search
Back to results

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

Primary Purpose

High Grade Upper Tract Urothelial Carcinoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Methotrexate
Vinblastine
Doxorubicin
Cisplatin
Gemcitabine
Carboplatin
Pegfilgrastim
Nephroureterectomy
Sponsored by
ECOG-ACRIN Cancer Research Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for High Grade Upper Tract Urothelial Carcinoma focused on measuring carcinoma, drug therapy, nephroureterectomy, urinary tract, urothelium

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University of Alabama at Birmingham Cancer Center
  • University of Colorado Cancer Center - Anschutz Cancer Pavilion
  • Memorial Hospital Colorado Springs
  • Poudre Valley Hospital
  • Saint Francis Hospital and Medical Center
  • Beebe Medical Center
  • Christiana Gynecologic Oncology LLC
  • Delaware Clinical and Laboratory Physicians PA
  • Helen F Graham Cancer Center
  • Medical Oncology Hematology Consultants PA
  • Regional Hematology and Oncology PA
  • Christiana Care Health System-Christiana Hospital
  • Beebe Health Campus
  • Nanticoke Memorial Hospital
  • Christiana Care Health System-Wilmington Hospital
  • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
  • Low Country Cancer Care Associates PC
  • Saint Alphonsus Cancer Care Center-Boise
  • Saint Joseph Medical Center
  • Illinois CancerCare-Bloomington
  • Illinois CancerCare-Canton
  • Memorial Hospital of Carbondale
  • Illinois CancerCare-Carthage
  • Centralia Oncology Clinic
  • Carle on Vermilion
  • Cancer Care Center of Decatur
  • Decatur Memorial Hospital
  • Carle Physician Group-Effingham
  • Crossroads Cancer Center
  • Illinois CancerCare-Eureka
  • Illinois CancerCare Galesburg
  • Western Illinois Cancer Treatment Center
  • Illinois CancerCare-Kewanee Clinic
  • Illinois CancerCare-Macomb
  • Carle Physician Group-Mattoon/Charleston
  • Good Samaritan Regional Health Center
  • Illinois CancerCare-Ottawa Clinic
  • Radiation Oncology of Northern Illinois
  • Illinois CancerCare-Pekin
  • Pekin Cancer Treatment Center
  • Methodist Medical Center of Illinois
  • OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC
  • Illinois CancerCare-Peoria
  • OSF Saint Francis Medical Center
  • Illinois CancerCare-Peru
  • Valley Radiation Oncology
  • Illinois CancerCare-Princeton
  • Central Illinois Hematology Oncology Center
  • Southern Illinois University School of Medicine
  • Springfield Clinic
  • Memorial Medical Center
  • Cancer Care Specialists of Illinois-Swansea
  • Carle Cancer Center
  • The Carle Foundation Hospital
  • Franciscan Saint Anthony Health-Michigan City
  • Woodland Cancer Care Center
  • Reid Hospital and Health Care Services
  • Oncology Hematology Care Inc-Crestview
  • Ochsner Medical Center Jefferson
  • Saint Joseph Mercy Hospital
  • University of Michigan Comprehensive Cancer Center
  • Oakwood Hospital and Medical Center
  • Saint John Hospital and Medical Center
  • Hurley Medical Center
  • Genesys Hurley Cancer Institute
  • Allegiance Health
  • Sparrow Hospital
  • Saint Mary Mercy Hospital
  • Saint Joseph Mercy Oakland
  • Saint Joseph Mercy Port Huron
  • Saint Mary's of Michigan
  • Saint John Macomb-Oakland Hospital
  • Central Care Cancer Center-Carrie J Babb Cancer Center
  • Parkland Health Center-Bonne Terre
  • CoxHealth Cancer Center
  • Saint Francis Medical Center
  • Southeast Cancer Center
  • Capital Region Medical Center-Goldschmidt Cancer Center
  • Freeman Health System
  • Mercy Hospital-Joplin
  • Phelps County Regional Medical Center
  • Saint John's Clinic-Rolla-Cancer and Hematology
  • Saint Louis Cancer and Breast Institute-South City
  • Missouri Baptist Medical Center
  • Mercy Hospital Saint Louis
  • Sainte Genevieve County Memorial Hospital
  • Mercy Hospital Springfield
  • CoxHealth South Hospital
  • Missouri Baptist Sullivan Hospital
  • Missouri Baptist Outpatient Center-Sunset Hills
  • Miami Valley Hospital South
  • Oncology Hematology Care Inc-Eden Park
  • Oncology Hematology Care Inc-Mercy West
  • Oncology Hematology Care Inc - Anderson
  • Oncology Hematology Care Inc - Kenwood
  • Oncology Hematology Care Inc-Blue Ash
  • Good Samaritan Hospital - Dayton
  • Miami Valley Hospital
  • Samaritan North Health Center
  • Oncology Hematology Care Inc-Healthplex
  • Blanchard Valley Hospital
  • Atrium Medical Center-Middletown Regional Hospital
  • Wayne Hospital
  • Kettering Medical Center
  • Springfield Regional Cancer Center
  • Springfield Regional Medical Center
  • Flower Hospital
  • Upper Valley Medical Center
  • University of Oklahoma Health Sciences Center
  • Tulsa Cancer Institute
  • Christiana Care Health System-Concord Health Center
  • Geisinger Medical Center
  • Geisinger Medical Center-Cancer Center Hazleton
  • Geisinger Medical Oncology at Evangelical Community Hospital
  • Lewistown Hospital
  • ECOG-ACRIN Cancer Research Group
  • Thomas Jefferson University Hospital
  • Geisinger Medical Oncology-Pottsville
  • Geisinger Medical Group
  • Geisinger Wyoming Valley/Henry Cancer Center
  • Medical University of South Carolina
  • Vanderbilt-Ingram Cancer Center Cool Springs
  • Vanderbilt Breast Center at One Hundred Oaks
  • Vanderbilt University/Ingram Cancer Center
  • UT Southwestern/Simmons Cancer Center-Dallas
  • Aurora Cancer Care-Burlington
  • Aurora Cancer Care-Grafton
  • Vince Lombardi Cancer Clinic-Marinette
  • Aurora Advanced Healthcare Inc-Menomonee Falls
  • Aurora Cancer Care-Milwaukee
  • Vince Lombardi Cancer Clinic - Oshkosh
  • Aurora Cancer Care-Racine
  • Aurora Medical Center in Summit
  • Aurora Cancer Care-Waukesha

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A (methotrexate, vinblastine, doxorubicin, cisplatin)

Arm B (gemcitabine, carboplatin)

Arm Description

Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. 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.

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.

Outcomes

Primary Outcome Measures

Complete Pathologic Response Rate
Complete pathologic response is defined as pT0pN0 (no evidence of disease) as assessed by pathologic evaluation of nephrectomy/ureterectomy and any identifiable regional lymph nodes.

Secondary Outcome Measures

Recurrence-free Survival
Recurrence-free survival is defined as the time from the date of surgery to disease recurrence or death from any cause. Patients alive without documented recurrence will be censored at the date of last disease assessment.
Event-free Survival
Event-free survival is defined as the time from registration to the earliest occurrence of recurrence of any type, disease progression, new invasive primary cancer, or death from any cause. Disease progression will be assessed using RECIST 1.1. Disease progression is defined as appearance of one or more new lesions, unequivocal progression of existing non-target lesions, or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Bladder Cancer-free Survival
Bladder cancer-free survival was defined as the time from the date of surgery to the earlier of a return of bladder cancer or death from any cause. Patients alive without documented bladder cancer were censored at the date of last disease assessment.
Cumulative Incidence of Cancer-specific Death at 24 Months
Cancer-specific survival was defined as the time from registration to death due to cancer; deaths due to other causes are counted as competing events. Cancer-specific survival was analyzed using Gray's method and cumulative incidence of cancer-specific death at 24 months is reported.
Proportion of Patients With Renal Insufficiency at Completion of Chemotherapy
Renal insufficiency is defined as CrCl < 60 ml/min.
Proportion of Patients With Renal Insufficiency at Completion of Surgery
Renal insufficiency is defined as CrCl < 60 ml/min.

Full Information

First Posted
April 6, 2015
Last Updated
June 21, 2023
Sponsor
ECOG-ACRIN Cancer Research Group
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT02412670
Brief Title
Chemotherapy Before Surgery in Treating Patients With High Grade Upper Urinary Tract Cancer
Official Title
A Prospective Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery for Patients With High Grade Upper Tract Urothelial Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
August 27, 2015 (Actual)
Primary Completion Date
August 23, 2018 (Actual)
Study Completion Date
May 10, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ECOG-ACRIN Cancer Research Group
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High Grade Upper Tract Urothelial Carcinoma
Keywords
carcinoma, drug therapy, nephroureterectomy, urinary tract, urothelium

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A (methotrexate, vinblastine, doxorubicin, cisplatin)
Arm Type
Experimental
Arm Description
Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. 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 Title
Arm B (gemcitabine, carboplatin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
Folex, abitrexate, mexate
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Vinblastine
Other Intervention Name(s)
vinblastine sulfate
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin R, Rubex R, Adriamycin RDF R, Adriamycin PFS R, hydroxydaunorubicin, hydroxydaunomycin, ADR
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Cisdiaminedichloroplatinum, Cis-diaminedichloroplatinum (II), diaminedichloroplatinum, cis-platinum, platinum, Platinol, Platinol-AQ, DDP, CDDP, DACP, NSC 119875
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
2'-Deoxy-2', 2'-difluorocytidine monohydrochloride, Gemzar
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Paraplatin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Pegfilgrastim
Other Intervention Name(s)
Neulasta
Intervention Description
Administered subcutaneously
Intervention Type
Procedure
Intervention Name(s)
Nephroureterectomy
Intervention Description
Undergo nephroureterectomy and lymph node dissection
Primary Outcome Measure Information:
Title
Complete Pathologic Response Rate
Description
Complete pathologic response is defined as pT0pN0 (no evidence of disease) as assessed by pathologic evaluation of nephrectomy/ureterectomy and any identifiable regional lymph nodes.
Time Frame
Assessed at nephroureterectomy or regional lymph node dissection (21-60 days from completion of chemotherapy; chemotherapy was administered for a total of 4 cycles; cycle length is 14 days and 21 days for arms A and B, respectively)
Secondary Outcome Measure Information:
Title
Recurrence-free Survival
Description
Recurrence-free survival is defined as the time from the date of surgery to disease recurrence or death from any cause. Patients alive without documented recurrence will be censored at the date of last disease assessment.
Time Frame
Assessed every 3 months for 2 years; and every 6 months for 3-5 years
Title
Event-free Survival
Description
Event-free survival is defined as the time from registration to the earliest occurrence of recurrence of any type, disease progression, new invasive primary cancer, or death from any cause. Disease progression will be assessed using RECIST 1.1. Disease progression is defined as appearance of one or more new lesions, unequivocal progression of existing non-target lesions, or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time Frame
Assessed every 3 months for 2 years, and every 6 months for 3-5 years
Title
Bladder Cancer-free Survival
Description
Bladder cancer-free survival was defined as the time from the date of surgery to the earlier of a return of bladder cancer or death from any cause. Patients alive without documented bladder cancer were censored at the date of last disease assessment.
Time Frame
Assessed every 3 months for 2 years, and every 6 months for 3-5 years
Title
Cumulative Incidence of Cancer-specific Death at 24 Months
Description
Cancer-specific survival was defined as the time from registration to death due to cancer; deaths due to other causes are counted as competing events. Cancer-specific survival was analyzed using Gray's method and cumulative incidence of cancer-specific death at 24 months is reported.
Time Frame
Assessed every 3 months for 2 years
Title
Proportion of Patients With Renal Insufficiency at Completion of Chemotherapy
Description
Renal insufficiency is defined as CrCl < 60 ml/min.
Time Frame
Assessed at completion of chemotherapy; at 8 weeks for Arm A and 12 weeks for Arm B
Title
Proportion of Patients With Renal Insufficiency at Completion of Surgery
Description
Renal insufficiency is defined as CrCl < 60 ml/min.
Time Frame
Assessed at completion of surgery (21-60 days from completion of chemotherapy; chemotherapy was administered for a total of 4 cycles; cycle length is 14 days and 21 days for arms A and B, respectively)

10. Eligibility

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

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
Citations:
PubMed Identifier
31702432
Citation
Margulis V, Puligandla M, Trabulsi EJ, Plimack ER, Kessler ER, Matin SF, Godoy G, Alva A, Hahn NM, Carducci MA, Hoffman-Censits J; Collaborators. Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery in Patients with High Grade Upper Tract Urothelial Carcinoma. J Urol. 2020 Apr;203(4):690-698. doi: 10.1097/JU.0000000000000644. Epub 2019 Nov 8.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs