary cancer, or death from any cause, assessed up to 5 years
  • Safety Issue:
  • Measure: Bladder cancer-free survival
  • Time Frame: From the date of surgery to the earlier of a return of bladder cancer or death from any cause, assessed up to 5 years
  • Safety Issue:
  • Measure: Cancer-specific survival
  • Time Frame: From registration to death due to cancer, assessed up to 5 years
  • Safety Issue:
  • Measure: The proportion of patients with renal insufficiency (CrCl < 60 ml/min) post chemotherapy and post nephroureterectomy
  • Time Frame: Up to 60 days after completion of chemotherapy
  • Safety Issue:
  • Measure: The proportion of patients with renal function improvement (CrCl < 60 ml/min at baseline and CrCl >= 60 ml/min on study)
  • Time Frame: Up to 60 days after completion of chemotherapy
  • Safety Issue:
  • Measure: Distribution of changes in renal function post chemotherapy and post surgery
  • Time Frame: Baseline up to 60 days after completion of chemotherapy
  • Safety Issue:
  • Measure: Incidence of toxicities
  • Time Frame: Up to 30 days from date of surgery
  • Safety Issue:

Estimated Enrollment: 60

Study Start Date: April 2015

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients must have high grade upper tract urothelial carcinoma proven by one of the following:
  • Biopsy;
  • Urinary cytology with a 3-dimensional upper urinary tract mass on cross-sectional imaging; or
  • Urinary cytology and a mass visualized during upper urinary tract endoscopy
  • Patients must have a creatinine clearance >= 30 ml/min as determined by Cockcroft-Gault calculation or 24-hour urine creatinine clearance measurement within 28 days of registration to be eligible for the study
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Patients must have no evidence of metastatic disease or clinically enlarged lymph nodes on computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis and CT chest obtained within 28 days of registration (a negative biopsy is required for lymph nodes > 1 cm in size to confirm lack of involvement); patients with lymph nodes > 1 cm in whom a biopsy is deemed not feasible are not eligible; patients with elevated alkaline phosphatase or suspicious bone pain should also undergo baseline bone scans to evaluate for bone metastasis
  • Patients with any component of small cell carcinoma are not eligible; other variant histologies are permitted provided the predominant (>= 50%) subtype is urothelial carcinoma
  • Patients must not have peripheral neuropathy > grade 2
  • Patients must not have a history of allergy or hypersensitivity to methotrexate, vinblastine, doxorubicin (doxorubicin hydrochloride), cisplatin, gemcitabine (gemcitabine hydrochloride), carboplatin or filgrastim or pegfilgrastim
  • Patients must have a left ventricular ejection fraction (LVEF) >= 50% by (either multigated acquisition [MUGA] or 2-dimensional [2-D] echocardiogram) within 28 days of registration
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelets >= 100,000/mm^3
  • Hemoglobin (HgB) >= 9
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2 X institutional upper limit of normal (ULN)
  • Bilirubin within institutional normal limits (or < 2.5 X the ULN for patients with Gilbert's disease)
  • Patients with concomitant primaries of the bladder/urethra are allowed, as long as these sites are surgically resected and non-invasive cancers (< cT1N0)
  • Patients must not have another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer; patients that have completed all necessary therapy and are considered to be at less than 30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment
  • For patients who have creatinine clearance that meets >= 50 ml/min they must not have received prior systemic doxorubicin
  • Patients with uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction in last 3 months, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible
  • Patients who are known to have human immunodeficiency virus (HIV) or are on combination antiretroviral therapy are ineligible
  • Patients must have no prior radiation therapy to >= 25% of the bone marrow for other diseases or prior systemic anthracycline therapy; prior intravesical anthracycline therapy for non-muscle invasive urothelial carcinoma of the bladder is permitted
  • Patients may have a history of resectable urothelial cancer (including neoadjuvant chemotherapy) as long as patients meet one of the following:
  • pT0, Tis, or T1N0 and have no evidence of disease (NED) for more than 2 years from surgery or chemotherapy;
  • pT2-3aN0 and NED for more than 3 years from surgery or chemotherapy; or
  • > pT3b, or N+ and NED for more than 5 years from surgery or chemotherapy
  • Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Women of childbearing potential and sexually active males must use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study

Locations:

  • University of Alabama at Birmingham Cancer Center
  • Birmingham Alabama 35233 United States
  • University of Colorado Cancer Center - Anschutz Cancer Pavilion
  • Aurora Colorado 80045 United States
  • Memorial Hospital Colorado Springs
  • Colorado Springs Colorado 80909 United States
  • Poudre Valley Hospital
  • Fort Collins Colorado 80524 United States
  • Saint Francis Hospital and Medical Center
  • Hartford Connecticut 06105 United States
  • Beebe Medical Center
  • Lewes Delaware 19958 United States
  • Christiana Gynecologic Oncology LLC
  • Newark Delaware 19713 United States
  • Delaware Clinical and Laboratory Physicians PA
  • Newark Delaware 19713 United States
  • Helen F Graham Cancer Center
  • Newark Delaware 19713 United States
  • Medical Oncology Hematology Consultants PA
  • Newark Delaware 19713 United States
  • Regional Hematology and Oncology PA
  • Newark Delaware 19713 United States
  • Christiana Care Health System-Christiana Hospital
  • Newark Delaware 19718 United States
  • Beebe Health Campus
  • Rehoboth Beach Delaware 19971 United States
  • Nanticoke Memorial Hospital
  • Seaford Delaware 19973 United States
  • Christiana Care Health System-Wilmington Hospital
  • Wilmington Delaware 19801 United States
  • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Savannah Georgia 31405 United States
  • Low Country Cancer Care Associates PC
  • Savannah Georgia 31405 United States
  • Saint Alphonsus Cancer Care Center-Boise
  • Boise Idaho 83706 United States
  • Saint Joseph Medical Center
  • Bloomington Illinois 61701 United States
  • Illinois CancerCare-Bloomington
  • Bloomington Illinois 61704 United States
  • Illinois CancerCare-Canton
  • Canton Illinois 61520 United States
  • Memorial Hospital of Carbondale
  • Carbondale Illinois 62902 United States
  • Illinois CancerCare-Carthage
  • Carthage Illinois 62321 United States
  • Centralia Oncology Clinic
  • Centralia Illinois 62801 United States
  • Carle on Vermilion
  • Danville Illinois 61832 United States
  • Cancer Care Center of Decatur
  • Decatur Illinois 62526 United States
  • Decatur Memorial Hospital
  • Decatur Illinois 62526 United States
  • Carle Physician Group-Effingham
  • Effingham Illinois 62401 United States
  • Crossroads Cancer Center
  • Effingham Illinois 62401 United States
  • Illinois CancerCare-Eureka
  • Eureka Illinois 61530 United States
  • Illinois CancerCare Galesburg
  • Galesburg Illinois 61401 United States
  • Western Illinois Cancer Treatment Center
  • Galesburg Illinois 61401 United States
  • Illinois CancerCare-Kewanee Clinic
  • Kewanee Illinois 61443 United States
  • Illinois CancerCare-Macomb
  • Macomb Illinois 61455 United States
  • Carle Physician Group-Mattoon/Charleston
  • Mattoon Illinois 61938 United States
  • Good Samaritan Regional Health Center
  • Mount Vernon Illinois 62864 United States
  • Illinois CancerCare-Ottawa Clinic
  • Ottawa Illinois 61350 United States
  • Radiation Oncology of Northern Illinois
  • Ottawa Illinois 61350 United States
  • Illinois CancerCare-Pekin
  • Pekin Illinois 61554 United States
  • Pekin Cancer Treatment Center
  • Pekin Illinois 61554 United States
  • Methodist Medical Center of Illinois
  • Peoria Illinois 61603 United States
  • OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC
  • Peoria Illinois 61615-7827 United States
  • Illinois CancerCare-Peoria
  • Peoria Illinois 61615 United States
  • OSF Saint Francis Medical Center
  • Peoria Illinois 61637 United States
  • Illinois CancerCare-Peru
  • Peru Illinois 61354 United States
  • Valley Radiation Oncology
  • Peru Illinois 61354 United States
  • Illinois CancerCare-Princeton
  • Princeton Illinois 61356 United States
  • Central Illinois Hematology Oncology Center
  • Springfield Illinois 62702 United States
  • Southern Illinois University School of Medicine
  • Springfield Illinois 62702 United States
  • Springfield Clinic
  • Springfield Illinois 62703 United States
  • Memorial Medical Center
  • Springfield Illinois 62781 United States
  • Cancer Care Specialists of Illinois-Swansea
  • Swansea Illinois 62226 United States
  • Carle Cancer Center
  • Urbana Illinois 61801 United States
  • The Carle Foundation Hospital
  • Urbana Illinois 61801 United States
  • Franciscan Saint Anthony Health-Michigan City
  • Michigan City Indiana 46360 United States
  • Woodland Cancer Care Center
  • Michigan City Indiana 46360 United States
  • Reid Hospital and Health Care Services
  • Richmond Indiana 47374 United States
  • Oncology Hematology Care Inc-Crestview
  • Crestview Hills Kentucky 41017 United States
  • Ochsner Medical Center Jefferson
  • New Orleans Louisiana 70121 United States
  • Saint Joseph Mercy Hospital
  • Ann Arbor Michigan 48106-0995 United States
  • University of Michigan Comprehensive Cancer Center
  • Ann Arbor Michigan 48109 United States
  • Oakwood Hospital and Medical Center
  • Dearborn Michigan 48124 United States
  • Saint John Hospital and Medical Center
  • Detroit Michigan 48236 United States
  • Hurley Medical Center
  • Flint Michigan 48502 United States
  • Genesys Hurley Cancer Institute
  • Flint Michigan 48503 United States
  • Allegiance Health
  • Jackson Michigan 49201 United States
  • Sparrow Hospital
  • Lansing Michigan 48912 United States
  • Saint Mary Mercy Hospital
  • Livonia Michigan 48154 United States
  • Saint Joseph Mercy Oakland
  • Pontiac Michigan 48341 United States
  • Saint Joseph Mercy Port Huron
  • Port Huron Michigan 48060 United States
  • Saint Mary's of Michigan
  • Saginaw Michigan 48601 United States
  • Saint John Macomb-Oakland Hospital
  • Warren Michigan 48093 United States
  • Central Care Cancer Center-Carrie J Babb Cancer Center
  • Bolivar Missouri 65613 United States
  • Parkland Health Center-Bonne Terre
  • Bonne Terre Missouri 63628 United States
  • CoxHealth Cancer Center
  • Branson Missouri 65616 United States
  • Saint Francis Medical Center
  • Cape Girardeau Missouri 63703 United States
  • Southeast Cancer Center
  • Cape Girardeau Missouri 63703 United States
  • Capital Region Medical Center-Goldschmidt Cancer Center
  • Jefferson City Missouri 65109 United States
  • Freeman Health System
  • Joplin Missouri 64804 United States
  • Mercy Hospital-Joplin
  • Joplin Missouri 64804 United States
  • Phelps County Regional Medical Center
  • Rolla Missouri 65401 United States
  • Saint John's Clinic-Rolla-Cancer and Hematology
  • Rolla Missouri 65401 United States
  • Saint Louis Cancer and Breast Institute-South City
  • Saint Louis Missouri 63109 United States
  • Missouri Baptist Medical Center
  • Saint Louis Missouri 63131 United States
  • Mercy Hospital Saint Louis
  • Saint Louis Missouri 63141 United States
  • Sainte Genevieve County Memorial Hospital
  • Sainte Genevieve Missouri 63670 United States
  • Mercy Hospital Springfield
  • Springfield Missouri 65804 United States
  • CoxHealth South Hospital
  • Springfield Missouri 65807 United States
  • Missouri Baptist Sullivan Hospital
  • Sullivan Missouri 63080 United States
  • Missouri Baptist Outpatient Center-Sunset Hills
  • Sunset Hills Missouri 63127 United States
  • Miami Valley Hospital South
  • Centerville Ohio 45459 United States
  • Oncology Hematology Care Inc-Eden Park
  • Cincinnati Ohio 45202 United States
  • Oncology Hematology Care Inc-Mercy West
  • Cincinnati Ohio 45211 United States
  • Oncology Hematology Care Inc - Anderson
  • Cincinnati Ohio 45230 United States
  • Oncology Hematology Care Inc - Kenwood
  • Cincinnati Ohio 45236 United States
  • Oncology Hematology Care Inc-Blue Ash
  • Cincinnati Ohio 45242 United States
  • Good Samaritan Hospital - Dayton
  • Dayton Ohio 45406 United States
  • Miami Valley Hospital
  • Dayton Ohio 45409 United States
  • Samaritan North Health Center
  • Dayton Ohio 45415 United States
  • Oncology Hematology Care Inc-Healthplex
  • Fairfield Ohio 45014 United States
  • Blanchard Valley Hospital
  • Findlay Ohio 45840 United States
  • Atrium Medical Center-Middletown Regional Hospital
  • Franklin Ohio 45005-1066 United States
  • Wayne Hospital
  • Greenville Ohio 45331 United States
  • Kettering Medical Center
  • Kettering Ohio 45429 United States
  • Springfield Regional Cancer Center
  • Springfield Ohio 45504 United States
  • Springfield Regional Medical Center
  • Springfield Ohio 45505 United States
  • Flower Hospital
  • Sylvania Ohio 43560 United States
  • Upper Valley Medical Center
  • Troy Ohio 45373 United States
  • University of Oklahoma Health Sciences Center
  • Oklahoma City Oklahoma 73104 United States
  • Tulsa Cancer Institute
  • Tulsa Oklahoma 74146 United States
  • Christiana Care Health System-Concord Health Center
  • Chadds Ford Pennsylvania 19317 United States
  • Geisinger Medical Center
  • Danville Pennsylvania 17822 United States
  • Geisinger Medical Center-Cancer Center Hazleton
  • Hazleton Pennsylvania 18201 United States
  • Geisinger Medical Oncology at Evangelical Community Hospital
  • Lewisburg Pennsylvania 17837 United States
  • Lewistown Hospital
  • Lewistown Pennsylvania 17044 United States
  • ECOG-ACRIN Cancer Research Group
  • Philadelphia Pennsylvania 19103 United States
  • Thomas Jefferson University Hospital
  • Philadelphia Pennsylvania 19107 United States
  • Geisinger Medical Oncology-Pottsville
  • Pottsville Pennsylvania 17901 United States
  • Geisinger Medical Group
  • State College Pennsylvania 16801 United States
  • Geisinger Wyoming Valley/Henry Cancer Center
  • Wilkes-Barre Pennsylvania 18711 United States
  • Medical University of South Carolina
  • Charleston South Carolina 29425 United States
  • Vanderbilt-Ingram Cancer Center Cool Springs
  • Franklin Tennessee 37067 United States
  • Vanderbilt Breast Center at One Hundred Oaks
  • Nashville Tennessee 37204 United States
  • Vanderbilt University/Ingram Cancer Center
  • Nashville Tennessee 37232 United States
  • UT Southwestern/Simmons Cancer Center-Dallas
  • Dallas Texas 75390 United States
  • Aurora Cancer Care-Burlington
  • Burlington Wisconsin 53105 United States
  • Aurora Cancer Care-Grafton
  • Grafton Wisconsin 53024 United States
  • Vince Lombardi Cancer Clinic-Marinette
  • Marinette Wisconsin 54143 United States
  • Aurora Advanced Healthcare Inc-Menomonee Falls
  • Menomonee Falls Wisconsin 53051 United States
  • Aurora Cancer Care-Milwaukee
  • Milwaukee Wisconsin 53209 United States
  • Vince Lombardi Cancer Clinic - Oshkosh
  • Oshkosh Wisconsin 54904 United States
  • Aurora Cancer Care-Racine
  • Racine Wisconsin 53406-5661 United States
  • Aurora Medical Center in Summit
  • Summit Wisconsin 53066 United States
  • Aurora Cancer Care-Waukesha
  • Waukesha Wisconsin 53188 United States

View trial on ClinicalTrials.gov