S1314, Co-expression Extrapolation (COXEN) Program to Predict Chemotherapy Response in Patients With Bladder Cancer

Sponsor

Southwest Oncology Group (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02177695

Collaborator

National Cancer Institute (NCI) (NIH)

237

Enrollment

566

Locations

Arms

Duration (Months)

0.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary focus of this study is to see if looking at tumor biomarkers using a program called coexpression extrapolation or "COXEN" may predict a patient's response to chemotherapy before surgery.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer	Drug: Gemcitabine Drug: Cisplatin Drug: Methotrexate Drug: Vinblastine Drug: Doxorubicin Drug: Filgrastim	Phase 2

Detailed Description

The COXEN program will not select a patient's therapy, but the type of chemotherapy that he/she will receive will be randomly decided. The patient's response to chemotherapy will be used to test the usefulness of the COXEN program, which is the main goal of this trial. Other potential tests to predict a patient's response to chemotherapy will also be evaluated. In this study, the patient may receive the treatment in Arm 1 (gemcitabine and cisplatin) or the treatment in Arm 2 [methotrexate, vinblastine, doxorubicin, cisplatin, and filgrastim (or pegfilgrastim)]. There will be about 230 people taking part in this study (115 in each arm).

Study Design

Study Type:

Interventional

Actual Enrollment :

237 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II Study of Co-Expression Extrapolation (COXEN) With Neoadjuvant Chemotherapy for Localized, Muscle-Invasive Bladder Cancer

Study Start Date :

Jul 1, 2014

Actual Primary Completion Date :

Feb 1, 2020

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine & Cisplatin Gemcitabine, 1000 mg/m2, IV, Days 1&8, q 21 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1, q 21 days x 4 cycles	Drug: Gemcitabine Gemcitabine, 1000 mg/m2, IV (in the vein) on Days 1 and 8 of each 21 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Other Names: Gemzar Drug: Cisplatin Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Other Names: Platinol
Experimental: Dose Dense MVAC Methotrexate, 30 mg/m2, IV, Day 1, q 14 days x 4 cycles Vinblastine, 3 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Doxorubicin, 30 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Filgrastim, 5 mcg/kg, SubQ/IV, Days 3-7, q 14 days x 4 cycles	Drug: Cisplatin Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Other Names: Platinol Drug: Methotrexate Methotrexate, 30 mg/m2, IV (in the vein) on Days 1 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Other Names: Trexall Drug: Vinblastine Vinblastine, 3 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Other Names: Velban Drug: Doxorubicin Doxorubicin, 30 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Other Names: Adriamycin Drug: Filgrastim Filgrastim, 5 mcg/kg, SubQ/IV (in the vein) on Days 3-7 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Other Names: Neupogen

Arm

Intervention/Treatment

Experimental: Gemcitabine & Cisplatin

Gemcitabine, 1000 mg/m2, IV, Days 1&8, q 21 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1, q 21 days x 4 cycles

Drug: Gemcitabine

Gemcitabine, 1000 mg/m2, IV (in the vein) on Days 1 and 8 of each 21 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.

Other Names:

Gemzar

Drug: Cisplatin

Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.

Other Names:

Platinol

Experimental: Dose Dense MVAC

Methotrexate, 30 mg/m2, IV, Day 1, q 14 days x 4 cycles Vinblastine, 3 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Doxorubicin, 30 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Filgrastim, 5 mcg/kg, SubQ/IV, Days 3-7, q 14 days x 4 cycles

Drug: Cisplatin

Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.

Other Names:

Platinol

Drug: Methotrexate

Methotrexate, 30 mg/m2, IV (in the vein) on Days 1 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.

Other Names:

Trexall

Drug: Vinblastine

Vinblastine, 3 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.

Other Names:

Velban

Drug: Doxorubicin

Doxorubicin, 30 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.

Other Names:

Adriamycin

Drug: Filgrastim

Filgrastim, 5 mcg/kg, SubQ/IV (in the vein) on Days 3-7 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.

Other Names:

Neupogen

Outcome Measures

Primary Outcome Measures

Assessment of Whether the Treatment-specific COXEN Score is Prognostic of pT0 Rate [Up to 5 years post registration]
The proportion of participants achieving pT0 in both favorable and unfavorable treatment specific-COXEN score categories. Unit of measure is the number of participants in each category that achieved pT0 _____________________________________________________________________________________________________________________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores This will be done in two ways: By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. . By evaluating the correlation between the GC- and the DDMVAC-COXEN score.
Assessment of Whether the Treatment-specific COXEN Score is Prognostic of ≤ pT1 Rate [up to 5 years post-registration]
The proportion of participants achieving <=pT1 in both favorable and unfavorable treatment specific-COXEN score categories. Unit of measure is the number of participants in each category that achieved <= pT1 ____________________________________________________________________________________________________________________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores This will be done in two ways: By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. . By evaluating the correlation between the GC- and the DDMVAC-COXEN score.
Assessment of COXEN Score as a Predictive Factor Distinguishing Between GC and ddMVAC [up to 5 years post-registration]
To assess in a hypothesis generating fashion, the ability of COXEN to select for an individual chemotherapy regimen (GC vs DDMVAC) P-values are reported as a measure of whether COXEN can select between GC/DDMVAC and to determine the significance of interactions between treatment specific COXEN scores and treatment arms in models predicting either pT0 or <= pT1. Interactions with p-values > 0.05 are interpreted as not significant. ________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores This will be done in two ways: By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. . By evaluating the correlation between the GC- and the DDMVAC-COXEN score.
Correlation Between GC-and ddMVAC-COXEN Score [up to 5 years post-registration]
The Pearson and Spearman correlation coefficients for GC-and ddMVAC-COXEN score were calculated and are reported below. ___________________________________________________________________________________________________________________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores This will be done in two ways: By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. . By evaluating the correlation between the GC- and the DDMVAC-COXEN score.

Secondary Outcome Measures

Predictability of the CO-eXpression ExtrapolatioN (COXEN) Score to Direct Which of the Two Regimens the Patient Should Receive: Gemcitabine+Cisplatin (GC) Versus Dose-dense Methotrexate, Vinblastin, Doxorubicin, and Cisplatin (DDMVAC) [Up to 5 years post registration]
In addition to stratification factors and dichotomous COXEN GEM score, an indicator for treatment arm and the interaction of treatment arm with COXEN GEM score was also included in a logistic regression model. A significant interaction would suggest that the respective COXEN GEM score was able to differentiate whether a patient was more likely to respond to one chemotherapy regimen over another. *note that this is the same objective at Primary Outcome #3 above - this was erroneously listed twice in the protocol.
Overall Survival [Up to 5 years post registration]
Duration from date of randomization to date of death from any cause.
Pathologic T0 Rate Evaluation: Gemcitabine+Cisplatin (GC) Versus Dose-dense Methotrexate, Vinblastin, Doxorubicin, and Cisplatin (DDMVAC) [Up to 5 years post-registration]
Pathologic complete response rate at the time of cystectomy following GC or DDMVAC treatment
Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs [Duration of treatment and follow up until death or 5 years post registration]
Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. Grade 3 is less severe than Grade 5. Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL* (bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden). Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related to AE *ADL- Activities of Daily Living

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically proven bladder cancer (pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma histologies are excluded).
Stage cT2-T4a N0 M0 disease.
Documented muscle invasive disease with at least one of the following: disease measuring at least 10 mm on cross-sectional imaging OR the presence of tumor-associated hydronephrosis.
Staging scans with abdominal/pelvic CT or MRI scan and CT scan or x-ray of the chest within 56 days prior to registration. If alkaline phosphatase is above the treating institution's upper limit of normal (ULN), presence of suspicious bone pain, or if other clinical suspicion, a whole body bone scan is required within 56 days prior to registration.
Performance status = 0 or 1
18 years of age or older
Must have tumor tissue from transurethral resection of the bladder tumor (TURBT) available for submission that is sufficient for COXEN testing and must agree to submission of 20 (10 micron) slides plus 2 (5 micron) slides from the start and end of the 20 slides for a total of 22 unstained slides.
Must agree to collection of tissue (if residual disease is present), urine, and whole blood.
Must agree to participate in the translational medicine studies outlined in the protocol

Exclusion Criteria:

Prior systemic cytotoxic chemotherapy or systemic anthracycline
Peripheral neuropathy >/= Grade 2
Class III/IV heart failure or known left ventricular ejection fraction (LVEF) < 50%
Clinically relevant hearing impairment > Grade 2
Renal function, calculated creatinine clearance < 60 mL/min
Hepatic function, total bilirubin > 1.5 x institutional upper limit of normal (IULN) (or > 2.5 x IULN with Gilbert's disease); AST & ALT > 2 X IULN
Hematologic function, absolute neutrophil count (ANC) < 1,500/mcL, hemoglobin < 9 g/dL, and platelets < 100,000/mcL
Hypersensitivity to cisplatin, gemcitabine, doxorubicin, vinblastine, methotrexate, or filgrastim/pegfilgrastim
Incidence of or uncontrolled medical illness (e.g. active cardiac symptoms, active systemic infection, etc.)
Pregnant or nursing females
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. However, patients with localized prostate cancer who are being followed by an active surveillance program are eligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	Fairbanks Memorial Hospital	Fairbanks	Alaska	United States	99701
3	University of Arizona Cancer Center at Saint Joseph's	Phoenix	Arizona	United States	85004
4	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona	United States	85704
5	University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
6	The University of Arizona Medical Center-University Campus	Tucson	Arizona	United States	85724
7	Yuma Cancer Center	Yuma	Arizona	United States	85364
8	Fowler Family Center for Cancer Care	Jonesboro	Arkansas	United States	72401
9	AIS Cancer Center at San Joaquin Community Hospital	Bakersfield	California	United States	93301
10	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
11	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
12	City of Hope Antelope Valley	Lancaster	California	United States	93534
13	Loma Linda University Medical Center	Loma Linda	California	United States	92354
14	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
15	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
16	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
17	Fremont - Rideout Cancer Center	Marysville	California	United States	95901
18	USC Norris Oncology/Hematology-Newport Beach	Newport Beach	California	United States	92663
19	Stanford Cancer Institute	Palo Alto	California	United States	94304
20	PCR Oncology	Pismo Beach	California	United States	93449
21	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
22	Stanford Cancer Center South Bay	San Jose	California	United States	95124
23	City of Hope South Pasadena	South Pasadena	California	United States	91030
24	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California	United States	96161
25	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado	United States	80012
26	The Medical Center of Aurora	Aurora	Colorado	United States	80012
27	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
28	Boulder Community Hospital	Boulder	Colorado	United States	80301
29	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado	United States	80304
30	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
31	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado	United States	80907
32	Memorial Hospital Central	Colorado Springs	Colorado	United States	80909
33	Denver Health Medical Center	Denver	Colorado	United States	80204
34	National Jewish Health-Main Campus	Denver	Colorado	United States	80206
35	The Women's Imaging Center	Denver	Colorado	United States	80209
36	Porter Adventist Hospital	Denver	Colorado	United States	80210
37	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
38	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
39	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado	United States	80218
40	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
41	Rocky Mountain Cancer Centers-Rose	Denver	Colorado	United States	80220
42	Rose Medical Center	Denver	Colorado	United States	80220
43	Colorado Cancer Research Program NCORP	Denver	Colorado	United States	80222
44	Mercy Medical Center	Durango	Colorado	United States	81301
45	Southwest Oncology PC	Durango	Colorado	United States	81301
46	Comprehensive Cancer Care and Research Institute of Colorado LLC	Englewood	Colorado	United States	80113
47	Swedish Medical Center	Englewood	Colorado	United States	80113
48	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
49	Mountain Blue Cancer Care Center	Golden	Colorado	United States	80401
50	National Jewish Health-Western Hematology Oncology	Golden	Colorado	United States	80401
51	Grand Valley Oncology	Grand Junction	Colorado	United States	81501
52	North Colorado Medical Center	Greeley	Colorado	United States	80631
53	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado	United States	80111
54	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado	United States	80228
55	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
56	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado	United States	80120
57	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
58	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado	United States	80124
59	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
60	Longmont United Hospital	Longmont	Colorado	United States	80501
61	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado	United States	80501
62	McKee Medical Center	Loveland	Colorado	United States	80539
63	Parker Adventist Hospital	Parker	Colorado	United States	80138
64	Rocky Mountain Cancer Centers-Parker	Parker	Colorado	United States	80138
65	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
66	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado	United States	81008
67	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado	United States	80260
68	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
69	Greenwich Hospital	Greenwich	Connecticut	United States	06830
70	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
71	Yale University	New Haven	Connecticut	United States	06520
72	Beebe Medical Center	Lewes	Delaware	United States	19958
73	Christiana Gynecologic Oncology LLC	Newark	Delaware	United States	19713
74	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
75	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
76	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
77	Regional Hematology and Oncology PA	Newark	Delaware	United States	19713
78	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
79	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
80	Nanticoke Memorial Hospital	Seaford	Delaware	United States	19973
81	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
82	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
83	Cleveland Clinic-Weston	Weston	Florida	United States	33331
84	John B Amos Cancer Center	Columbus	Georgia	United States	31904
85	Medical Center of Central Georgia	Macon	Georgia	United States	31201
86	Hawaii Oncology Inc-Pali Momi	'Aiea	Hawaii	United States	96701
87	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
88	The Cancer Center of Hawaii-Leeward	'Ewa Beach	Hawaii	United States	96706
89	Hawaii Cancer Care Inc-POB II	Honolulu	Hawaii	United States	96813
90	Hawaii Oncology Inc-POB I	Honolulu	Hawaii	United States	96813
91	Island Urology	Honolulu	Hawaii	United States	96813
92	Queen's Medical Center	Honolulu	Hawaii	United States	96813
93	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
94	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
95	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii	United States	96817
96	Hawaii Oncology Inc-Kuakini	Honolulu	Hawaii	United States	96817
97	Kuakini Medical Center	Honolulu	Hawaii	United States	96817
98	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii	United States	96817
99	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
100	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
101	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
102	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho	United States	83605
103	Kootenai Medical Center	Coeur d'Alene	Idaho	United States	83814
104	Walter Knox Memorial Hospital	Emmett	Idaho	United States	83617
105	Idaho Urologic Institute-Meridian	Meridian	Idaho	United States	83642
106	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho	United States	83686
107	Kootenai Cancer Center	Post Falls	Idaho	United States	83854
108	Kootenai Cancer Clinic	Sandpoint	Idaho	United States	83864
109	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
110	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
111	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
112	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
113	SIH Cancer Institute	Carterville	Illinois	United States	62918
114	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
115	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
116	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
117	Cancer Care Center of Decatur	Decatur	Illinois	United States	62526
118	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
119	Crossroads Cancer Center	Effingham	Illinois	United States	62401
120	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
121	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
122	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
123	Hines Veterans Administration Hospital	Hines	Illinois	United States	60141
124	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
125	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
126	Loyola University Medical Center	Maywood	Illinois	United States	60153
127	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
128	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois	United States	60451
129	University of Chicago Medicine-Orland Park	Orland Park	Illinois	United States	60462
130	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
131	Radiation Oncology of Northern Illinois	Ottawa	Illinois	United States	61350
132	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
133	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
134	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61603
135	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
136	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois	United States	61615
137	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
138	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
139	Valley Radiation Oncology	Peru	Illinois	United States	61354
140	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
141	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62702
142	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
143	Springfield Clinic	Springfield	Illinois	United States	62702
144	Memorial Medical Center	Springfield	Illinois	United States	62781
145	Cancer Care Specialists of Illinois-Swansea	Swansea	Illinois	United States	62226
146	Memorial and Saint Elizabeth's Health Care Services LLP	Swansea	Illinois	United States	62226
147	Reid Health	Richmond	Indiana	United States	47374
148	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
149	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
150	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
151	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
152	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
153	Newman Regional Health	Emporia	Kansas	United States	66801
154	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
155	Saint Catherine Hospital	Garden City	Kansas	United States	67846
156	Heartland Cancer Center	Great Bend	Kansas	United States	67530
157	Saint Rose Ambulatory and Surgery Center	Great Bend	Kansas	United States	67530
158	Hays Medical Center	Hays	Kansas	United States	67601
159	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
160	University of Kansas Cancer Center-West	Kansas City	Kansas	United States	66112
161	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
162	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
163	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
164	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas	United States	66219
165	Minimally Invasive Surgery Hospital	Lenexa	Kansas	United States	66219
166	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
167	Cancer Center of Kansas-Manhattan	Manhattan	Kansas	United States	66502
168	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
169	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
170	Olathe Medical Center	Olathe	Kansas	United States	66061
171	Menorah Medical Center	Overland Park	Kansas	United States	66209
172	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas	United States	66210
173	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
174	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
175	Via Christi Hospital-Pittsburg	Pittsburg	Kansas	United States	66762
176	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas	United States	66208
177	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
178	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
179	Salina Regional Health Center	Salina	Kansas	United States	67401
180	Saint Francis Hospital and Medical Center - Topeka	Topeka	Kansas	United States	66606
181	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
182	Associates In Womens Health	Wichita	Kansas	United States	67208
183	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
184	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
185	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
186	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
187	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
188	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana	United States	70805
189	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana	United States	70809
190	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
191	Medical Oncology LLC	Baton Rouge	Louisiana	United States	70809
192	Mary Bird Cancer Center/Saint Tammany Parish	Covington	Louisiana	United States	70433
193	North Shore Hematology Oncology Associates Inc	Covington	Louisiana	United States	70433
194	Oncology Center of The South Incorporated	Houma	Louisiana	United States	70360
195	East Jefferson General Hospital	Metairie	Louisiana	United States	70006
196	Maine Center for Cancer Medicine-Scarborough	Scarborough	Maine	United States	04074
197	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
198	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
199	Hickman Cancer Center	Adrian	Michigan	United States	49221
200	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
201	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
202	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
203	IHA Hematology Oncology Consultants-Brighton	Brighton	Michigan	United States	48114
204	Saint Joseph Mercy Brighton	Brighton	Michigan	United States	48114
205	Henry Ford Cancer Institute?Downriver	Brownstown	Michigan	United States	48183
206	IHA Hematology Oncology Consultants-Canton	Canton	Michigan	United States	48188
207	Saint Joseph Mercy Canton Health Center	Canton	Michigan	United States	48188
208	Caro Cancer Center	Caro	Michigan	United States	48723
209	IHA Hematology Oncology Consultants-Chelsea	Chelsea	Michigan	United States	48118
210	Saint Joseph Mercy Chelsea	Chelsea	Michigan	United States	48118
211	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan	United States	48346
212	Newland Medical Associates-Clarkston	Clarkston	Michigan	United States	48346
213	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan	United States	48038
214	Beaumont Hospital-Dearborn	Dearborn	Michigan	United States	48124
215	Henry Ford Medical Center-Fairlane	Dearborn	Michigan	United States	48126
216	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
217	Henry Ford Hospital	Detroit	Michigan	United States	48202
218	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
219	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan	United States	48054
220	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
221	Weisberg Cancer Treatment Center	Farmington Hills	Michigan	United States	48334
222	Botsford General Hospital	Farmington	Michigan	United States	48334
223	Hurley Medical Center	Flint	Michigan	United States	48502
224	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan	United States	48503
225	Genesee Hematology Oncology PC	Flint	Michigan	United States	48503
226	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
227	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
228	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
229	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan	United States	48236
230	Lymphoma Clinic of Michigan	Grosse Pointe Woods	Michigan	United States	48236
231	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan	United States	48236
232	William Beaumont Hospital-Grosse Point	Grosse Pointe	Michigan	United States	48230
233	Allegiance Health	Jackson	Michigan	United States	49201
234	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
235	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
236	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
237	Sparrow Hospital	Lansing	Michigan	United States	48912
238	Hope Cancer Clinic	Livonia	Michigan	United States	48154
239	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
240	Hematology Oncology Associates East PC	Macomb	Michigan	United States	48044
241	Michigan Breast Specialists-Macomb Township	Macomb	Michigan	United States	48044
242	Monroe Cancer Center	Monroe	Michigan	United States	48162
243	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan	United States	48162
244	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
245	Lakeland Community Hospital	Niles	Michigan	United States	49120
246	Henry Ford Medical Center-Columbus	Novi	Michigan	United States	48377
247	21st Century Oncology-Pontiac	Pontiac	Michigan	United States	48341
248	Hope Cancer Center	Pontiac	Michigan	United States	48341
249	Newland Medical Associates-Pontiac	Pontiac	Michigan	United States	48341
250	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
251	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
252	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
253	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan	United States	48309
254	Michigan Cancer Specialists	Roseville	Michigan	United States	48066
255	Oakland Colon and Rectal Association	Royal Oak	Michigan	United States	48067
256	Cancer Care Associates PC	Royal Oak	Michigan	United States	48073
257	Comprehensive Medical Center PLLC	Royal Oak	Michigan	United States	48073
258	Hematology Oncology Consultants PC	Royal Oak	Michigan	United States	48073
259	Oakland Medical Group	Royal Oak	Michigan	United States	48073
260	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
261	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
262	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan	United States	48604
263	Lakeland Hospital	Saint Joseph	Michigan	United States	49085
264	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
265	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan	United States	48312
266	Premier Hematology Oncology Care	Sterling Heights	Michigan	United States	48312
267	Mitchell Folbe MD PC	Sterling Heights	Michigan	United States	48314
268	Munson Medical Center	Traverse City	Michigan	United States	49684
269	Michigan Institute of Urology-Town Center	Troy	Michigan	United States	48084
270	Claudia BR Herke MD PC	Troy	Michigan	United States	48085
271	Hematology Oncology Consultants PC-Troy	Troy	Michigan	United States	48098
272	William Beaumont Hospital - Troy	Troy	Michigan	United States	48098
273	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan	United States	48093
274	Macomb Hematology Oncology PC	Warren	Michigan	United States	48093
275	Michigan Breast Specialists-Warren	Warren	Michigan	United States	48093
276	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
277	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan	United States	48322
278	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan	United States	48661
279	Metro Health Hospital	Wyoming	Michigan	United States	49519
280	Huron Gastroenterology PC	Ypsilanti	Michigan	United States	48106
281	IHA Hematology Oncology Consultants-Ann Arbor	Ypsilanti	Michigan	United States	48197
282	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota	United States	56401
283	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
284	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
285	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
286	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota	United States	56537
287	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
288	Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
289	Central Care Cancer Center-Carrie J Babb Cancer Center	Bolivar	Missouri	United States	65613
290	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri	United States	63628
291	CoxHealth Cancer Center	Branson	Missouri	United States	65616
292	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
293	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
294	Barnes-Jewish West County Hospital	Creve Coeur	Missouri	United States	63141
295	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
296	Capital Region Medical Center-Goldschmidt Cancer Center	Jefferson City	Missouri	United States	65109
297	Freeman Health System	Joplin	Missouri	United States	64804
298	Mercy Hospital-Joplin	Joplin	Missouri	United States	64804
299	Truman Medical Center	Kansas City	Missouri	United States	64108
300	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
301	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
302	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri	United States	64128
303	The University of Kansas Cancer Center-South	Kansas City	Missouri	United States	64131
304	Research Medical Center	Kansas City	Missouri	United States	64132
305	The University of Kansas Cancer Center-North	Kansas City	Missouri	United States	64154
306	The University of Kansas Cancer Center-Lee's Summit	Lee's Summit	Missouri	United States	64064
307	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
308	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
309	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
310	Saint John's Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
311	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
312	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
313	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
314	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
315	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
316	Siteman Cancer Center - Saint Peters	Saint Peters	Missouri	United States	63376
317	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri	United States	63670
318	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
319	CoxHealth South Hospital	Springfield	Missouri	United States	65807
320	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
321	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
322	Community Hospital of Anaconda	Anaconda	Montana	United States	59711
323	Billings Clinic Cancer Center	Billings	Montana	United States	59101
324	Saint Vincent Healthcare	Billings	Montana	United States	59101
325	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
326	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
327	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
328	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
329	Great Falls Clinic	Great Falls	Montana	United States	59405
330	Saint Peter's Community Hospital	Helena	Montana	United States	59601
331	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
332	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
333	Community Medical Hospital	Missoula	Montana	United States	59804
334	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
335	Carson Tahoe Regional Medical Center	Carson City	Nevada	United States	89703
336	Cancer and Blood Specialists-Henderson	Henderson	Nevada	United States	89052
337	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada	United States	89052
338	Las Vegas Cancer Center-Henderson	Henderson	Nevada	United States	89052
339	21st Century Oncology - Henderson	Henderson	Nevada	United States	89074
340	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada	United States	89074
341	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
342	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada	United States	89106
343	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
344	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada	United States	89106
345	21st Century Oncology	Las Vegas	Nevada	United States	89109
346	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada	United States	89109
347	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada	United States	89113
348	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada	United States	89119
349	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada	United States	89121
350	Ann M Wierman MD LTD	Las Vegas	Nevada	United States	89128
351	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada	United States	89128
352	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada	United States	89128
353	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada	United States	89128
354	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada	United States	89144
355	Summerlin Hospital Medical Center	Las Vegas	Nevada	United States	89144
356	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada	United States	89148-2405
357	21st Century Oncology - Fort Apache	Las Vegas	Nevada	United States	89148
358	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89148
359	Nevada Cancer Specialists-Fort Apache	Las Vegas	Nevada	United States	89148
360	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada	United States	89149
361	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada	United States	89169
362	University Cancer Center	Las Vegas	Nevada	United States	89169
363	21st Century Oncology - Vegas Tenaya	Las Vegas	Nevada	United States	89182
364	Renown Regional Medical Center	Reno	Nevada	United States	89502
365	Saint Mary's Regional Medical Center	Reno	Nevada	United States	89503
366	Inspira Medical Center Vineland	Vineland	New Jersey	United States	08360
367	Inspira Medical Center Woodbury	Woodbury	New Jersey	United States	08096
368	Montefiore Medical Center-Einstein Campus	Bronx	New York	United States	10461
369	Montefiore Medical Center-Weiler Hospital	Bronx	New York	United States	10461
370	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467-2490
371	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
372	Glens Falls Hospital	Glens Falls	New York	United States	12801
373	Weill Medical College of Cornell University	New York	New York	United States	10065
374	University of Rochester	Rochester	New York	United States	14642
375	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
376	Asheville Hematology-Oncology Associates	Asheville	North Carolina	United States	28803
377	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
378	Sampson Radiation Oncology	Clinton	North Carolina	United States	28328
379	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina	United States	28328
380	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina	United States	27534
381	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
382	Wayne Radiation Oncology	Goldsboro	North Carolina	United States	27534
383	Park Ridge Hospital Breast Health Center	Hendersonville	North Carolina	United States	28792
384	Onslow Memorial Hospital	Jacksonville	North Carolina	United States	28546
385	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina	United States	28546
386	Kinston Medical Specialists PA	Kinston	North Carolina	United States	28501
387	Southeastern Medical Oncology Center-Wilson	Wilson	North Carolina	United States	27893
388	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
389	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota	United States	58103
390	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio	United States	45459
391	Miami Valley Hospital South	Centerville	Ohio	United States	45459
392	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio	United States	45236
393	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
394	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
395	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
396	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
397	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
398	Miami Valley Hospital	Dayton	Ohio	United States	45409
399	Dayton Physicians LLC-Samaritan North	Dayton	Ohio	United States	45415
400	Samaritan North Health Center	Dayton	Ohio	United States	45415
401	Armes Family Cancer Center	Findlay	Ohio	United States	45840
402	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
403	Orion Cancer Care	Findlay	Ohio	United States	45840
404	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
405	Dayton Physicians LLC-Atrium	Franklin	Ohio	United States	45005
406	Dayton Physicians LLC-Wayne	Greenville	Ohio	United States	45331
407	Wayne Hospital	Greenville	Ohio	United States	45331
408	Cleveland Clinic Cancer Center Independence	Independence	Ohio	United States	44131
409	Greater Dayton Cancer Center	Kettering	Ohio	United States	45409
410	First Dayton Cancer Care	Kettering	Ohio	United States	45420
411	Kettering Medical Center	Kettering	Ohio	United States	45429
412	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio	United States	44906
413	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
414	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
415	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
416	Dayton Physicians LLC-Signal Point	Middletown	Ohio	United States	45042
417	Saint Charles Hospital	Oregon	Ohio	United States	43616
418	Mercy Health Perrysburg Cancer Center	Perrysburg	Ohio	United States	43551
419	North Coast Cancer Care	Sandusky	Ohio	United States	44870
420	Dayton Physicians LLC-Wilson	Sidney	Ohio	United States	45365
421	Springfield Regional Cancer Center	Springfield	Ohio	United States	45504
422	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
423	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio	United States	44136
424	Flower Hospital	Sylvania	Ohio	United States	43560
425	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
426	University of Toledo	Toledo	Ohio	United States	43614
427	Mercy Saint Anne Hospital	Toledo	Ohio	United States	43623
428	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
429	Dayton Physicians LLC-Upper Valley	Troy	Ohio	United States	45373
430	Upper Valley Medical Center	Troy	Ohio	United States	45373
431	South Pointe Hospital	Warrensville Heights	Ohio	United States	44122
432	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio	United States	44691
433	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
434	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
435	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon	United States	97814
436	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon	United States	97914
437	Oregon Health and Science University	Portland	Oregon	United States	97239
438	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
439	UPMC-Heritage Valley Health System Beaver	Beaver	Pennsylvania	United States	15009
440	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
441	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania	United States	19317
442	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
443	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania	United States	15601
444	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
445	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania	United States	15901
446	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania	United States	17837
447	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
448	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania	United States	15132
449	UPMC-Coraopolis/Heritage Valley Radiation Oncology	Moon	Pennsylvania	United States	15108
450	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
451	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
452	UPMC-Presbyterian Hospital	Pittsburgh	Pennsylvania	United States	15213
453	UPMC-Saint Margaret	Pittsburgh	Pennsylvania	United States	15215
454	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
455	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania	United States	15232
456	UPMC Jefferson Regional Radiation Oncology	Pittsburgh	Pennsylvania	United States	15236
457	UPMC-Passavant Hospital	Pittsburgh	Pennsylvania	United States	15237
458	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania	United States	15243
459	Geisinger Medical Oncology-Pottsville	Pottsville	Pennsylvania	United States	17901
460	Community Medical Center	Scranton	Pennsylvania	United States	18510
461	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania	United States	17870
462	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania	United States	16346
463	Geisinger Medical Group	State College	Pennsylvania	United States	16801
464	UPMC Uniontown Hospital Radiation Oncology	Uniontown	Pennsylvania	United States	15401
465	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania	United States	15301
466	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
467	Medical University of South Carolina	Charleston	South Carolina	United States	29425
468	Greenville Health System Cancer Institute-Easley	Easley	South Carolina	United States	29640
469	Saint Francis Hospital	Greenville	South Carolina	United States	29601
470	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina	United States	29605
471	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina	United States	29605
472	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina	United States	29605
473	Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
474	Saint Francis Cancer Center	Greenville	South Carolina	United States	29607
475	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina	United States	29615
476	Greenville Health System Cancer Institute-Greer	Greer	South Carolina	United States	29650
477	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina	United States	29672
478	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina	United States	29307
479	Wellmont Bristol Regional Medical Center	Bristol	Tennessee	United States	37620
480	Vanderbilt-Ingram Cancer Center Cool Springs	Franklin	Tennessee	United States	37067
481	Wellmont Medical Associates Oncology and Hematology-Johnson City	Johnson City	Tennessee	United States	37604
482	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
483	Wellmont Medical Associates Oncology and Hematology-Kingsport	Kingsport	Tennessee	United States	37660
484	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee	United States	37204
485	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
486	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
487	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
488	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas	United States	76104
489	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
490	Ben Taub General Hospital	Houston	Texas	United States	77030
491	M D Anderson Cancer Center	Houston	Texas	United States	77030
492	Cancer Therapy and Research Center at The UT Health Science Center at San Antonio	San Antonio	Texas	United States	78229
493	University Hospital	San Antonio	Texas	United States	78229
494	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
495	Farmington Health Center	Farmington	Utah	United States	84025
496	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
497	South Jordan Health Center	South Jordan	Utah	United States	84009
498	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
499	University of Vermont Medical Center	Burlington	Vermont	United States	05401
500	University of Vermont College of Medicine	Burlington	Vermont	United States	05405
501	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
502	Southwest VA Regional Cancer Center	Norton	Virginia	United States	24273
503	MultiCare Auburn Medical Center	Auburn	Washington	United States	98001
504	Virginia Mason Bainbridge Island Medical Center	Bainbridge Island	Washington	United States	98110
505	Overlake Hospital Medical Center	Bellevue	Washington	United States	98004
506	Virginia Mason Federal Way Medical Center	Federal Way	Washington	United States	98002
507	Tacoma/Valley Radiation Oncology Centers-Gig Harbor	Gig Harbor	Washington	United States	98332
508	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington	United States	98335
509	Northwest Cancer Clinic	Kennewick	Washington	United States	99336
510	Virginia Mason Lynnwood Medical Center	Lynnwood	Washington	United States	98036
511	Jefferson Healthcare	Port Townsend	Washington	United States	98368
512	Peninsula Cancer Center	Poulsbo	Washington	United States	98370
513	MultiCare Good Samaritan Hospital	Puyallup	Washington	United States	98372
514	Tacoma/Valley Radiation Oncology Centers-Puyallup	Puyallup	Washington	United States	98372
515	Virginia Mason Medical Center	Seattle	Washington	United States	98101
516	Tacoma/Valley Radiation Oncology Centers-Jackson Hall	Tacoma	Washington	United States	97405
517	MultiCare Tacoma General Hospital	Tacoma	Washington	United States	98405
518	Northwest NCI Community Oncology Research Program	Tacoma	Washington	United States	98405
519	Tacoma/Valley Radiation Oncology Centers-Saint Joe's	Tacoma	Washington	United States	98405
520	West Virginia University Charleston	Charleston	West Virginia	United States	25304
521	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
522	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
523	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
524	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin	United States	54937
525	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
526	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
527	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
528	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
529	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
530	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
531	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
532	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
533	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
534	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
535	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin	United States	54143
536	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
537	Vince Lombardi Cancer Clinic-Marinette	Marinette	Wisconsin	United States	54143
538	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
539	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin	United States	53209
540	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
541	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
542	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
543	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
544	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
545	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
546	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
547	Lakeview Medical Center-Marshfield Clinic	Rice Lake	Wisconsin	United States	54868
548	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin	United States	54868
549	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
550	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
551	Marshfield Clinic Cancer Care at Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
552	Marshfield Clinic Stevens Point Center	Stevens Point	Wisconsin	United States	54482
553	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235-1495
554	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
555	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
556	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
557	Aurora Cancer Care-Waukesha	Waukesha	Wisconsin	United States	53188
558	Marshfield Clinic-Wausau Center	Wausau	Wisconsin	United States	54401
559	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
560	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227
561	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
562	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
563	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming	United States	82001
564	Big Horn Basin Cancer Center	Cody	Wyoming	United States	82414
565	Billings Clinic-Cody	Cody	Wyoming	United States	82414
566	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

Southwest Oncology Group
National Cancer Institute (NCI)

Investigators

Study Chair: Thomas W. Flaig, M.D., University of Colorado, Denver

Study Documents (Full-Text)

Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Jul 15, 2019

More Information

Publications

None provided.

Responsible Party:

Southwest Oncology Group

ClinicalTrials.gov Identifier:

NCT02177695

Other Study ID Numbers:

S1314
S1314
NCI-2014-00850
U10CA180888

First Posted:

Jun 30, 2014

Last Update Posted:

Jan 3, 2022

Last Verified:

Dec 1, 2021

Keywords provided by Southwest Oncology Group

Bladder Cancer

Neoadjuvant Chemotherapy

Coexpression Extrapolation

COXEN

S1314

SWOG

Additional relevant MeSH terms:

Urinary Bladder Neoplasms

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	237 participants were enrolled, but 10 were ineligible due to missing tissue, inadequate disease assessment and inadequate kidney function.

Arm/Group Title	Gemcitabine & Cisplatin	Dose Dense MVAC
Arm/Group Description	Gemcitabine, 1000 mg/m2, IV, Days 1&8, q 21 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1, q 21 days x 4 cycles Gemcitabine: Gemcitabine, 1000 mg/m2, IV (in the vein) on Days 1 and 8 of each 21 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.	Methotrexate, 30 mg/m2, IV, Day 1, q 14 days x 4 cycles Vinblastine, 3 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Doxorubicin, 30 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Filgrastim, 5 mcg/kg, SubQ/IV, Days 3-7, q 14 days x 4 cycles Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Methotrexate: Methotrexate, 30 mg/m2, IV (in the vein) on Days 1 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Vinblastine: Vinblastine, 3 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Doxorubicin: Doxorubicin, 30 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Filgrastim: Filgrastim, 5 mcg/kg, SubQ/IV (in the vein) on Days 3-7 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.
Period Title: ITT Analysis
STARTED	120	117
COMPLETED	115	112
NOT COMPLETED	5	5
Period Title: ITT Analysis
STARTED	115	112
Participants Excluded From Primary COXEN Analysis	33	27
COMPLETED	82	85
NOT COMPLETED	33	27

Baseline Characteristics

Arm/Group Title	Gemcitabine & Cisplatin	Dose Dense MVAC	Total
Arm/Group Description	Gemcitabine, 1000 mg/m2, IV, Days 1&8, q 21 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1, q 21 days x 4 cycles Gemcitabine: Gemcitabine, 1000 mg/m2, IV (in the vein) on Days 1 and 8 of each 21 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.	Methotrexate, 30 mg/m2, IV, Day 1, q 14 days x 4 cycles Vinblastine, 3 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Doxorubicin, 30 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Filgrastim, 5 mcg/kg, SubQ/IV, Days 3-7, q 14 days x 4 cycles Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Methotrexate: Methotrexate, 30 mg/m2, IV (in the vein) on Days 1 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Vinblastine: Vinblastine, 3 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Doxorubicin: Doxorubicin, 30 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Filgrastim: Filgrastim, 5 mcg/kg, SubQ/IV (in the vein) on Days 3-7 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.	Total of all reporting groups
Overall Participants	115	112	227
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64.9	64.8	64.8
Sex: Female, Male (Count of Participants)
Female	23 20%	13 11.6%	36 15.9%
Male	92 80%	99 88.4%	191 84.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 6.1%	5 4.5%	12 5.3%
Not Hispanic or Latino	104 90.4%	105 93.8%	209 92.1%
Unknown or Not Reported	4 3.5%	2 1.8%	6 2.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.9%	1 0.4%
Asian	4 3.5%	1 0.9%	5 2.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 6.1%	1 0.9%	8 3.5%
White	94 81.7%	107 95.5%	201 88.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	10 8.7%	2 1.8%	12 5.3%
Clinical stage (Count of Participants)
T2	102 88.7%	98 87.5%	200 88.1%
T3 or T4a	13 11.3%	14 12.5%	27 11.9%
Zubrod performance status (Count of Participants)
0	88 76.5%	86 76.8%	174 76.7%
1	27 23.5%	26 23.2%	53 23.3%
GC-COXEN score (Count of Participants)
Favorable	18 15.7%	25 22.3%	43 18.9%
Not favorable	64 55.7%	60 53.6%	124 54.6%
ddMVAC-COXEN score (Count of Participants)
Favorable	23 20%	30 26.8%	53 23.3%
Not Favorable	59 51.3%	55 49.1%	114 50.2%

Outcome Measures

1. Primary Outcome

Title	Assessment of Whether the Treatment-specific COXEN Score is Prognostic of pT0 Rate
Description	The proportion of participants achieving pT0 in both favorable and unfavorable treatment specific-COXEN score categories. Unit of measure is the number of participants in each category that achieved pT0 _____________________________________________________________________________________________________________________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores This will be done in two ways: By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. . By evaluating the correlation between the GC- and the DDMVAC-COXEN score.
Time Frame	Up to 5 years post registration

Outcome Measure Data

Analysis Population Description
Eligible participants that were evaluable for COXEN analysis

Arm/Group Title	Gemcitabine & Cisplatin	Dose Dense MVAC
Arm/Group Description	Gemcitabine, 1000 mg/m2, IV, Days 1&8, q 21 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1, q 21 days x 4 cycles Gemcitabine: Gemcitabine, 1000 mg/m2, IV (in the vein) on Days 1 and 8 of each 21 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.	Methotrexate, 30 mg/m2, IV, Day 1, q 14 days x 4 cycles Vinblastine, 3 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Doxorubicin, 30 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Filgrastim, 5 mcg/kg, SubQ/IV, Days 3-7, q 14 days x 4 cycles Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Methotrexate: Methotrexate, 30 mg/m2, IV (in the vein) on Days 1 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Vinblastine: Vinblastine, 3 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Doxorubicin: Doxorubicin, 30 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Filgrastim: Filgrastim, 5 mcg/kg, SubQ/IV (in the vein) on Days 3-7 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.
Measure Participants	82	85
Favorable treatment-COXEN score	8 7%	10 8.9%
Unfavorable treatment-COXEN score	20 17.4%	17 15.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gemcitabine & Cisplatin
	Comments	To determine the relationship of GC COXEN scores to pT0, GC COXEN score (dichotomous, favorable vs. unfavorable) was tested in a logistic regression model predicting the outcome of pT0 within the GC treatment group.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.63
	Confidence Interval	(2-Sided) 95% 0.82 to 8.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dose Dense MVAC
	Comments	To determine the relationship of ddMVAC COXEN scores to pT0, ddMVAC COXEN score (dichotomous, favorable vs. unfavorable) was tested in a logistic regression model predicting the outcome of pT0 within the ddMVAC treatment group.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.82
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95% 0.42 to 2.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Assessment of Whether the Treatment-specific COXEN Score is Prognostic of ≤ pT1 Rate
Description	The proportion of participants achieving <=pT1 in both favorable and unfavorable treatment specific-COXEN score categories. Unit of measure is the number of participants in each category that achieved <= pT1 ____________________________________________________________________________________________________________________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores This will be done in two ways: By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. . By evaluating the correlation between the GC- and the DDMVAC-COXEN score.
Time Frame	up to 5 years post-registration

Outcome Measure Data

Analysis Population Description
Eligible participants that were evaluable for COXEN analysis

Arm/Group Title	Gemcitabine & Cisplatin	Dose Dense MVAC
Arm/Group Description	Gemcitabine, 1000 mg/m2, IV, Days 1&8, q 21 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1, q 21 days x 4 cycles Gemcitabine: Gemcitabine, 1000 mg/m2, IV (in the vein) on Days 1 and 8 of each 21 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.	Methotrexate, 30 mg/m2, IV, Day 1, q 14 days x 4 cycles Vinblastine, 3 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Doxorubicin, 30 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Filgrastim, 5 mcg/kg, SubQ/IV, Days 3-7, q 14 days x 4 cycles Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Methotrexate: Methotrexate, 30 mg/m2, IV (in the vein) on Days 1 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Vinblastine: Vinblastine, 3 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Doxorubicin: Doxorubicin, 30 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Filgrastim: Filgrastim, 5 mcg/kg, SubQ/IV (in the vein) on Days 3-7 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.
Measure Participants	82	85
Favorable treatment-COXEN score	10 8.7%	16 14.3%
Unfavorable treatment-COXEN score	30 26.1%	31 27.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gemcitabine & Cisplatin
	Comments	To determine the relationship of GC COXEN scores to <= pT1, GC COXEN score (dichotomous, favorable vs. unfavorable) was tested in a logistic regression model predicting the outcome of pT1 or better within the GC treatment group.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.33
	Confidence Interval	(2-Sided) 95% 1.11 to 4.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dose Dense MVAC
	Comments	To determine the relationship of ddMVAC COXEN scores to <=pT1, ddMVAC COXEN score (dichotomous, favorable vs. unfavorable) was tested in a logistic regression model predicting the outcome of pT1 or better within the ddMVAC treatment group.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95% 0.46 to 1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Assessment of COXEN Score as a Predictive Factor Distinguishing Between GC and ddMVAC
Description	To assess in a hypothesis generating fashion, the ability of COXEN to select for an individual chemotherapy regimen (GC vs DDMVAC) P-values are reported as a measure of whether COXEN can select between GC/DDMVAC and to determine the significance of interactions between treatment specific COXEN scores and treatment arms in models predicting either pT0 or <= pT1. Interactions with p-values > 0.05 are interpreted as not significant. ________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores This will be done in two ways: By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. . By evaluating the correlation between the GC- and the DDMVAC-COXEN score.
Time Frame	up to 5 years post-registration

Outcome Measure Data

Analysis Population Description
Eligible participants that were evaluable for COXEN analysis. Participants in this arm were pooled to test the ability of the COXEN algorithm to distinguish between GC and ddMVAC treatment, with the assumption that there is no interaction between the COXEN score and treatment arm.

Arm/Group Title	All Participants
Arm/Group Description	Eligible participants that were evaluable for COXEN analysis
Measure Participants	167
P-value of interaction term (GCscore*treatment arm) in model predicting pT0	0.88
P-value of interaction term (GCscore*treatment arm) in logistic regression model predicting <=pT1	0.43
P-value of interaction term (MVACscore*treatment arm) in logistic regression model predicting pT0	0.66
P-value of interaction term (MVACscore*treatment arm) in logistic regression model predicting <=pT1	0.85

4. Primary Outcome

Title	Correlation Between GC-and ddMVAC-COXEN Score
Description	The Pearson and Spearman correlation coefficients for GC-and ddMVAC-COXEN score were calculated and are reported below. ___________________________________________________________________________________________________________________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores This will be done in two ways: By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. . By evaluating the correlation between the GC- and the DDMVAC-COXEN score.
Time Frame	up to 5 years post-registration

Outcome Measure Data

Analysis Population Description
Eligible participants that were evaluable for COXEN analysis. Participants in this arm were pooled to test the ability of the COXEN algorithm to distinguish between GC and ddMVAC treatment, with the assumption that there is no interaction between the COXEN score and treatment arm.

Arm/Group Title	All Participants
Arm/Group Description	Eligible participants that were evaluable for COXEN analysis
Measure Participants	167
Pearson correlation coefficient	0.385
Spearman correlation coefficient	0.386

5. Secondary Outcome

Title	Predictability of the CO-eXpression ExtrapolatioN (COXEN) Score to Direct Which of the Two Regimens the Patient Should Receive: Gemcitabine+Cisplatin (GC) Versus Dose-dense Methotrexate, Vinblastin, Doxorubicin, and Cisplatin (DDMVAC)
Description	In addition to stratification factors and dichotomous COXEN GEM score, an indicator for treatment arm and the interaction of treatment arm with COXEN GEM score was also included in a logistic regression model. A significant interaction would suggest that the respective COXEN GEM score was able to differentiate whether a patient was more likely to respond to one chemotherapy regimen over another. *note that this is the same objective at Primary Outcome #3 above - this was erroneously listed twice in the protocol.
Time Frame	Up to 5 years post registration

Outcome Measure Data

Analysis Population Description
Eligible participants that were evaluable for COXEN analysis. Participants in this arm were pooled to test the ability of the COXEN algorithm to distinguish between GC and ddMVAC treatment, with the assumption that there is no interaction between the COXEN score and treatment arm.

Arm/Group Title	All Participants
Arm/Group Description	Eligible participants that were evaluable for COXEN analysis
Measure Participants	167
Pvalue of interaction term (GCscore*treatment arm) in model predicting pT0	0.88
Pvalue of interaction term (GCscore*treatment arm) in model predicting <=pT1	0.43
Pvalue of interaction term (MVACscore*treatment arm) in model predicting pT0	0.66
Pvalue of interaction term (MVACscore*treatment arm) in model predicting <=pT1	0.85

6. Secondary Outcome

Title	Overall Survival
Description	Duration from date of randomization to date of death from any cause.
Time Frame	Up to 5 years post registration

Outcome Measure Data

Analysis Population Description
[Not Specified]

Arm/Group Title
Arm/Group Description

7. Secondary Outcome

Title	Pathologic T0 Rate Evaluation: Gemcitabine+Cisplatin (GC) Versus Dose-dense Methotrexate, Vinblastin, Doxorubicin, and Cisplatin (DDMVAC)
Description	Pathologic complete response rate at the time of cystectomy following GC or DDMVAC treatment
Time Frame	Up to 5 years post-registration

Outcome Measure Data

Analysis Population Description
eligible participants

Arm/Group Title	Gemcitabine & Cisplatin	Dose Dense MVAC
Arm/Group Description	Gemcitabine, 1000 mg/m2, IV, Days 1&8, q 21 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1, q 21 days x 4 cycles Gemcitabine: Gemcitabine, 1000 mg/m2, IV (in the vein) on Days 1 and 8 of each 21 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.	Methotrexate, 30 mg/m2, IV, Day 1, q 14 days x 4 cycles Vinblastine, 3 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Doxorubicin, 30 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Filgrastim, 5 mcg/kg, SubQ/IV, Days 3-7, q 14 days x 4 cycles Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Methotrexate: Methotrexate, 30 mg/m2, IV (in the vein) on Days 1 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Vinblastine: Vinblastine, 3 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Doxorubicin: Doxorubicin, 30 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Filgrastim: Filgrastim, 5 mcg/kg, SubQ/IV (in the vein) on Days 3-7 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.
Measure Participants	115	112
Number [percentage of participants]	28 24.3%	30 26.8%

8. Secondary Outcome

Title	Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Description	Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. Grade 3 is less severe than Grade 5. Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL* (bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden). Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related to AE *ADL- Activities of Daily Living
Time Frame	Duration of treatment and follow up until death or 5 years post registration

Outcome Measure Data

Analysis Population Description
Participants who received at least one dose of protocol treatment, submitted toxicity data and were included in the ITT analysis.

Arm/Group Title	Gemcitabine and Cisplatin	Dose Dense MVAC
Arm/Group Description	Gemcitabine, 1000 mg/m2, IV, Days 1 and 8, q 21 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1, q 21 days x 4 cycles Gemcitabine: Gemcitabine, 1000 mg/m2, IV (in the vein) on Days 1 and 8 of each 21 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.	Methotrexate, 30 mg/m2, IV, Day 1, q 14 days x 4 cycles Vinblastine, 3 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Doxorubicin, 30 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Filgrastim, 5 mcg/kg, SubQ/IV, Days 3-7, q 14 days x 4 cycles Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Methotrexate: Methotrexate, 30 mg/m2, IV (in the vein) on Days 1 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Vinblastine: Vinblastine, 3 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Doxorubicin: Doxorubicin, 30 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Filgrastim: Filgrastim, 5 mcg/kg, SubQ/IV (in the vein) on Days 3-7 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.
Measure Participants	115	112
Acute kidney injury	0 0%	1 0.9%
Alanine aminotransferase increased	1 0.9%	0 0%
Anemia	10 8.7%	9 8%
Bronchial infection	0 0%	1 0.9%
Cardiac arrest	0 0%	1 0.9%
Cardiac disorders - Other, specify	1 0.9%	0 0%
Chronic kidney disease	2 1.7%	1 0.9%
Creatinine increased	0 0%	5 4.5%
Dehydration	0 0%	2 1.8%
Diarrhea	0 0%	2 1.8%
Dizziness	1 0.9%	0 0%
Dyspnea	1 0.9%	0 0%
Enterocolitis infectious	0 0%	1 0.9%
Erectile dysfunction	1 0.9%	0 0%
Esophagitis	0 0%	1 0.9%
Fall	0 0%	1 0.9%
Fatigue	3 2.6%	5 4.5%
Febrile neutropenia	2 1.7%	2 1.8%
Headache	0 0%	1 0.9%
Heart failure	0 0%	1 0.9%
Hematuria	0 0%	1 0.9%
Hyperglycemia	3 2.6%	2 1.8%
Hyperkalemia	2 1.7%	0 0%
Hypertension	1 0.9%	3 2.7%
Hypocalcemia	0 0%	1 0.9%
Hypokalemia	0 0%	3 2.7%
Hypomagnesemia	0 0%	2 1.8%
Hyponatremia	5 4.3%	2 1.8%
Hypophosphatemia	1 0.9%	0 0%
Infections and infestations - Other, specify	0 0%	3 2.7%
Insomnia	0 0%	1 0.9%
Investigations - Other, specify	0 0%	1 0.9%
Kidney infection	1 0.9%	0 0%
Lung infection	0 0%	1 0.9%
Lymphocyte count decreased	2 1.7%	3 2.7%
Mucositis oral	0 0%	5 4.5%
Nausea	1 0.9%	3 2.7%
Neutrophil count decreased	20 17.4%	10 8.9%
Phlebitis infective	1 0.9%	0 0%
Platelet count decreased	11 9.6%	5 4.5%
Proteinuria	1 0.9%	0 0%
Renal and urinary disorders - Other, specify	1 0.9%	0 0%
Sepsis	0 0%	1 0.9%
Syncope	1 0.9%	1 0.9%
Thromboembolic event	4 3.5%	1 0.9%
Tinnitus	1 0.9%	0 0%
Upper gastrointestinal hemorrhage	0 0%	1 0.9%
Urinary tract infection	4 3.5%	3 2.7%
Urinary tract obstruction	1 0.9%	1 0.9%
Vestibular disorder	0 0%	1 0.9%
Vomiting	0 0%	3 2.7%
White blood cell decreased	5 4.3%	6 5.4%

Adverse Events

	Gemcitabine and Cisplatin		Dose Dense MVAC
Time Frame	Duration of treatment and follow up until death or 5 years post registration
Adverse Event Reporting Description	Participants who received protocol treatment and are included in the ITT analysis

Arm/Group Title	Gemcitabine and Cisplatin		Dose Dense MVAC
Arm/Group Description	Gemcitabine, 1000 mg/m2, IV, Days 1 and 8, q 21 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1, q 21 days x 4 cycles Gemcitabine: Gemcitabine, 1000 mg/m2, IV (in the vein) on Days 1 and 8 of each 21 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.		Methotrexate, 30 mg/m2, IV, Day 1, q 14 days x 4 cycles Vinblastine, 3 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Doxorubicin, 30 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Filgrastim, 5 mcg/kg, SubQ/IV, Days 3-7, q 14 days x 4 cycles Cisplatin: Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle). Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Methotrexate: Methotrexate, 30 mg/m2, IV (in the vein) on Days 1 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Vinblastine: Vinblastine, 3 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Doxorubicin: Doxorubicin, 30 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops. Filgrastim: Filgrastim, 5 mcg/kg, SubQ/IV (in the vein) on Days 3-7 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/115 (24.3%)		25/112 (22.3%)
Serious Adverse Events
	Gemcitabine and Cisplatin		Dose Dense MVAC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/115 (0.9%)		4/112 (3.6%)
Blood and lymphatic system disorders
Febrile neutropenia	0/115 (0%)		1/112 (0.9%)
Cardiac disorders
Cardiac arrest	1/115 (0.9%)		1/112 (0.9%)
Gastrointestinal disorders
Upper gastrointestinal hemorrhage	0/115 (0%)		1/112 (0.9%)
General disorders
Sudden death NOS	0/115 (0%)		1/112 (0.9%)
Infections and infestations
Infections and infestations-Other	0/115 (0%)		2/112 (1.8%)
Sepsis	0/115 (0%)		1/112 (0.9%)
Other (Not Including Serious) Adverse Events
	Gemcitabine and Cisplatin		Dose Dense MVAC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	112/115 (97.4%)		108/112 (96.4%)
Blood and lymphatic system disorders
Anemia	83/115 (72.2%)		69/112 (61.6%)
Blood and lymphatic system disorders - Other	2/115 (1.7%)		1/112 (0.9%)
Febrile neutropenia	2/115 (1.7%)		1/112 (0.9%)
Leukocytosis	0/115 (0%)		1/112 (0.9%)
Cardiac disorders
Atrial flutter	0/115 (0%)		1/112 (0.9%)
Cardiac disorders-Other	1/115 (0.9%)		2/112 (1.8%)
Chest pain - cardiac	1/115 (0.9%)		1/112 (0.9%)
Heart failure	0/115 (0%)		1/112 (0.9%)
Mitral valve disease	0/115 (0%)		1/112 (0.9%)
Myocardial infarction	1/115 (0.9%)		0/112 (0%)
Palpitations	0/115 (0%)		2/112 (1.8%)
Sinus bradycardia	1/115 (0.9%)		0/112 (0%)
Sinus tachycardia	9/115 (7.8%)		3/112 (2.7%)
Ear and labyrinth disorders
Ear and labyrinth disorders-Other	1/115 (0.9%)		2/112 (1.8%)
Ear pain	1/115 (0.9%)		0/112 (0%)
Hearing impaired	4/115 (3.5%)		7/112 (6.3%)
Tinnitus	18/115 (15.7%)		25/112 (22.3%)
Vestibular disorder	1/115 (0.9%)		1/112 (0.9%)
Endocrine disorders
Hyperthyroidism	0/115 (0%)		1/112 (0.9%)
Eye disorders
Blurred vision	6/115 (5.2%)		6/112 (5.4%)
Conjunctivitis	1/115 (0.9%)		0/112 (0%)
Dry eye	0/115 (0%)		1/112 (0.9%)
Eye disorders-Other	0/115 (0%)		2/112 (1.8%)
Photophobia	0/115 (0%)		1/112 (0.9%)
Watering eyes	0/115 (0%)		8/112 (7.1%)
Gastrointestinal disorders
Abdominal pain	12/115 (10.4%)		10/112 (8.9%)
Anal hemorrhage	1/115 (0.9%)		0/112 (0%)
Anal pain	0/115 (0%)		1/112 (0.9%)
Bloating	0/115 (0%)		2/112 (1.8%)
Constipation	47/115 (40.9%)		46/112 (41.1%)
Diarrhea	19/115 (16.5%)		27/112 (24.1%)
Dry mouth	2/115 (1.7%)		4/112 (3.6%)
Dyspepsia	6/115 (5.2%)		10/112 (8.9%)
Dysphagia	2/115 (1.7%)		2/112 (1.8%)
Esophageal pain	0/115 (0%)		2/112 (1.8%)
Esophagitis	0/115 (0%)		2/112 (1.8%)
Flatulence	1/115 (0.9%)		0/112 (0%)
Gastroesophageal reflux disease	11/115 (9.6%)		16/112 (14.3%)
Gastrointestinal disorders-Other	4/115 (3.5%)		4/112 (3.6%)
Gastroparesis	1/115 (0.9%)		0/112 (0%)
Hemorrhoidal hemorrhage	1/115 (0.9%)		0/112 (0%)
Hemorrhoids	0/115 (0%)		1/112 (0.9%)
Mucositis oral	12/115 (10.4%)		39/112 (34.8%)
Nausea	65/115 (56.5%)		72/112 (64.3%)
Oral dysesthesia	0/115 (0%)		2/112 (1.8%)
Oral pain	1/115 (0.9%)		4/112 (3.6%)
Stomach pain	1/115 (0.9%)		1/112 (0.9%)
Toothache	0/115 (0%)		2/112 (1.8%)
Vomiting	18/115 (15.7%)		28/112 (25%)
General disorders
Chills	4/115 (3.5%)		4/112 (3.6%)
Edema face	0/115 (0%)		2/112 (1.8%)
Edema limbs	16/115 (13.9%)		13/112 (11.6%)
Fatigue	82/115 (71.3%)		77/112 (68.8%)
Fever	12/115 (10.4%)		5/112 (4.5%)
Flu like symptoms	5/115 (4.3%)		1/112 (0.9%)
General disorders and admin site conditions - Other	4/115 (3.5%)		4/112 (3.6%)
Infusion related reaction	1/115 (0.9%)		1/112 (0.9%)
Infusion site extravasation	1/115 (0.9%)		0/112 (0%)
Injection site reaction	4/115 (3.5%)		1/112 (0.9%)
Irritability	1/115 (0.9%)		0/112 (0%)
Localized edema	1/115 (0.9%)		1/112 (0.9%)
Malaise	2/115 (1.7%)		2/112 (1.8%)
Non-cardiac chest pain	4/115 (3.5%)		3/112 (2.7%)
Pain	7/115 (6.1%)		8/112 (7.1%)
Immune system disorders
Allergic reaction	1/115 (0.9%)		0/112 (0%)
Infections and infestations
Bladder infection	1/115 (0.9%)		1/112 (0.9%)
Bronchial infection	0/115 (0%)		1/112 (0.9%)
Enterocolitis infectious	0/115 (0%)		2/112 (1.8%)
Eye infection	0/115 (0%)		1/112 (0.9%)
Infections and infestations-Other	2/115 (1.7%)		5/112 (4.5%)
Kidney infection	1/115 (0.9%)		0/112 (0%)
Lung infection	1/115 (0.9%)		1/112 (0.9%)
Mucosal infection	0/115 (0%)		1/112 (0.9%)
Phlebitis infective	2/115 (1.7%)		0/112 (0%)
Rash pustular	1/115 (0.9%)		0/112 (0%)
Sepsis	1/115 (0.9%)		1/112 (0.9%)
Sinusitis	0/115 (0%)		2/112 (1.8%)
Skin infection	2/115 (1.7%)		3/112 (2.7%)
Tooth infection	1/115 (0.9%)		0/112 (0%)
Upper respiratory infection	3/115 (2.6%)		2/112 (1.8%)
Urinary tract infection	17/115 (14.8%)		11/112 (9.8%)
Injury, poisoning and procedural complications
Bruising	4/115 (3.5%)		2/112 (1.8%)
Fall	1/115 (0.9%)		1/112 (0.9%)
Investigations
Alanine aminotransferase increased	10/115 (8.7%)		8/112 (7.1%)
Alkaline phosphatase increased	16/115 (13.9%)		23/112 (20.5%)
Aspartate aminotransferase increased	6/115 (5.2%)		7/112 (6.3%)
Blood bilirubin increased	0/115 (0%)		1/112 (0.9%)
Cholesterol high	0/115 (0%)		2/112 (1.8%)
Creatinine increased	34/115 (29.6%)		37/112 (33%)
Hemoglobin increased	1/115 (0.9%)		1/112 (0.9%)
Investigations-Other	4/115 (3.5%)		3/112 (2.7%)
Lymphocyte count decreased	18/115 (15.7%)		16/112 (14.3%)
Neutrophil count decreased	44/115 (38.3%)		15/112 (13.4%)
Platelet count decreased	50/115 (43.5%)		37/112 (33%)
Weight gain	5/115 (4.3%)		0/112 (0%)
Weight loss	11/115 (9.6%)		11/112 (9.8%)
White blood cell decreased	42/115 (36.5%)		14/112 (12.5%)
Metabolism and nutrition disorders
Anorexia	28/115 (24.3%)		35/112 (31.3%)
Dehydration	10/115 (8.7%)		9/112 (8%)
Glucose intolerance	1/115 (0.9%)		1/112 (0.9%)
Hypercalcemia	1/115 (0.9%)		0/112 (0%)
Hyperglycemia	25/115 (21.7%)		29/112 (25.9%)
Hyperkalemia	10/115 (8.7%)		10/112 (8.9%)
Hypermagnesemia	1/115 (0.9%)		1/112 (0.9%)
Hypernatremia	0/115 (0%)		1/112 (0.9%)
Hypertriglyceridemia	0/115 (0%)		3/112 (2.7%)
Hypoalbuminemia	13/115 (11.3%)		24/112 (21.4%)
Hypocalcemia	9/115 (7.8%)		16/112 (14.3%)
Hypoglycemia	3/115 (2.6%)		2/112 (1.8%)
Hypokalemia	11/115 (9.6%)		20/112 (17.9%)
Hypomagnesemia	35/115 (30.4%)		38/112 (33.9%)
Hyponatremia	25/115 (21.7%)		29/112 (25.9%)
Hypophosphatemia	9/115 (7.8%)		7/112 (6.3%)
Metabolism and nutrition disorders - Other, specify	1/115 (0.9%)		3/112 (2.7%)
Obesity	1/115 (0.9%)		0/112 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/115 (7.8%)		13/112 (11.6%)
Arthritis	1/115 (0.9%)		0/112 (0%)
Back pain	10/115 (8.7%)		10/112 (8.9%)
Bone pain	11/115 (9.6%)		8/112 (7.1%)
Flank pain	2/115 (1.7%)		1/112 (0.9%)
Generalized muscle weakness	11/115 (9.6%)		9/112 (8%)
Muscle weakness lower limb	1/115 (0.9%)		1/112 (0.9%)
Musculoskeletal and connective tiss disorder - Other	1/115 (0.9%)		2/112 (1.8%)
Myalgia	5/115 (4.3%)		4/112 (3.6%)
Neck pain	1/115 (0.9%)		1/112 (0.9%)
Pain in extremity	11/115 (9.6%)		7/112 (6.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	0/115 (0%)		1/112 (0.9%)
Nervous system disorders
Amnesia	0/115 (0%)		1/112 (0.9%)
Concentration impairment	1/115 (0.9%)		1/112 (0.9%)
Dizziness	15/115 (13%)		17/112 (15.2%)
Dysgeusia	19/115 (16.5%)		24/112 (21.4%)
Headache	18/115 (15.7%)		19/112 (17%)
Memory impairment	1/115 (0.9%)		2/112 (1.8%)
Nervous system disorders-Other	2/115 (1.7%)		0/112 (0%)
Paresthesia	1/115 (0.9%)		3/112 (2.7%)
Peripheral motor neuropathy	3/115 (2.6%)		2/112 (1.8%)
Peripheral sensory neuropathy	11/115 (9.6%)		14/112 (12.5%)
Presyncope	2/115 (1.7%)		0/112 (0%)
Sinus pain	0/115 (0%)		2/112 (1.8%)
Somnolence	3/115 (2.6%)		4/112 (3.6%)
Stroke	1/115 (0.9%)		0/112 (0%)
Syncope	3/115 (2.6%)		2/112 (1.8%)
Tremor	3/115 (2.6%)		2/112 (1.8%)
Psychiatric disorders
Agitation	0/115 (0%)		1/112 (0.9%)
Anxiety	13/115 (11.3%)		3/112 (2.7%)
Confusion	0/115 (0%)		1/112 (0.9%)
Depression	7/115 (6.1%)		3/112 (2.7%)
Insomnia	23/115 (20%)		16/112 (14.3%)
Libido decreased	1/115 (0.9%)		0/112 (0%)
Psychiatric disorders-Other	0/115 (0%)		1/112 (0.9%)
Renal and urinary disorders
Acute kidney injury	6/115 (5.2%)		7/112 (6.3%)
Bladder spasm	2/115 (1.7%)		2/112 (1.8%)
Chronic kidney disease	6/115 (5.2%)		3/112 (2.7%)
Cystitis noninfective	3/115 (2.6%)		0/112 (0%)
Hematuria	17/115 (14.8%)		13/112 (11.6%)
Proteinuria	4/115 (3.5%)		2/112 (1.8%)
Renal and urinary disorders-Other	4/115 (3.5%)		3/112 (2.7%)
Urinary frequency	14/115 (12.2%)		4/112 (3.6%)
Urinary incontinence	1/115 (0.9%)		1/112 (0.9%)
Urinary retention	1/115 (0.9%)		0/112 (0%)
Urinary tract obstruction	1/115 (0.9%)		2/112 (1.8%)
Urinary tract pain	7/115 (6.1%)		8/112 (7.1%)
Urinary urgency	2/115 (1.7%)		1/112 (0.9%)
Reproductive system and breast disorders
Dyspareunia	1/115 (0.9%)		0/112 (0%)
Erectile dysfunction	1/115 (0.9%)		0/112 (0%)
Pelvic pain	3/115 (2.6%)		3/112 (2.7%)
Prostatic obstruction	0/115 (0%)		1/112 (0.9%)
Reproductive system and breast disorders - Other	1/115 (0.9%)		0/112 (0%)
Scrotal pain	1/115 (0.9%)		0/112 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	3/115 (2.6%)		1/112 (0.9%)
Bronchospasm	0/115 (0%)		1/112 (0.9%)
Cough	7/115 (6.1%)		10/112 (8.9%)
Dyspnea	13/115 (11.3%)		6/112 (5.4%)
Epistaxis	4/115 (3.5%)		11/112 (9.8%)
Hiccups	13/115 (11.3%)		13/112 (11.6%)
Hoarseness	1/115 (0.9%)		2/112 (1.8%)
Laryngeal inflammation	0/115 (0%)		1/112 (0.9%)
Laryngeal mucositis	1/115 (0.9%)		0/112 (0%)
Nasal congestion	0/115 (0%)		5/112 (4.5%)
Pharyngeal mucositis	0/115 (0%)		1/112 (0.9%)
Pleural effusion	0/115 (0%)		1/112 (0.9%)
Pleuritic pain	1/115 (0.9%)		0/112 (0%)
Pneumonitis	1/115 (0.9%)		0/112 (0%)
Postnasal drip	0/115 (0%)		3/112 (2.7%)
Productive cough	2/115 (1.7%)		1/112 (0.9%)
Resp, thoracic and mediastinal disorders - Other	0/115 (0%)		2/112 (1.8%)
Sinus disorder	0/115 (0%)		1/112 (0.9%)
Sneezing	1/115 (0.9%)		0/112 (0%)
Sore throat	3/115 (2.6%)		6/112 (5.4%)
Skin and subcutaneous tissue disorders
Alopecia	19/115 (16.5%)		48/112 (42.9%)
Bullous dermatitis	0/115 (0%)		1/112 (0.9%)
Dry skin	1/115 (0.9%)		0/112 (0%)
Erythema multiforme	0/115 (0%)		2/112 (1.8%)
Hyperhidrosis	0/115 (0%)		1/112 (0.9%)
Nail discoloration	0/115 (0%)		1/112 (0.9%)
Pain of skin	1/115 (0.9%)		1/112 (0.9%)
Photosensitivity	0/115 (0%)		1/112 (0.9%)
Pruritus	4/115 (3.5%)		1/112 (0.9%)
Rash acneiform	2/115 (1.7%)		3/112 (2.7%)
Rash maculo-papular	8/115 (7%)		6/112 (5.4%)
Skin and subcutaneous tissue disorders - Other	4/115 (3.5%)		7/112 (6.3%)
Urticaria	1/115 (0.9%)		0/112 (0%)
Social circumstances
Social circumstances-Other	1/115 (0.9%)		2/112 (1.8%)
Vascular disorders
Flushing	1/115 (0.9%)		0/112 (0%)
Hot flashes	2/115 (1.7%)		3/112 (2.7%)
Hypertension	23/115 (20%)		30/112 (26.8%)
Hypotension	5/115 (4.3%)		2/112 (1.8%)
Phlebitis	2/115 (1.7%)		0/112 (0%)
Superficial thrombophlebitis	2/115 (1.7%)		0/112 (0%)
Thromboembolic event	11/115 (9.6%)		4/112 (3.6%)
Vascular disorders-Other	0/115 (0%)		1/112 (0.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

Name/Title	Genitourinary Committee Statistician
Organization	SWOG Statistics and Data Management Center
Phone	2066674623
Email	mplets@fredhutch.org

Responsible Party:

Southwest Oncology Group

ClinicalTrials.gov Identifier:

NCT02177695

Other Study ID Numbers:

S1314
S1314
NCI-2014-00850
U10CA180888

First Posted:

Jun 30, 2014

Last Update Posted:

Jan 3, 2022

Last Verified:

Dec 1, 2021

S1314, Co-expression Extrapolation (COXEN) Program to Predict Chemotherapy Response in Patients With Bladder Cancer

Study Details

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Primary Outcome Measures

Secondary Outcome Measures

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Exclusion Criteria:

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Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

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Certain Agreements

Results Point of Contact