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.
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.
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)
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There are 116 Locations for this study
Birmingham Alabama, 35233, United States
Aurora Colorado, 80045, United States
Colorado Springs Colorado, 80909, United States
Fort Collins Colorado, 80524, United States
Hartford Connecticut, 06105, United States
Lewes Delaware, 19958, United States
Newark Delaware, 19713, United States
Newark Delaware, 19713, United States
Newark Delaware, 19713, United States
Newark Delaware, 19713, United States
Newark Delaware, 19713, United States
Newark Delaware, 19718, United States
Rehoboth Beach Delaware, 19971, United States
Seaford Delaware, 19973, United States
Wilmington Delaware, 19801, United States
Savannah Georgia, 31405, United States
Savannah Georgia, 31405, United States
Boise Idaho, 83706, United States
Bloomington Illinois, 61701, United States
Bloomington Illinois, 61704, United States
Canton Illinois, 61520, United States
Carbondale Illinois, 62902, United States
Carthage Illinois, 62321, United States
Centralia Illinois, 62801, United States
Danville Illinois, 61832, United States
Decatur Illinois, 62526, United States
Decatur Illinois, 62526, United States
Effingham Illinois, 62401, United States
Effingham Illinois, 62401, United States
Eureka Illinois, 61530, United States
Galesburg Illinois, 61401, United States
Galesburg Illinois, 61401, United States
Kewanee Illinois, 61443, United States
Macomb Illinois, 61455, United States
Mattoon Illinois, 61938, United States
Mount Vernon Illinois, 62864, United States
Ottawa Illinois, 61350, United States
Ottawa Illinois, 61350, United States
Pekin Illinois, 61554, United States
Pekin Illinois, 61554, United States
Peoria Illinois, 61603, United States
Peoria Illinois, 61615, United States
Peoria Illinois, 61615, United States
Peoria Illinois, 61637, United States
Peru Illinois, 61354, United States
Peru Illinois, 61354, United States
Princeton Illinois, 61356, United States
Springfield Illinois, 62702, United States
Springfield Illinois, 62702, United States
Springfield Illinois, 62703, United States
Springfield Illinois, 62781, United States
Swansea Illinois, 62226, United States
Urbana Illinois, 61801, United States
Urbana Illinois, 61801, United States
Michigan City Indiana, 46360, United States
Michigan City Indiana, 46360, United States
Richmond Indiana, 47374, United States
Crestview Hills Kentucky, 41017, United States
New Orleans Louisiana, 70121, United States
Ann Arbor Michigan, 48106, United States
Ann Arbor Michigan, 48109, United States
Dearborn Michigan, 48124, United States
Detroit Michigan, 48236, United States
Flint Michigan, 48502, United States
Flint Michigan, 48503, United States
Jackson Michigan, 49201, United States
Lansing Michigan, 48912, United States
Livonia Michigan, 48154, United States
Pontiac Michigan, 48341, United States
Port Huron Michigan, 48060, United States
Saginaw Michigan, 48601, United States
Warren Michigan, 48093, United States
Bolivar Missouri, 65613, United States
Bonne Terre Missouri, 63628, United States
Branson Missouri, 65616, United States
Cape Girardeau Missouri, 63703, United States
Cape Girardeau Missouri, 63703, United States
Jefferson City Missouri, 65109, United States
Joplin Missouri, 64804, United States
Joplin Missouri, 64804, United States
Rolla Missouri, 65401, United States
Rolla Missouri, 65401, United States
Saint Louis Missouri, 63109, United States
Saint Louis Missouri, 63131, United States
Saint Louis Missouri, 63141, United States
Sainte Genevieve Missouri, 63670, United States
Springfield Missouri, 65804, United States
Springfield Missouri, 65807, United States
Sullivan Missouri, 63080, United States
Sunset Hills Missouri, 63127, United States
Centerville Ohio, 45459, United States
Cincinnati Ohio, 45202, United States
Cincinnati Ohio, 45211, United States
Cincinnati Ohio, 45230, United States
Cincinnati Ohio, 45236, United States
Cincinnati Ohio, 45242, United States
Dayton Ohio, 45406, United States
Dayton Ohio, 45409, United States
Dayton Ohio, 45415, United States
Fairfield Ohio, 45014, United States
Findlay Ohio, 45840, United States
Franklin Ohio, 45005, United States
Greenville Ohio, 45331, United States
Kettering Ohio, 45429, United States
Springfield Ohio, 45504, United States
Springfield Ohio, 45505, United States
Sylvania Ohio, 43560, United States
Troy Ohio, 45373, United States
Oklahoma City Oklahoma, 73104, United States
Tulsa Oklahoma, 74146, United States
Chadds Ford Pennsylvania, 19317, United States
Danville Pennsylvania, 17822, United States
Hazleton Pennsylvania, 18201, United States
Lewisburg Pennsylvania, 17837, United States
Lewistown Pennsylvania, 17044, United States
Philadelphia Pennsylvania, 19103, United States
Philadelphia Pennsylvania, 19107, United States
Pottsville Pennsylvania, 17901, United States
State College Pennsylvania, 16801, United States
Wilkes-Barre Pennsylvania, 18711, United States
Charleston South Carolina, 29425, United States
Franklin Tennessee, 37067, United States
Nashville Tennessee, 37204, United States
Nashville Tennessee, 37232, United States
Dallas Texas, 75390, United States
Burlington Wisconsin, 53105, United States
Grafton Wisconsin, 53024, United States
Marinette Wisconsin, 54143, United States
Menomonee Falls Wisconsin, 53051, United States
Milwaukee Wisconsin, 53209, United States
Oshkosh Wisconsin, 54904, United States
Racine Wisconsin, 53406, United States
Summit Wisconsin, 53066, United States
Waukesha Wisconsin, 53188, United States
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