Paclitaxel and Radiation Therapy With or Without Trastuzumab in Treating Patients Who Have Undergone Surgery for Bladder Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00238420
• Collaborator: Radiation Therapy Oncology Group (Other)
• Enrollment: 70
• Locations: 184
• Arms: 2
• Actual Duration (Months): 201.8
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase I/II trial is studying the side effects of giving paclitaxel together with radiation therapy with or without trastuzumab and to see how well it works to kill any remaining tumor cells in patients who have undergone surgery for bladder cancer. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Paclitaxel may also make tumor cells more sensitive to radiation therapy. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving paclitaxel together with radiation therapy and trastuzumab may kill more tumor cells. Giving these treatments after surgery may kill any remaining tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Bladder Urothelial Carcinoma; Stage I Bladder Cancer AJCC v6 and v7; Stage II Bladder Cancer AJCC v6 and v7; Stage III Bladder Cancer AJCC v6 and v7	Drug: Paclitaxel; Radiation: Radiation Therapy; Biological: Trastuzumab	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the acute toxicity (=< 90 days from protocol treatment start) from chemoradiotherapy including paclitaxel +/- trastuzumab and irradiation in non-cystectomy patients with or without her2/neu overexpression.

SECONDARY OBJECTIVES:

1. To determine the ability of patients with bladder cancer who are non-cystectomy candidates to complete this treatment program.

2. To evaluate the efficacy of this treatment program in achieving a complete response of the primary tumor.

3. To measure the 5-year disease-free and overall survival of patients with bladder cancer treated with transurethral resection of the bladder followed by chemoradiotherapy.

4. To estimate the value of tumor and/or serum biomarkers as predictors of initial tumor response and recurrence-free survival.

OUTLINE: This is a non-randomized, multicenter study. Patients are assigned to 1 of 2 treatment groups according to HER2/neu status (HER2/neu 2+ or 3+ staining [group 1] vs HER2/neu 0 or 1+ staining [group 2]).

GROUP I: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, 36, and 43 and trastuzumab (Herceptin®) IV over 90 minutes on day 1 and then over 30 minutes on days 8, 15, 22, 29, 36, and 43. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50. Treatment continues in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive paclitaxel and undergo radiotherapy as in group 1.

After completion of study treatment, patients are followed at 4-5 weeks, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation Following Transurethral Surgery for Non-Cystectomy Candidates With Muscle-Invasive Bladder Cancer
• Actual Study Start Date: Jul 26, 2005
• Actual Primary Completion Date: Feb 5, 2014
• Actual Study Completion Date: May 20, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group I (paclitaxel, trastuzumab, radiation therapy) Patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, and 43 and trastuzumab IV over 90 minutes on day 1 and then over 30 minutes on days 8, 15, 22, 29, 36, and 43. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50. Treatment continues in the absence of disease progression or unacceptable toxicity.	Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation ; Biological: Trastuzumab; Given IV; Other Names: ABP 980 ALT02 Anti-c-ERB-2 Anti-c-erbB2 Monoclonal Antibody Anti-ERB-2 Anti-erbB-2 Anti-erbB2 Monoclonal Antibody Anti-HER2/c-erbB2 Monoclonal Antibody Anti-p185-HER2 c-erb-2 Monoclonal Antibody HER2 Monoclonal Antibody Herceptin Herceptin Biosimilar PF-05280014 Herceptin Trastuzumab Biosimilar PF-05280014 Herzuma Kanjinti MoAb HER2 Monoclonal Antibody c-erb-2 Monoclonal Antibody HER2 Ogivri Ontruzant PF-05280014 rhuMAb HER2 RO0452317 SB3 Trastuzumab Biosimilar ABP 980 Trastuzumab Biosimilar ALT02 trastuzumab biosimilar EG12014 Trastuzumab Biosimilar HLX02 Trastuzumab Biosimilar PF-05280014 Trastuzumab Biosimilar SB3 Trastuzumab Biosimilar SIBP-01 Trastuzumab-anns Trastuzumab-dkst Trastuzumab-dttb Trastuzumab-pkrb Trastuzumab-qyyp Trazimera
Experimental: Group II (paclitaxel, radiation therapy) Patients receive paclitaxel and undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50.	Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation

Outcome Measures

Primary Outcome Measures

1. Acute Treatment-related Toxicity [From start of protocol treatment to 90 days]

   In each group, the number of patients was tabulated by type and grade (gr) of treatment-related toxicity (CTCAE v3.0). Only the following types of toxicity within 90 days of treatment start were considered: ≥ gr4 neutropenia, ≥ gr4 febrile neutropenia, ≥ gr3 diarrhea, ≥ gr3 nausea/vomiting, ≥ gr3 thrombocytopenia, ≥ gr3 renal, pulmonary, hepatic, or neurologic toxicity, ≥ gr3 rectal or genitourinary bleeding, ≥ gr3 left ventricular failure, or ≥ gr2 other cardiac toxicity. The study was designed to estimate the rate of acute treatment-related toxicity separately in each group of patients. Using the Fleming's one-sample multiple test procedure with Type I and II errors each set at 10%, 40 cases/group were required to reject the null hypothesis that the true toxicity rate is greater than 25% in favor of the alternative hypothesis that the true rate is no more than 10%. Six or more patients with the designated toxicities out of 40 would result in rejecting the null hypothesis.

Secondary Outcome Measures

1. Treatment Completion [From registration to end of treatment; up to 64 days."]

   The number of patients within each group who completed all elements of protocol treatment are reported.

2. Complete Response to Treatment [At 12 weeks from treatment start]

   The number of patients within each group who achieved a complete response to protocol treatment by 12 weeks are reported. Complete response is defined as no gross tumor at cystoscopy or negative biopsies or both by week 12 after completion of protocol treatment.

3. Progression-free Survival [From start of treatment to last follow-up. Maximum follow-up at time of analysis was 9.9 years.]

   Disease (failure) is defined as any bladder cancer progression determined by all measures of disease including physical exam, imaging, and biopsies. Disease-free survival time is defined as time from treatment start to the date of first progression, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method. Analysis occurred after all patients had been on study for at least 5 years. This is a non-randomized phase I/II trial in which the two patient groups are not compared.

4. Overall Survival [From the date of treatment started to death, assessed up to at least 5 years]

   Overall survival time is defined as time from treatment start to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated using the Kaplan-Meier method. Analysis occurred after all patients had been on study for at least 5 years. This is a non-randomized phase I/II trial in which the two patient groups are not compared.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed primary transitional cell carcinoma (TCC) of the bladder

• Histologic evidence of muscularis propria invasion

• Meets 1 of the following stage criteria:

• Stage T2-4a; NX, N0, or N1; and M0 disease

• Clinical stage T1, grade 3/3 disease AND requires definitive local therapy

• Tumor involvement of the prostatic urethra allowed provided the following criteria are met:

• Tumor was visibly completely resected

• No evidence of stromal invasion of the prostate

• No evidence of distant metastases by chest x-ray (or chest CT scan) within 8 weeks prior to registration

• No evidence of distant metastases by abdominal/pelvic CT scan (or MRI scan) within 8 weeks prior to registration

• Has undergone transurethral bladder resection (as thorough as is judged safely possible) within the past 3-8 weeks, including bimanual examination with tumor mapping

• Sufficient tumor tissue available for HER2/neu analysis

• Not a candidate for radical cystectomy

• Performance status - Zubrod 0-2

• Absolute neutrophil count >= 1,800/mm^3

• Platelet count >= 100,000/mm^3

• Hemoglobin >= 8.0 g/dL (transfusion or other intervention allowed)

• Bilirubin < 2.0 mg/dL

• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 times upper limit of normal

• No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

• Creatinine =< 3.0 mg/dL

• Left ventricular ejection fraction (LVEF) >= 40% by multigated acquisition scan (MUGA) scan or echocardiogram

• No unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months

• No transmural myocardial infarction within the past 6 months

• Not pregnant or nursing

• No nursing for 6 months after completion of study treatment (for patients receiving trastuzumab [Herceptin®])

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 6 months after completion of study treatment

• Able to tolerate systemic chemotherapy and pelvic radiotherapy

• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer

• No history of allergic reaction to study drugs

• No history of inflammatory bowel disease

• No acute bacterial or fungal infection requiring IV antibiotics

• No AIDS

• No other severe active comorbidity

• No prior systemic chemotherapy with anthracyclines or taxanes

• No prior systemic chemotherapy for TCC

• No prior pelvic radiotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mobile Infirmary Medical Center	Mobile	Alabama	United States	36607
2	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
3	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California	United States	95603
4	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
5	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California	United States	95682
6	Mercy San Juan Medical Center	Carmichael	California	United States	95608
7	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California	United States	95661
8	Sutter Medical Center Sacramento	Sacramento	California	United States	95816
9	Mercy General Hospital Radiation Oncology Center	Sacramento	California	United States	95819
10	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California	United States	95687
11	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
12	The Reverend Roger Patrick Dorcy Cancer Center at Saint Mary-Corwin Medical Center	Pueblo	Colorado	United States	81004
13	Beebe Medical Center	Lewes	Delaware	United States	19958
14	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
15	Saint Francis Hospital - Wilmington	Wilmington	Delaware	United States	19805
16	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
17	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
18	University of Florida Health Science Center - Jacksonville	Jacksonville	Florida	United States	32209
19	Jupiter Medical Center	Jupiter	Florida	United States	33458
20	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
21	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
22	Orlando Health Cancer Institute	Orlando	Florida	United States	32806
23	Bay Medical Center	Panama City	Florida	United States	32401
24	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
25	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
26	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
27	Graham Hospital Association	Canton	Illinois	United States	61520
28	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
29	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
30	Memorial Hospital	Carthage	Illinois	United States	62321
31	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
32	Heartland Cancer Research NCORP	Decatur	Illinois	United States	62526
33	Eureka Hospital	Eureka	Illinois	United States	61530
34	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
35	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
36	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
37	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
38	Illinois CancerCare-Havana	Havana	Illinois	United States	62644
39	Mason District Hospital	Havana	Illinois	United States	62644
40	Hopedale Medical Complex - Hospital	Hopedale	Illinois	United States	61747
41	Duly Health and Care Joliet	Joliet	Illinois	United States	60435
42	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
43	Kewanee Hospital	Kewanee	Illinois	United States	61443
44	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
45	Mcdonough District Hospital	Macomb	Illinois	United States	61455
46	Holy Family Medical Center	Monmouth	Illinois	United States	61462
47	Illinois CancerCare-Monmouth	Monmouth	Illinois	United States	61462
48	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
49	Carle Cancer Institute Normal	Normal	Illinois	United States	61761
50	Illinois CancerCare-Community Cancer Center	Normal	Illinois	United States	61761
51	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
52	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
53	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
54	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
55	Pekin Hospital	Pekin	Illinois	United States	61554
56	Proctor Hospital	Peoria	Illinois	United States	61614
57	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
58	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois	United States	61615
59	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
60	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
61	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
62	Illinois Valley Hospital	Peru	Illinois	United States	61354
63	Valley Radiation Oncology	Peru	Illinois	United States	61354
64	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
65	Perry Memorial Hospital	Princeton	Illinois	United States	61356
66	Illinois CancerCare-Spring Valley	Spring Valley	Illinois	United States	61362
67	Saint Margaret's Hospital	Spring Valley	Illinois	United States	61362
68	Memorial Medical Center	Springfield	Illinois	United States	62781
69	Carle Cancer Center	Urbana	Illinois	United States	61801
70	Radiation Oncology Associates PC	Fort Wayne	Indiana	United States	46804
71	Parkview Hospital Randallia	Fort Wayne	Indiana	United States	46805
72	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
73	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
74	Mercy Capitol	Des Moines	Iowa	United States	50307
75	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
76	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa	United States	50309
77	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
78	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
79	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
80	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
81	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
82	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51102
83	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
84	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
85	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
86	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
87	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
88	Southwest Medical Center	Liberal	Kansas	United States	67901
89	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
90	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
91	Associates In Womens Health	Wichita	Kansas	United States	67208
92	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
93	Ascension Via Christi Hospitals Wichita	Wichita	Kansas	United States	67214
94	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
95	Wesley Medical Center	Wichita	Kansas	United States	67214
96	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
97	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
98	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
99	Christiana Care - Union Hospital	Elkton	Maryland	United States	21921
100	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
101	Boston Medical Center	Boston	Massachusetts	United States	02118
102	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
103	Saint Anne's Hospital	Fall River	Massachusetts	United States	02721
104	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
105	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
106	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
107	Borgess Medical Center	Kalamazoo	Michigan	United States	49048
108	Singing River Hospital	Pascagoula	Mississippi	United States	39581
109	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
110	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
111	Billings Clinic Cancer Center	Billings	Montana	United States	59101
112	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
113	Montana Cancer Consortium NCORP	Billings	Montana	United States	59102
114	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
115	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
116	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana	United States	59405
117	Great Falls Clinic	Great Falls	Montana	United States	59405
118	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
119	Nevada Cancer Institute-Summerlin Campus	Las Vegas	Nevada	United States	89135
120	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada	United States	89169
121	Cheshire Medical Center-Dartmouth-Hitchcock Keene	Keene	New Hampshire	United States	03431
122	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
123	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
124	Virtua Memorial	Mount Holly	New Jersey	United States	08060
125	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
126	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
127	Inspira Medical Center Vineland	Vineland	New Jersey	United States	08360
128	Hudson Valley Oncology Associates	Poughkeepsie	New York	United States	12601
129	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
130	Vidant Oncology-Kinston	Kinston	North Carolina	United States	28501
131	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
132	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
133	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
134	Summa Health System - Akron Campus	Akron	Ohio	United States	44304
135	Cleveland Clinic Akron General	Akron	Ohio	United States	44307
136	Summa Health System - Barberton Campus	Barberton	Ohio	United States	44203
137	Cleveland Clinic Mercy Hospital	Canton	Ohio	United States	44708
138	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
139	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
140	UH Seidman Cancer Center at Salem Regional Medical Center	Salem	Ohio	United States	44460
141	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
142	Cancer Treatment Center	Wooster	Ohio	United States	44691
143	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
144	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
145	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
146	Providence Portland Medical Center	Portland	Oregon	United States	97213
147	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
148	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
149	Northeast Radiation Oncology Center	Dunmore	Pennsylvania	United States	18512
150	Fox Chase Cancer Center Buckingham	Furlong	Pennsylvania	United States	18925
151	Riddle Memorial Hospital	Media	Pennsylvania	United States	19063
152	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
153	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
154	Lankenau Medical Center	Wynnewood	Pennsylvania	United States	19096
155	Main Line Health NCORP	Wynnewood	Pennsylvania	United States	19096
156	Medical University of South Carolina	Charleston	South Carolina	United States	29425
157	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
158	Sandra L Maxwell Cancer Center	Cedar City	Utah	United States	84720
159	Logan Regional Hospital	Logan	Utah	United States	84321
160	Cottonwood Hospital Medical Center	Murray	Utah	United States	84107
161	Intermountain Medical Center	Murray	Utah	United States	84107
162	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
163	Utah Valley Regional Medical Center	Provo	Utah	United States	84604
164	Saint George Regional Medical Center	Saint George	Utah	United States	84770
165	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah	United States	84106
166	LDS Hospital	Salt Lake City	Utah	United States	84143
167	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont	United States	05819
168	Danville Regional Medical Center	Danville	Virginia	United States	24541
169	Saint Francis Hospital	Federal Way	Washington	United States	98003
170	EvergreenHealth Medical Center	Kirkland	Washington	United States	98033
171	MultiCare Good Samaritan Hospital	Puyallup	Washington	United States	98372
172	Valley Medical Center	Renton	Washington	United States	98055
173	Virginia Mason Medical Center	Seattle	Washington	United States	98101
174	MultiCare Tacoma General Hospital	Tacoma	Washington	United States	98405
175	Northwest NCI Community Oncology Research Program	Tacoma	Washington	United States	98405
176	Saint Joseph Medical Center	Tacoma	Washington	United States	98405
177	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
178	Compass Oncology Vancouver	Vancouver	Washington	United States	98684
179	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
180	Welch Cancer Center	Sheridan	Wyoming	United States	82801
181	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
182	Atlantic Health Sciences Corporation-Saint John Regional Hospital	Saint John	New Brunswick	Canada	E2L 4L2
183	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
184	McGill University Department of Oncology	Montreal	Quebec	Canada	H2W 1S6

Sponsors and Collaborators

• National Cancer Institute (NCI)
• Radiation Therapy Oncology Group

Investigators

• Principal Investigator: M. D Michaelson, Radiation Therapy Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00238420
• Other Study ID Numbers: NCI-2009-00730; NCI-2009-00730; RTOG-0524; CDR0000440988; RTOG 0524; RTOG-0524; U10CA180868; U10CA021661
• First Posted: Oct 13, 2005
• Last Update Posted: Jul 19, 2022
• Last Verified: May 1, 2022

• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Paclitaxel; Trastuzumab; Albumin-Bound Paclitaxel; Trastuzumab biosimilar HLX02; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Pre-assignment Detail	After patient registration, sites submitted tissue to central her2/neu evaluation. If tissue was evaluable and a patient continued on study, then treatment arm was assigned. Seventy-six patients were registered and 6 did not continue to treatment assignment: 2 patient withdrawal, 2 protocol violation, 1 progressive disease, 1 institutional error.

Arm/Group Title	HER2+ :RT, Paclitaxel, and Trastuzumab	HER2- :RT and Paclitaxel
Arm/Group Description	Paclitaxel and trastuzumab chemotherapy with concurrent with radiation therapy	Paclitaxel chemotherapy concurrent with radiation therapy
Period Title: Overall Study
STARTED	22	48
COMPLETED	21	47
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	HER2+ :RT, Paclitaxel, and Trastuzumab	HER2- :RT and Paclitaxel	Total
Arm/Group Description	Paclitaxel and trastuzumab chemotherapy with concurrent with radiation therapy	Paclitaxel chemotherapy concurrent with radiation therapy	Total of all reporting groups
Overall Participants	21	47	68
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	80	73	75
Sex: Female, Male (Count of Participants)
Female	2 9.5%	11 23.4%	13 19.1%
Male	19 90.5%	36 76.6%	55 80.9%

Outcome Measures

1. Primary Outcome

Title	Acute Treatment-related Toxicity
Description	In each group, the number of patients was tabulated by type and grade (gr) of treatment-related toxicity (CTCAE v3.0). Only the following types of toxicity within 90 days of treatment start were considered: ≥ gr4 neutropenia, ≥ gr4 febrile neutropenia, ≥ gr3 diarrhea, ≥ gr3 nausea/vomiting, ≥ gr3 thrombocytopenia, ≥ gr3 renal, pulmonary, hepatic, or neurologic toxicity, ≥ gr3 rectal or genitourinary bleeding, ≥ gr3 left ventricular failure, or ≥ gr2 other cardiac toxicity. The study was designed to estimate the rate of acute treatment-related toxicity separately in each group of patients. Using the Fleming's one-sample multiple test procedure with Type I and II errors each set at 10%, 40 cases/group were required to reject the null hypothesis that the true toxicity rate is greater than 25% in favor of the alternative hypothesis that the true rate is no more than 10%. Six or more patients with the designated toxicities out of 40 would result in rejecting the null hypothesis.
Time Frame	From start of protocol treatment to 90 days

Outcome Measure Data

Analysis Population Description

All eligible patients who started study treatment

Arm/Group Title	HER2+ :RT, Paclitaxel, and Trastuzumab	HER2- :RT and Paclitaxel
Arm/Group Description	Paclitaxel and trastuzumab chemotherapy with concurrent with radiation therapy	Paclitaxel chemotherapy concurrent with radiation therapy
Measure Participants	21	47
Number [participants]	7 33.3%	14 29.8%

2. Secondary Outcome

Title	Treatment Completion
Description	The number of patients within each group who completed all elements of protocol treatment are reported.
Time Frame	From registration to end of treatment; up to 64 days."

Outcome Measure Data

Analysis Population Description

All eligible patients who started study treatment

Arm/Group Title	HER2+ :RT, Paclitaxel, and Trastuzumab	HER2- :RT and Paclitaxel
Arm/Group Description	Paclitaxel and trastuzumab chemotherapy with concurrent with radiation therapy	Paclitaxel chemotherapy concurrent with radiation therapy
Measure Participants	21	47
Number [participants]	13 61.9%	34 72.3%

3. Secondary Outcome

Title	Complete Response to Treatment
Description	The number of patients within each group who achieved a complete response to protocol treatment by 12 weeks are reported. Complete response is defined as no gross tumor at cystoscopy or negative biopsies or both by week 12 after completion of protocol treatment.
Time Frame	At 12 weeks from treatment start

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment and had an evaluation to assess response by 12 weeks

Arm/Group Title	HER2+ :RT, Paclitaxel, and Trastuzumab	HER2- :RT and Paclitaxel
Arm/Group Description	Paclitaxel and trastuzumab chemotherapy with concurrent with radiation therapy	Paclitaxel chemotherapy concurrent with radiation therapy
Measure Participants	13	33
Number (95% Confidence Interval) [percentage of participants]	61.5 292.9%	57.6 122.6%

4. Secondary Outcome

Title	Progression-free Survival
Description	Disease (failure) is defined as any bladder cancer progression determined by all measures of disease including physical exam, imaging, and biopsies. Disease-free survival time is defined as time from treatment start to the date of first progression, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method. Analysis occurred after all patients had been on study for at least 5 years. This is a non-randomized phase I/II trial in which the two patient groups are not compared.
Time Frame	From start of treatment to last follow-up. Maximum follow-up at time of analysis was 9.9 years.

Outcome Measure Data

Analysis Population Description

Eligible participants who started treatment. (This population changed since the initial analysis: 3 participants first thought to be eligible were later determined to be ineligible.)

Arm/Group Title	HER2+ :RT, Paclitaxel, and Trastuzumab	HER2- :RT and Paclitaxel
Arm/Group Description	Paclitaxel and trastuzumab chemotherapy with concurrent with radiation therapy	Paclitaxel chemotherapy concurrent with radiation therapy
Measure Participants	20	45
Median (95% Confidence Interval) [years]	1.1	0.8

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival time is defined as time from treatment start to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated using the Kaplan-Meier method. Analysis occurred after all patients had been on study for at least 5 years. This is a non-randomized phase I/II trial in which the two patient groups are not compared.
Time Frame	From the date of treatment started to death, assessed up to at least 5 years

Outcome Measure Data

Analysis Population Description

Eligible participants who started treatment. (This population changed since the initial analysis: 3 participants first thought to be eligible were later determined to be ineligible.)

Arm/Group Title	HER2+ :RT, Paclitaxel, and Trastuzumab	HER2- :RT and Paclitaxel
Arm/Group Description	Paclitaxel and trastuzumab chemotherapy with concurrent with radiation therapy	Paclitaxel chemotherapy concurrent with radiation therapy
Measure Participants	20	45
Median (95% Confidence Interval) [years]	2.8	2.0

Adverse Events

Adverse Event Reporting Description	Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events.
Arm/Group Title	HER2+ :RT, Paclitaxel, and Trastuzumab		HER2- :RT and Paclitaxel
Arm/Group Description	Paclitaxel and trastuzumab chemotherapy with concurrent with radiation therapy		Paclitaxel chemotherapy concurrent with radiation therapy
All Cause Mortality
	HER2+ :RT, Paclitaxel, and Trastuzumab		HER2- :RT and Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	HER2+ :RT, Paclitaxel, and Trastuzumab		HER2- :RT and Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/21 (28.6%)		15/47 (31.9%)
Blood and lymphatic system disorders
Hemoglobin	0/21 (0%)		1/47 (2.1%)
Cardiac disorders
Myocardial ischemia	0/21 (0%)		1/47 (2.1%)
Sinus bradycardia	0/21 (0%)		1/47 (2.1%)
Supraventricular arrhythmia NOS	1/21 (4.8%)		0/47 (0%)
Gastrointestinal disorders
Abdominal pain NOS	0/21 (0%)		1/47 (2.1%)
Colonic perforation	1/21 (4.8%)		0/47 (0%)
Diarrhea NOS	4/21 (19%)		3/47 (6.4%)
Enteritis	0/21 (0%)		1/47 (2.1%)
Proctitis NOS	1/21 (4.8%)		0/47 (0%)
Vomiting NOS	0/21 (0%)		1/47 (2.1%)
General disorders
Edema: limb	1/21 (4.8%)		0/47 (0%)
Pyrexia	0/21 (0%)		2/47 (4.3%)
Sudden death	0/21 (0%)		1/47 (2.1%)
Hepatobiliary disorders
Hepatobiliary/pancreas - Other	0/21 (0%)		1/47 (2.1%)
Infections and infestations
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Urinary tract NOS	0/21 (0%)		1/47 (2.1%)
Kidney infection NOS	0/21 (0%)		1/47 (2.1%)
Pneumonia NOS	0/21 (0%)		1/47 (2.1%)
Urinary tract infection NOS	1/21 (4.8%)		2/47 (4.3%)
Injury, poisoning and procedural complications
Vascular access NOS complication	0/21 (0%)		2/47 (4.3%)
Investigations
Leukopenia NOS	0/21 (0%)		1/47 (2.1%)
Lymphopenia	1/21 (4.8%)		0/47 (0%)
Metabolism and nutrition disorders
Dehydration	0/21 (0%)		2/47 (4.3%)
Hypoalbuminemia	1/21 (4.8%)		0/47 (0%)
Hyponatremia	1/21 (4.8%)		0/47 (0%)
Psychiatric disorders
Confusional state	0/21 (0%)		1/47 (2.1%)
Personality change	0/21 (0%)		1/47 (2.1%)
Renal and urinary disorders
Bladder pain	1/21 (4.8%)		0/47 (0%)
Ureteric stenosis	0/21 (0%)		1/47 (2.1%)
Urethral pain	0/21 (0%)		1/47 (2.1%)
Respiratory, thoracic and mediastinal disorders
Aspiration	1/21 (4.8%)		0/47 (0%)
Dyspnea	0/21 (0%)		1/47 (2.1%)
Pneumonitis NOS	0/21 (0%)		1/47 (2.1%)
Vascular disorders
Hematoma	1/21 (4.8%)		0/47 (0%)
Hypotension NOS	1/21 (4.8%)		0/47 (0%)
Thrombosis	0/21 (0%)		1/47 (2.1%)
Other (Not Including Serious) Adverse Events
	HER2+ :RT, Paclitaxel, and Trastuzumab		HER2- :RT and Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/21 (95.2%)		46/47 (97.9%)
Blood and lymphatic system disorders
Blood/bone marrow - Other	3/21 (14.3%)		3/47 (6.4%)
Hemoglobin	15/21 (71.4%)		25/47 (53.2%)
Cardiac disorders
Atrial fibrillation	2/21 (9.5%)		1/47 (2.1%)
Gastrointestinal disorders
Abdominal pain NOS	2/21 (9.5%)		7/47 (14.9%)
Constipation	4/21 (19%)		12/47 (25.5%)
Diarrhea NOS	12/21 (57.1%)		37/47 (78.7%)
Flatulence	1/21 (4.8%)		3/47 (6.4%)
Nausea	5/21 (23.8%)		16/47 (34%)
Proctitis NOS	3/21 (14.3%)		2/47 (4.3%)
Rectal hemorrhage	2/21 (9.5%)		4/47 (8.5%)
Stomatitis	0/21 (0%)		3/47 (6.4%)
Vomiting NOS	4/21 (19%)		10/47 (21.3%)
General disorders
Edema: limb	4/21 (19%)		12/47 (25.5%)
Fatigue	15/21 (71.4%)		39/47 (83%)
Pain - Other	2/21 (9.5%)		2/47 (4.3%)
Pyrexia	0/21 (0%)		4/47 (8.5%)
Infections and infestations
Infection with unknown ANC: Urinary tract NOS	2/21 (9.5%)		1/47 (2.1%)
Opportunisitic infection	2/21 (9.5%)		1/47 (2.1%)
Urinary tract infection NOS	1/21 (4.8%)		6/47 (12.8%)
Injury, poisoning and procedural complications
Dermatitis radiation NOS	1/21 (4.8%)		7/47 (14.9%)
Investigations
Alanine aminotransferase increased	4/21 (19%)		1/47 (2.1%)
Aspartate aminotransferase increased	2/21 (9.5%)		1/47 (2.1%)
Blood alkaline phosphatase increased	3/21 (14.3%)		2/47 (4.3%)
Blood bilirubin increased	2/21 (9.5%)		2/47 (4.3%)
Blood creatinine increased	6/21 (28.6%)		13/47 (27.7%)
Leukopenia NOS	10/21 (47.6%)		15/47 (31.9%)
Lymphopenia	8/21 (38.1%)		10/47 (21.3%)
Metabolic/laboratory - Other	3/21 (14.3%)		1/47 (2.1%)
Neutrophil count	5/21 (23.8%)		4/47 (8.5%)
Platelet count decreased	5/21 (23.8%)		10/47 (21.3%)
Prothrombin time prolonged	2/21 (9.5%)		2/47 (4.3%)
Weight decreased	4/21 (19%)		12/47 (25.5%)
Metabolism and nutrition disorders
Anorexia	8/21 (38.1%)		14/47 (29.8%)
Dehydration	4/21 (19%)		5/47 (10.6%)
Hyperglycemia NOS	6/21 (28.6%)		11/47 (23.4%)
Hyperkalemia	2/21 (9.5%)		3/47 (6.4%)
Hypoalbuminemia	5/21 (23.8%)		7/47 (14.9%)
Hypocalcemia	4/21 (19%)		10/47 (21.3%)
Hypokalemia	1/21 (4.8%)		7/47 (14.9%)
Hyponatremia	4/21 (19%)		15/47 (31.9%)
Musculoskeletal and connective tissue disorders
Back pain	2/21 (9.5%)		7/47 (14.9%)
Bone pain	1/21 (4.8%)		3/47 (6.4%)
Muscle weakness NOS	0/21 (0%)		3/47 (6.4%)
Pain in extremity	1/21 (4.8%)		3/47 (6.4%)
Nervous system disorders
Dizziness	1/21 (4.8%)		6/47 (12.8%)
Dysgeusia	1/21 (4.8%)		5/47 (10.6%)
Headache	0/21 (0%)		3/47 (6.4%)
Peripheral motor neuropathy	0/21 (0%)		3/47 (6.4%)
Peripheral sensory neuropathy	1/21 (4.8%)		8/47 (17%)
Psychiatric disorders
Anxiety	2/21 (9.5%)		2/47 (4.3%)
Insomnia	4/21 (19%)		1/47 (2.1%)
Renal and urinary disorders
Bladder pain	3/21 (14.3%)		9/47 (19.1%)
Bladder spasm	1/21 (4.8%)		6/47 (12.8%)
Bladder stenosis	2/21 (9.5%)		0/47 (0%)
Cystitis NOS	12/21 (57.1%)		17/47 (36.2%)
Pollakiuria	12/21 (57.1%)		24/47 (51.1%)
Proteinuria	2/21 (9.5%)		0/47 (0%)
Renal/genitourinary - Other	3/21 (14.3%)		2/47 (4.3%)
Ureteric obstruction	1/21 (4.8%)		4/47 (8.5%)
Urethral pain	0/21 (0%)		4/47 (8.5%)
Urinary bladder hemorrhage	4/21 (19%)		9/47 (19.1%)
Urinary incontinence	3/21 (14.3%)		6/47 (12.8%)
Urinary retention	2/21 (9.5%)		4/47 (8.5%)
Reproductive system and breast disorders
Pelvic pain NOS	1/21 (4.8%)		3/47 (6.4%)
Respiratory, thoracic and mediastinal disorders
Cough	2/21 (9.5%)		10/47 (21.3%)
Dyspnea	3/21 (14.3%)		8/47 (17%)
Hypoxia	0/21 (0%)		3/47 (6.4%)
Rhinitis allergic NOS	0/21 (0%)		3/47 (6.4%)
Skin and subcutaneous tissue disorders
Alopecia	0/21 (0%)		7/47 (14.9%)
Dermatitis exfoliative NOS	1/21 (4.8%)		4/47 (8.5%)
Vascular disorders
Hypertension NOS	2/21 (9.5%)		1/47 (2.1%)
Hypotension NOS	2/21 (9.5%)		5/47 (10.6%)

Limitations/Caveats

Accrual of patients with her2/neu overexpression stopped early due to unmet targeted accrual goals, with 22 subject accrued out of 40 planned.

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.