Bladder Cancer Clinical Trial

Chemotherapy Before Surgery in Treating Patients With High Grade Upper Urinary Tract Cancer

Summary

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.

View Full Description

Full Description

PRIMARY OBJECTIVES:

I. To evaluate the rate of complete pathologic response (pCR = pT0pN0) as assessed by standard pathologic review attained by neoadjuvant systemic chemotherapy and nephroureterectomy.

SECONDARY OBJECTIVES:

I. To evaluate the safety of neoadjuvant systemic chemotherapy in patients with upper tract urothelial carcinoma preceding nephroureterectomy.

II. To evaluate distant recurrence-free survival of patients treated with neoadjuvant systemic chemotherapy preceding nephroureterectomy.

III. To evaluate event-free survival of patients treated with neoadjuvant systemic chemotherapy preceding nephroureterectomy.

IV. To evaluate bladder cancer-free survival of patients treated with neoadjuvant systemic chemotherapy preceding nephroureterectomy.

V. To evaluate cancer specific survival of patients treated with neoadjuvant systemic chemotherapy preceding nephroureterectomy.

VI. To evaluate renal functional outcomes of patients treated with neoadjuvant systemic chemotherapy preceding nephroureterectomy.

TERTIARY OBJECTIVES:

I. To collect pre-treatment and post-treatment tumor tissue, peripheral blood mononuclear cell (PBMC), peripheral blood plasma, and urine specimens for potential evaluations of markers of chemotherapy response/resistance.

OUTLINE: Patients are assigned to 1 of 2 treatment arms based on baseline renal function.

ARM A (CREATININE CLEARANCE [CRCL] > 50): Patients receive methotrexate intravenously (IV) over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.

ARM B (30 =< CRCL <= 50): Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

View Eligibility Criteria

Eligibility Criteria

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 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 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 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

Exclusion Criteria:

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
Any component of small cell carcinoma; other variant histologies are permitted provided the predominant (>= 50%) subtype is urothelial carcinoma
Peripheral neuropathy > grade 2
History of allergy or hypersensitivity to methotrexate, vinblastine, doxorubicin (doxorubicin hydrochloride), cisplatin, gemcitabine (gemcitabine hydrochloride), carboplatin or filgrastim or pegfilgrastim
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
Prior systemic doxorubicin for patients who have creatinine clearance that meets >= 50 ml/min
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
Known to have human immunodeficiency virus (HIV) or are on combination antiretroviral therapy
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
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)

Study is for people with:

Bladder Cancer

Phase:

Phase 2

Estimated Enrollment:

36

Study ID:

NCT02412670

Recruitment Status:

Completed

Sponsor:

ECOG-ACRIN Cancer Research Group

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There are 116 Locations for this study

See Locations Near You

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, 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, 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, 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, United States
Aurora Medical Center in Summit
Summit Wisconsin, 53066, United States
Aurora Cancer Care-Waukesha
Waukesha Wisconsin, 53188, United States

How clear is this clinincal trial information?

Study is for people with:

Bladder Cancer

Phase:

Phase 2

Estimated Enrollment:

36

Study ID:

NCT02412670

Recruitment Status:

Completed

Sponsor:


ECOG-ACRIN Cancer Research Group

How clear is this clinincal trial information?

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