Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00335556
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 291
• Locations: 187
• Arms: 6
• Patients Per Site: 1.6

Study Details

Study Description

Brief Summary

This phase II trial is studying how well combination chemotherapy, radiation therapy, and/or surgery work in treating patients with high-risk kidney tumors. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Condition or Disease	Intervention/Treatment	Phase
Childhood Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; Clear Cell Sarcoma of the Kidney; Papillary Renal Cell Carcinoma; Rhabdoid Tumor of the Kidney; Stage I Renal Cell Cancer; Stage I Renal Wilms Tumor; Stage II Renal Cell Cancer; Stage II Renal Wilms Tumor; Stage III Renal Cell Cancer; Stage III Renal Wilms Tumor; Stage IV Renal Cell Cancer; Stage IV Renal Wilms Tumor	Drug: Doxorubicin Hydrochloride; Drug: Irinotecan Hydrochloride; Procedure: Conventional Surgery; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Carboplatin; Biological: Dactinomycin; Drug: Vincristine Sulfate; Radiation: Radiation Therapy; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Evaluate whether a treatment regimen containing cyclophosphamide, carboplatin, and etoposide alternating with vincristine, doxorubicin hydrochloride, and cyclophosphamide (regimen UH-1) improves the event-free and overall survival of patients with diffuse anaplastic Wilms' tumor (DAWT) as compared to historical controls.

2. Evaluate, in a phase II "window" study, the antitumor activity of a combination of vincristine and protracted-schedule irinotecan hydrochloride in patients with metastatic DAWT.

3. Evaluate whether regimen UH-1 improves the event-free and overall survival of patients with malignant rhabdoid tumor (MRT) as compared to historical controls.

4. Maintain the excellent event-free survival of patients with stage I clear cell sarcoma of the kidney (CCSK) without the use of abdominal irradiation.

SECONDARY OBJECTIVES:

1. Describe the outcomes of patients with stage I DAWT or stages I-III focal anaplastic Wilms' tumor (FAWT) treated with vincristine, dactinomycin, doxorubicin hydrochloride, and flank radiation.

2. Describe the outcomes of patients with stage IV FAWT or stage IV CCSK treated with regimen UH-1.

3. Describe event-free and overall survival of children and adolescents with localized renal cell carcinoma (RCC) (including patients with local lymph node involvement) treated with surgical resection without adjuvant therapy.

4. Describe response rate, event-free survival, and overall survival of patients with unresectable or distantly metastatic RCC treated according to institutional preference.

5. Correlate histologic and molecular cytogenetic findings with outcome in pediatric RCC.

6. Evaluate the frequency of germline and inherited INI1 mutations in renal and extrarenal MRT and correlate the presence of detectable INI1 mutation with clinical outcome.

7. Determine the frequency of TP53 mutations in anaplastic Wilms' tumor and correlate the presence of detectable TP53 mutation with clinical outcome.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 6 treatment regimens according to tumor histology, stage of disease, and response to treatment.

SURGERY (renal cell carcinoma [RCC]): Patients with completely resectable stage I-IV RCC undergo surgical resection. Patients with incompletely resectable stage III-IV RCC undergo treatment as per physician's choice.

REGIMEN UH-1 (stage II-III or stage IV [with no measurable disease] diffuse anaplastic Wilms' tumor [DAWT], stage I-IV malignant rhabdoid tumor [MRT], stage IV focal anaplastic Wilms' tumor [FAWT], or stage IV clear cell sarcoma of the kidney [CCSK]): Patients receive vincristine IV on day 1 in weeks 1-3, 10-12, 13-15, 22-24, and 28-30; doxorubicin hydrochloride IV over 15 minutes on day 1 and cyclophosphamide (CPM2) IV over 15-30 minutes on day 1 in weeks 1, 10, 13, 22, and 28; and cyclophosphamide (at lower doses [CPM1]) IV over 1 hour and etoposide IV over 1 hour on days 1-4 and carboplatin IV over 1 hour on day 1 in weeks 4, 7, 16, 19, and 25. Patients whose primary tumors were initially resected undergo radiotherapy once daily 5 days a week for 4-5½ weeks beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13. Patients with unresectable CCSK receive no further study therapy.

IRINOTECAN/VINCRISTINE WINDOW THERAPY* (stage IV DAWT with measurable disease at diagnosis):

Patients receive vincristine IV on day 1 and irinotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 2. Patients with progressive disease (PD) are treated with regimen UH-1. Patients with stable disease (SD), partial response (PR), or complete response (CR) receive another course of irinotecan hydrochloride/vincristine window therapy beginning on day 22. After the second course, patients with SD or PD are treated with regimen UH-1 and patients with PR or CR are treated with regimen UH-2.

NOTE: *Patients who are eligible for but who are unwilling to receive window therapy, receive therapy on regimen UH-1.

REGIMEN UH-2 (DAWT with CR/PR to irinotecan hydrochloride/vincristine window therapy):

Patients receive vincristine on day 1 in weeks 1-3, 10, 11, 16-21, 25, 26, 28-30, and 34-36 and doxorubicin hydrochloride and CPM2 as in regimen UH-1 in weeks 1, 16, 19, 28, and 34. Patients also receive CPM1, etoposide, and carboplatin as in regimen UH-1 in weeks 4, 7, 13, 22, and 31 and irinotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 10, 11, 25, and 26. Patients whose primary tumors were initially resected undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 7. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 7.

REGIMEN I (stage I-III CCSK): Patients receive vincristine IV on day 1 in weeks 1-3, 5-9, 8-9, 11-14, 19, and 25; doxorubicin hydrochloride IV over 15 minutes on day 1 and cyclophosphamide IV over 1 hour on days 1-3 in weeks 1, 7, 13, 19, and 25; and cyclophosphamide IV and etoposide IV on days 1-5 in weeks 4, 10, 16, and 22. Patients whose primary tumors were initially resected (except those with stage I CCSK) undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13.

REGIMEN DD-4A (stage I DAWT or stages I-III FAWT): Patients receive dactinomycin IV over 1-5 minutes on day 1 in weeks 1, 7, 13, 19, and 25; vincristine IV on day 1 in weeks 1-10, 13, 16, 19, 22, and 25; and doxorubicin hydrochloride IV over 15 minutes on day 1 in weeks 4,10, 16, and 22. Patients whose primary tumors were initially resected undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 291 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of High Risk Renal Tumors: A Groupwide Phase II Study
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Surgery Patients with completely resectable stage I-IV RCC undergo surgical resection. Patients with incompletely resectable stage III-IV RCC undergo treatment as per physician's choice.	Procedure: Conventional Surgery; Patients undergo resection; Other Names: surgery, conventional
Experimental: Treatment (UH-1) Patients receive combination chemotherapy comprising vincristine, doxorubicin hydrochloride, cyclophosphamide, etoposide, and carboplatin. Patients whose primary tumors were initially resected undergo radiotherapy once daily 5 days a week for 4-5½ weeks beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13. Patients with unresectable clear cell sarcoma of the kidney (CCSK) receive no further study therapy.	Drug: Doxorubicin Hydrochloride; Given IV; Procedure: Conventional Surgery; Patients undergo resection; Other Names: surgery, conventional ; Drug: Cyclophosphamide; Given IV; Drug: Etoposide; Given IV; Other Names: Lastet ; Drug: Carboplatin; Given IV; Drug: Vincristine Sulfate; Given IV; Other Names: Kyocristine Oncovin VCR Vincasar ; Radiation: Radiation Therapy; Undergo radiotherapy; Other Names: Cancer Radiotherapy Irradiate Irradiated Irradiation RT ; Other: Laboratory Biomarker Analysis; Correlative studies
Experimental: Treatment (window/UH-1) Patients receive vincristine IV on days 1 and 8 and irinotecan hydrochloride IV over 30 minutes on days 1-5 and 8-12 (course 1). Patients with progressive disease (PD) are treated with regimen UH-1. Patients with stable disease (SD), partial response (PR), or complete response (CR) receive another course of irinotecan hydrochloride/vincristine window therapy beginning on day 22. After the second course, patients with SD or PD are treated with regimen UH-1 and patients with PR or CR are treated with regimen UH-2.	Drug: Doxorubicin Hydrochloride; Given IV; Drug: Irinotecan Hydrochloride; Given IV; Procedure: Conventional Surgery; Patients undergo resection; Other Names: surgery, conventional ; Drug: Cyclophosphamide; Given IV; Drug: Etoposide; Given IV; Other Names: Lastet ; Drug: Carboplatin; Given IV; Drug: Vincristine Sulfate; Given IV; Other Names: Kyocristine Oncovin VCR Vincasar ; Radiation: Radiation Therapy; Undergo radiotherapy; Other Names: Cancer Radiotherapy Irradiate Irradiated Irradiation RT ; Other: Laboratory Biomarker Analysis; Correlative studies
Experimental: Treatment (UH-2) Patients receive combination chemotherapy comprising vincristine, doxorubicin hydrochloride, cyclophosphamide, etoposide, carboplatin, and irinotecan hydrochloride. Patients whose primary tumors were initially resected undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 7. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 7.	Drug: Doxorubicin Hydrochloride; Given IV; Drug: Irinotecan Hydrochloride; Given IV; Procedure: Conventional Surgery; Patients undergo resection; Other Names: surgery, conventional ; Drug: Etoposide; Given IV; Other Names: Lastet ; Drug: Carboplatin; Given IV; Drug: Vincristine Sulfate; Given IV; Other Names: Kyocristine Oncovin VCR Vincasar ; Radiation: Radiation Therapy; Undergo radiotherapy; Other Names: Cancer Radiotherapy Irradiate Irradiated Irradiation RT ; Other: Laboratory Biomarker Analysis; Correlative studies
Experimental: Treatment (regimen I) Patients receive vincristine, doxorubicin hydrochloride, cyclophosphamide, and etoposide. Patients whose primary tumors were initially resected (except those with stage I CCSK) undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13.	Drug: Doxorubicin Hydrochloride; Given IV; Procedure: Conventional Surgery; Patients undergo resection; Other Names: surgery, conventional ; Drug: Cyclophosphamide; Given IV; Drug: Etoposide; Given IV; Other Names: Lastet ; Drug: Vincristine Sulfate; Given IV; Other Names: Kyocristine Oncovin VCR Vincasar ; Radiation: Radiation Therapy; Undergo radiotherapy; Other Names: Cancer Radiotherapy Irradiate Irradiated Irradiation RT ; Other: Laboratory Biomarker Analysis; Correlative studies
Experimental: Treatment (regimen DD-4A) Patients receive dactinomycin, vincristine, and doxorubicin hydrochloride. Patients whose primary tumors were initially resected undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 1. Patients with delayed primary tumor resection undergo radiotherapy as in regimen UH-1 beginning on day 1 in week 13. If the primary tumor was not previously resected, patients undergo resection, if feasible, in week 13.	Drug: Doxorubicin Hydrochloride; Given IV; Procedure: Conventional Surgery; Patients undergo resection; Other Names: surgery, conventional ; Biological: Dactinomycin; Given IV; Other Names: Lyovac Cosmegen ; Drug: Vincristine Sulfate; Given IV; Other Names: Kyocristine Oncovin VCR Vincasar ; Radiation: Radiation Therapy; Undergo radiotherapy; Other Names: Cancer Radiotherapy Irradiate Irradiated Irradiation RT ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Event-Free Survival of Patients With Diffuse Anaplastic Wilms' Tumor (DAWT) [4 years]

   Compare the outcome of patients treated with alternating CyCE/VDCy chemotherapy (with or without vincristine/irinotecan cycles) to a fixed outcome based on that seen for similar patients treated with NWTS-5 (NCT00002610).

2. Long-term Survival of Patients With Stage I-IV Malignant Rhabdoid Tumors [4 years]

   The outcome of these patients will be compared with a fixed outcome based on that seen for similar patients treated with NWTS-5 regimen (NCT00002610).

3. Response Rate [Up to 2 months]

   Criteria for response assessed by three-dimensional measurement: Complete Response (CR), Disappearance of all index lesions and non-index lesions. No new lesions; Partial Response (PR), At least a 65% decrease in the sum of the volumes of the index lesions. No new lesions; Response rate (RR) = CR+PR of patients who received window therapy.

4. Event Free Survival Probability [4 years]

   Event-free survival will be informally compared to that seem for similar patients treated on NWTS-5 (NCT00002610).

5. Toxicity Rate [Up to 4 years]

   Percentage of participants with Grade 4 cardiac toxicities, Grade 4 Sinusoidal Obstruction Syndrome (SOS), and treatment-related deaths determined using CTCAE v4.

Secondary Outcome Measures

1. Number of Patients With INI1 Mutations in Renal and Extrarenal Malignant Rhabdoid Tumor by Fluorescent in Situ Hybridization [At baseline]

2. Frequency of TP53 Mutations [At baseline]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 29 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Newly diagnosed disease of 1 of the following histologic types:

• Focal anaplastic Wilms' tumor

• Diffuse anaplastic Wilms' tumor

• Clear cell sarcoma of the kidney

• Malignant rhabdoid tumor (renal or extrarenal)

• Renal cell carcinoma

• Clear cell

• Papillary

• Renal medullary

• Oncocytoid

• Sarcomatoid

• Chromophobe

• Translocation

• Collecting duct

• Carcinoma associated with neuroblastoma

• Renal cell carcinoma unclassified

• Specimens/materials must be submitted for central review by Day 7

• Patients must begin protocol therapy on AREN0321 by Day 14 after surgery or biopsy (surgery/biopsy is Day 0), unless medically contraindicated

• Karnofsky performance status (PS) must be >= 50 for patients > 16 years if age and Lansky PS must be >= 50 for patients =< 16 years of age

• Patients must not have received systemic chemotherapy or radiation therapy prior to treatment on this study UNLESS they were enrolled on the AREN0532 or AREN0533 studies and received prenephrectomy chemotherapy for what was originally presumed to be favorable histology Wilms tumor; additionally, patients with pediatric RCC who previously received chemotherapy for another type of malignancy (not the RCC) or non-malignant condition may enroll on the study

• Total bilirubin =< 1.5 times upper limit of normal (ULN) for age

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST] or serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ ALT]) < 2.5 times ULN for age

• Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by radionuclide angiogram

• Female patients of childbearing age must have a negative pregnancy test

• Female patients who are lactating must agree to stop breast-feeding

• Sexually active patients of childbearing potential must agree to use effective contraception

• All patients and/or their parents or legal guardians must sign a written informed consent

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
3	University of South Alabama	Mobile	Alabama	United States	36604
4	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
5	University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724
6	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202-3591
7	Southern California Permanente Medical Group	Downey	California	United States	90242
8	Loma Linda University Medical Center	Loma Linda	California	United States	92354
9	Miller Children's Hospital	Long Beach	California	United States	90806
10	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
11	Children's Hospital Central California	Madera	California	United States	93636-8762
12	Children's Hospital and Research Center at Oakland	Oakland	California	United States	94609-1809
13	Kaiser Permanente-Oakland	Oakland	California	United States	94611
14	Childrens Hospital of Orange County	Orange	California	United States	92868
15	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
16	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
17	University of California San Francisco Medical Center-Parnassus	San Francisco	California	United States	94143
18	Children's Hospital Colorado	Aurora	Colorado	United States	80045
19	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado	United States	80218
20	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
21	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
22	Children's National Medical Center	Washington, D.C.	District of Columbia	United States	20010
23	Lombardi Comprehensive Cancer Center at Georgetown University	Washington, D.C.	District of Columbia	United States	20057
24	Broward Health Medical Center	Fort Lauderdale	Florida	United States	33316
25	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
26	Memorial Healthcare System - Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
27	Nemours Children's Clinic-Jacksonville South	Jacksonville	Florida	United States	32207
28	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
29	Miami Children's Hospital	Miami	Florida	United States	33155
30	Baptist Hospital of Miami	Miami	Florida	United States	33176
31	Florida Hospital Orlando	Orlando	Florida	United States	32803
32	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
33	Nemours Children's Clinic - Pensacola	Pensacola	Florida	United States	32504
34	All Children's Hospital	Saint Petersburg	Florida	United States	33701
35	Saint Joseph Children's Hospital of Tampa	Tampa	Florida	United States	33607
36	Saint Mary's Hospital	West Palm Beach	Florida	United States	33407
37	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
38	Memorial University Medical Center	Savannah	Georgia	United States	31404
39	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
40	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
41	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
42	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60611
43	University of Illinois	Chicago	Illinois	United States	60612
44	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
45	Loyola University Medical Center	Maywood	Illinois	United States	60153
46	Advocate Children's Hospital-Oak Lawn	Oak Lawn	Illinois	United States	60453
47	Advocate Lutheran General Hospital.	Park Ridge	Illinois	United States	60068
48	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61602
49	Southern Illinois University	Springfield	Illinois	United States	62702
50	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
51	Saint Vincent Hospital and Health Services	Indianapolis	Indiana	United States	46260
52	Blank Children's Hospital	Des Moines	Iowa	United States	50309
53	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
54	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
55	Kosair Children's Hospital	Louisville	Kentucky	United States	40202
56	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
57	Children's Hospital New Orleans	New Orleans	Louisiana	United States	70118
58	Eastern Maine Medical Center	Bangor	Maine	United States	04401
59	Maine Children's Cancer Program	Scarborough	Maine	United States	04074
60	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
61	Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21287
62	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
63	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
64	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
65	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
66	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
67	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
68	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
69	Michigan State University Clinical Center	East Lansing	Michigan	United States	48824-7016
70	Hurley Medical Center	Flint	Michigan	United States	48502
71	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
72	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
73	Kalamazoo Center for Medical Studies	Kalamazoo	Michigan	United States	49008
74	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
75	Mayo Clinic	Rochester	Minnesota	United States	55905
76	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
77	The Childrens Mercy Hospital	Kansas City	Missouri	United States	64108
78	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
79	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
80	Saint John's Mercy Medical Center	Saint Louis	Missouri	United States	63141
81	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska	United States	68114
82	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
83	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
84	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
85	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
86	Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
87	UMDNJ - Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
88	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
89	Saint Joseph's Regional Medical Center	Paterson	New Jersey	United States	07503
90	Overlook Hospital	Summit	New Jersey	United States	07902
91	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87106
92	University of New Mexico	Albuquerque	New Mexico	United States	87106
93	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
94	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York	United States	11040
95	New York University Langone Medical Center	New York	New York	United States	10016
96	Columbia University Medical Center	New York	New York	United States	10032
97	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
98	Weill Medical College of Cornell University	New York	New York	United States	10065
99	University of Rochester	Rochester	New York	United States	14642
100	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
101	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
102	Mission Hospital-Memorial Campus	Asheville	North Carolina	United States	28801
103	University of North Carolina	Chapel Hill	North Carolina	United States	27599
104	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
105	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
106	Duke University Medical Center	Durham	North Carolina	United States	27710
107	East Carolina University	Greenville	North Carolina	United States	27858
108	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
109	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
110	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
111	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
112	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
113	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
114	Dayton Children's Hospital	Dayton	Ohio	United States	45404
115	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
116	Mercy Children's Hospital	Toledo	Ohio	United States	43608
117	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
118	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma	United States	74136
119	Legacy Emanuel Children's Hospital	Portland	Oregon	United States	97227
120	Legacy Emanuel Hospital and Health Center	Portland	Oregon	United States	97227
121	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
122	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
123	Penn State Hershey Children's Hospital	Hershey	Pennsylvania	United States	17033
124	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
125	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134
126	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
127	Rhode Island Hospital	Providence	Rhode Island	United States	02903
128	Palmetto Health Richland	Columbia	South Carolina	United States	29203
129	BI-LO Charities Children's Cancer Center	Greenville	South Carolina	United States	29605
130	Greenville Cancer Treatment Center	Greenville	South Carolina	United States	29605
131	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
132	T C Thompson Children's Hospital	Chattanooga	Tennessee	United States	37403
133	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
134	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
135	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
136	Texas Tech University Health Science Center-Amarillo	Amarillo	Texas	United States	79106
137	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
138	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
139	Medical City Dallas Hospital	Dallas	Texas	United States	75230
140	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
141	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
142	Baylor College of Medicine	Houston	Texas	United States	77030
143	Covenant Children's Hospital	Lubbock	Texas	United States	79410
144	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
145	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
146	Scott and White Memorial Hospital	Temple	Texas	United States	76508
147	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
148	University of Vermont College of Medicine	Burlington	Vermont	United States	05405
149	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
150	Childrens Hospital-King's Daughters	Norfolk	Virginia	United States	23507
151	Naval Medical Center - Portsmouth	Portsmouth	Virginia	United States	23708-2197
152	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
153	Carilion Clinic Children's Hospital	Roanoke	Virginia	United States	24014
154	Seattle Children's Hospital	Seattle	Washington	United States	98105
155	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
156	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington	United States	98405
157	Madigan Army Medical Center	Tacoma	Washington	United States	98431
158	West Virginia University Charleston	Charleston	West Virginia	United States	25304
159	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
160	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
161	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
162	John Hunter Children's Hospital	Hunter Regional Mail Centre	New South Wales	Australia	2310
163	Sydney Children's Hospital	Randwick	New South Wales	Australia	2031
164	The Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
165	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
166	Royal Children's Hospital-Brisbane	Herston	Queensland	Australia	4029
167	Women's and Children's Hospital-Adelaide	North Adelaide	South Australia	Australia	5006
168	Royal Children's Hospital	Parkville	Victoria	Australia	3052
169	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6008
170	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
171	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
172	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
173	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
174	Janeway Child Health Centre	Saint John's	Newfoundland and Labrador	Canada	A1B 3V6
175	IWK Health Centre	Halifax	Nova Scotia	Canada	B3J 3G9
176	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
177	Chedoke-McMaster Hospitals	Hamilton	Ontario	Canada	L8S 4L8
178	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	K7L 5P9
179	Children's Hospital	London	Ontario	Canada	N6A 5W9
180	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
181	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
182	The Montreal Children's Hospital of the MUHC	Montreal	Quebec	Canada	H3H 1P3
183	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
184	Centre Hospitalier Universitaire de Quebec	Ste-Foy	Quebec	Canada	G1V 4G2
185	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4
186	Starship Children's Hospital	Grafton	Auckland	New Zealand	1145
187	San Jorge Children's Hospital	San Juan		Puerto Rico	00912

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Jeffrey Dome, MD, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00335556
• Other Study ID Numbers: AREN0321; NCI-2009-00414; COG-AREN0321; CDR0000472893; AREN0321; AREN0321; U10CA098543
• First Posted: Jun 12, 2006
• Last Update Posted: Jul 21, 2017
• Last Verified: Apr 1, 2016

• Additional relevant MeSH terms: Carcinoma; Neoplasms; Carcinoma, Renal Cell; Wilms Tumor; Rhabdoid Tumor; Sarcoma, Clear Cell; Kidney Neoplasms; Dactinomycin; Cyclophosphamide; Carboplatin; Doxorubicin; Liposomal doxorubicin; Irinotecan; Etoposide; Vincristine

Study Results

Participant Flow

Arm/Group Title	Surgery	UH-1	Window/UH-1	UH-2	Regimen I	Regimen DD-4A
Arm/Group Description	Surgery Only	Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 30 weeks; XRT.	Window therapy of vincristine/irinotecan;Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 30 weeks; XRT.	Window therapy of vincristine/irinotecan;Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 36 weeks; XRT.	Vincristine/doxorubicin/cyclophosphamide; cyclophosphamide/etoposide x25 weeks; XRT.	Vincristine/dactinomycin/doxorubicin x25 weeks; XRT.
Period Title: Overall Study
STARTED	68	98	7	10	78	30
COMPLETED	66	64	2	5	77	29
NOT COMPLETED	2	34	5	5	1	1

Baseline Characteristics

Arm/Group Title	Surgery	UH-1	Window/UH-1	UH-2	Regimen I	Regimen DD-4A	Total
Arm/Group Description	Surgery Only	Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 30 weeks; XRT.	Window therapy of vincristine/irinotecan;Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 30 weeks; XRT.	Window therapy of vincristine/irinotecan;Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 36 weeks; XRT.	Vincristine/doxorubicin/cyclophosphamide; cyclophosphamide/etoposide x25 weeks; XRT.	Vincristine/dactinomycin/doxorubicin x25 weeks; XRT.	Total of all reporting groups
Overall Participants	68	98	7	10	78	30	291
Age (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	148.53 (51.74)	52.39 (40.09)	68.95 (97.64)	54.04 (19.71)	34.10 (31.10)	54.29 (32.72)	70.60 (60.50)
Sex: Female, Male (Count of Participants)
Female	28 41.2%	55 56.1%	5 71.4%	7 70%	31 39.7%	11 36.7%	137 47.1%
Male	40 58.8%	43 43.9%	2 28.6%	3 30%	47 60.3%	19 63.3%	154 52.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 7.4%	8 8.2%	0 0%	2 20%	15 19.2%	4 13.3%	34 11.7%
Not Hispanic or Latino	63 92.6%	88 89.8%	6 85.7%	8 80%	63 80.8%	25 83.3%	253 86.9%
Unknown or Not Reported	0 0%	2 2%	1 14.3%	0 0%	0 0%	1 3.3%	4 1.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 1.5%	1 1%	0 0%	0 0%	3 3.8%	0 0%	5 1.7%
Native Hawaiian or Other Pacific Islander	1 1.5%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.3%
Black or African American	22 32.4%	17 17.3%	1 14.3%	2 20%	13 16.7%	5 16.7%	60 20.6%
White	40 58.8%	72 73.5%	5 71.4%	8 80%	55 70.5%	22 73.3%	202 69.4%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	4 5.9%	8 8.2%	1 14.3%	0 0%	7 9%	3 10%	23 7.9%

Outcome Measures

1. Primary Outcome

Title	Event-Free Survival of Patients With Diffuse Anaplastic Wilms' Tumor (DAWT)
Description	Compare the outcome of patients treated with alternating CyCE/VDCy chemotherapy (with or without vincristine/irinotecan cycles) to a fixed outcome based on that seen for similar patients treated with NWTS-5 (NCT00002610).
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Eligible patients with Stage II-IV DAWT.

Arm/Group Title	UH-1	Window/UH-1	UH-2
Arm/Group Description	Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 30 weeks; XRT.	Window therapy of vincristine/irinotecan;Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 30 weeks; XRT.	Window therapy of vincristine/irinotecan;Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 36 weeks; XRT.
Measure Participants	52	4	10
Number (95% Confidence Interval) [Percentage of 4-year OS]	76.1	25.0	87.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UH-1, Window/UH-1, UH-2
	Comments	The event-free survival distributions of patients with Stage II-IV diffuse anaplastic Wilms' tumor on AREN0321 and NWTS-5 (NCT00002610) were compared using the log-rank test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.0199
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Log Rank Test Statistic
	Estimated Value	5.4190
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Long-term Survival of Patients With Stage I-IV Malignant Rhabdoid Tumors
Description	The outcome of these patients will be compared with a fixed outcome based on that seen for similar patients treated with NWTS-5 regimen (NCT00002610).
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Eligible patients with Stage I-IV rhabdoid tumor.

Arm/Group Title	UH-1
Arm/Group Description	Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphamide; x 30 weeks; XRT.
Measure Participants	36
Number (95% Confidence Interval) [Percentage of 4-year OS]	38.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UH-1
	Comments	The overall survival distributions of patients with Stage I-IV malignant rhabdoid tumors on AREN0321 and National Wilms Tumor Study-5 -- Treatment of Relapsed Patients, A National Wilms Tumor Study Group Phase III Study (NCT00002610) were compared using the log-rank test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.3478
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Log Rank Test Statistic
	Estimated Value	.8814
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Response Rate
Description	Criteria for response assessed by three-dimensional measurement: Complete Response (CR), Disappearance of all index lesions and non-index lesions. No new lesions; Partial Response (PR), At least a 65% decrease in the sum of the volumes of the index lesions. No new lesions; Response rate (RR) = CR+PR of patients who received window therapy.
Time Frame	Up to 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Combined Window/UH-1 and UH-2
Arm/Group Description	Combine window/UH-1 and UH-2 for response rate monitoring for window therapy.
Measure Participants	17
Number (95% Confidence Interval) [Percentage of participants]	71 104.4%

4. Primary Outcome

Title	Event Free Survival Probability
Description	Event-free survival will be informally compared to that seem for similar patients treated on NWTS-5 (NCT00002610).
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Eligible patients with Stage I focal and diffuse anaplastic Wilms tumor.

Arm/Group Title	Regimen DD-4A
Arm/Group Description	Vincristine/dactinomycin/doxorubicin x25 weeks; XRT.
Measure Participants	18
Number (95% Confidence Interval) [Percent Probability 4 Year EFS]	100.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UH-1
	Comments	The event-free survival distributions of patients with Stage I focal and diffuse anaplastic Wilms tumors on AREN0321 and National Wilms Tumor Study-5 -- Treatment of Relapsed Patients, A National Wilms Tumor Study Group Phase III Study (NCT00002610) were compared using the log-rank test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.0570
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Log Rank Test Statistic
	Estimated Value	3.6216
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Toxicity Rate
Description	Percentage of participants with Grade 4 cardiac toxicities, Grade 4 Sinusoidal Obstruction Syndrome (SOS), and treatment-related deaths determined using CTCAE v4.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Eligible patients treated after Amendment 3A for arms UH-1, UH-2, and Window/UH-1.

Arm/Group Title	Combined UH-2, UH-1, Window/UH-1
Arm/Group Description	Combined UH-1, UH-2, and Window/UH-1 for revised-UH toxicity monitoring
Measure Participants	61
Cardiac toxicities	4.9
Treatment-related deaths	4.9
Sinusoidal Obstruction Syndrome	0

6. Secondary Outcome

Title	Number of Patients With INI1 Mutations in Renal and Extrarenal Malignant Rhabdoid Tumor by Fluorescent in Situ Hybridization
Time Frame	At baseline

Outcome Measure Data

Analysis Population Description

Eligible patients with reported INI1 mutation data.

Arm/Group Title	UH-1	Window/UH-1
Arm/Group Description	Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 30 weeks; XRT.	Window therapy of vincristine/irinotecan;Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 30 weeks; XRT.
Measure Participants	26	1
Number [Count participants]	23 33.8%	1 1%

7. Secondary Outcome

Title	Frequency of TP53 Mutations
Time Frame	At baseline

Outcome Measure Data

Analysis Population Description

The analysis was supplanted by an analysis done as part of the TARGET initiative on NWTS-5 sample as a result no TP53 data was collected on AREN0321.

Arm/Group Title	UH-1	Window/UH-1	UH-2	Regimen DD-4A
Arm/Group Description	Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide;x 30 weeks; XRT.	Window therapy of vincristine/irinotecan;Cyclophosphamide/carboplatin/etoposide;vincristine/doxorubicin/cyclophosphomide; x 30 weeks; XRT.	Window therapy of vincristine/irinotecan;Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 36 weeks; XRT	Vincristine/dactinomycin/doxorubicin x25 weeks; XRT
Measure Participants	0	0	0	0

Adverse Events

Arm/Group Title	Surgery		UH-1		Window/UH-1		UH-2		Regimen I		Regimen DD-4A
Arm/Group Description	Surgery Only		Cyclophosphamide/carboplatin/etoposide;vincristine/doxorubicin/cyclophosphomide; x 30 weeks; XRT		Window therapy of vincristine/irinotecan; Cyclophosphamide/carboplatin/etoposide;vincristine/doxorubicin/cyclophosphomide; x 30 weeks; XRT"		Window therapy of vincristine/irinotecan;Cyclophosphamide/carboplatin/etoposide; vincristine/doxorubicin/cyclophosphomide; x 36 weeks; XRT		Vincristine/doxorubicin/cyclophosphamide; cyclophosphamide/etoposide x25 weeks; XRT		Vincristine/dactinomycin/doxorubicin x25 weeks; XRT"
All Cause Mortality
	Surgery		UH-1		Window/UH-1		UH-2		Regimen I		Regimen DD-4A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Surgery		UH-1		Window/UH-1		UH-2		Regimen I		Regimen DD-4A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/66 (3%)		19/98 (19.4%)		3/7 (42.9%)		0/10 (0%)		3/78 (3.8%)		1/30 (3.3%)
Cardiac disorders
20000-Cardiac arrest	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
20100-Cardiac disorders - Other specify	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
39000-Heart failure	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
51700-Left ventricular systolic dysfunction	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Gastrointestinal disorders
10300-Abdominal pain	0/66 (0%)	0	0/98 (0%)	0	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
14900-Ascites	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
44200-Ileal obstruction	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
87900-Vomiting	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
General disorders
24600-Death NOS	0/66 (0%)	0	5/98 (5.1%)	5	2/7 (28.6%)	2	0/10 (0%)	0	2/78 (2.6%)	2	1/30 (3.3%)	1
37200-General disorders and administration site conditions	1/66 (1.5%)	1	0/98 (0%)	0	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
55700-Multi-organ failure	0/66 (0%)	0	0/98 (0%)	0	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
60600-Pain	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
78300-Sudden death NOS	1/66 (1.5%)	1	0/98 (0%)	0	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Infections and infestations
44800-Infections and infestations - Other specify	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	0/10 (0%)	0	1/78 (1.3%)	3	0/30 (0%)	0
53100-Lung infection	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	0/10 (0%)	0	1/78 (1.3%)	1	0/30 (0%)	0
73700-Sepsis	0/66 (0%)	0	1/98 (1%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Investigations
11600-Alanine aminotransferase increased	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
15000-Aspartate aminotransferase increased	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
17400-Blood bilirubin increased	0/66 (0%)	0	2/98 (2%)	2	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
24100-Creatinine increased	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
34000-Fibrinogen decreased	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
52600-Lipase increased	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
65800-Platelet count decreased	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
88200-Weight gain	0/66 (0%)	0	0/98 (0%)	0	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Metabolism and nutrition disorders
24700-Dehydration	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
43100-Hypokalemia	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
43300-Hyponatremia	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
43500-Hypophosphatemia	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
58000-Neoplasms benign malignant and unspecified (incl cy	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
81200-Treatment related secondary malignancy	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Nervous system disorders
58100-Nervous system disorders - Other specify	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Renal and urinary disorders
11100-Acute kidney injury	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Respiratory, thoracic and mediastinal disorders
11300-Adult respiratory distress syndrome	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
19200-Bronchopulmonary hemorrhage	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
43900-Hypoxia	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
65900-Pleural effusion	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
66000-Pleural hemorrhage	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
66300-Pneumonitis	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
66400-Pneumothorax	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
68700-Pulmonary edema	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
69000-Pulmonary hypertension	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
71500-Respiratory failure	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Vascular disorders
43600-Hypotension	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Other (Not Including Serious) Adverse Events
	Surgery		UH-1		Window/UH-1		UH-2		Regimen I		Regimen DD-4A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/66 (0%)		81/98 (82.7%)		5/7 (71.4%)		9/10 (90%)		7/78 (9%)		1/30 (3.3%)
Blood and lymphatic system disorders
13200-Anemia	0/66 (0%)	0	4/98 (4.1%)	6	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
17200-Blood and lymphatic system disorders - Other specif	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
25800-Disseminated intravascular coagulation	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
33300-Febrile neutropenia	0/66 (0%)	0	56/98 (57.1%)	86	3/7 (42.9%)	5	8/10 (80%)	12	4/78 (5.1%)	6	0/30 (0%)	0
Cardiac disorders
20000-Cardiac arrest	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
51700-Left ventricular systolic dysfunction	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
56900-Myocarditis	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
63100-Pericardial effusion	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
72700-Right ventricular dysfunction	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
Ear and labyrinth disorders
38900-Hearing impaired	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	1/30 (3.3%)	1
Gastrointestinal disorders
10100-Abdominal distension	0/66 (0%)	0	0/98 (0%)	0	2/7 (28.6%)	2	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
10300-Abdominal pain	0/66 (0%)	0	6/98 (6.1%)	6	1/7 (14.3%)	1	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
14900-Ascites	0/66 (0%)	0	0/98 (0%)	0	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
22100-Colitis	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
22200-Colonic fistula	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
22300-Colonic hemorrhage	0/66 (0%)	0	0/98 (0%)	0	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
25700-Diarrhea	0/66 (0%)	0	10/98 (10.2%)	11	1/7 (14.3%)	1	3/10 (30%)	3	0/78 (0%)	0	0/30 (0%)	0
27600-Dysphagia	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
29400-Enterocolitis	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
31200-Esophagitis	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
36400-Gastritis	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
36700-Gastrointestinal disorders - Other specify	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
46300-Intra-abdominal hemorrhage	0/66 (0%)	0	0/98 (0%)	0	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
53900-Malabsorption	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
55600-Mucositis oral	0/66 (0%)	0	9/98 (9.2%)	9	1/7 (14.3%)	1	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
57600-Nausea	0/66 (0%)	0	5/98 (5.1%)	6	1/7 (14.3%)	1	0/10 (0%)	0	1/78 (1.3%)	1	0/30 (0%)	0
59600-Oral hemorrhage	0/66 (0%)	0	0/98 (0%)	0	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
59700-Oral pain	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
61800-Pancreatitis	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
75700-Small intestinal obstruction	0/66 (0%)	0	1/98 (1%)	1	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
81900-Typhlitis	0/66 (0%)	0	2/98 (2%)	2	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
87900-Vomiting	0/66 (0%)	0	9/98 (9.2%)	9	2/7 (28.6%)	2	1/10 (10%)	1	1/78 (1.3%)	1	0/30 (0%)	0
General disorders
28200-Edema face	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
33900-Fever	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
55700-Multi-organ failure	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
60600-Pain	0/66 (0%)	0	1/98 (1%)	1	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Hepatobiliary disorders
40000-Hepatic failure	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
40600-Hepatobiliary disorders - Other specify	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
66500-Portal hypertension	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Immune system disorders
13100-Anaphylaxis	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Infections and infestations
10200-Abdominal infection	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
20500-Catheter related infection	0/66 (0%)	0	7/98 (7.1%)	7	1/7 (14.3%)	1	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
29500-Enterocolitis infectious	0/66 (0%)	0	4/98 (4.1%)	5	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
44800-Infections and infestations - Other specify	0/66 (0%)	0	44/98 (44.9%)	77	4/7 (57.1%)	4	4/10 (40%)	13	1/78 (1.3%)	3	0/30 (0%)	0
53100-Lung infection	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
60100-Otitis media	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
62500-Pelvic infection	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
64200-Peritoneal infection	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
65200-Pharyngitis	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
73700-Sepsis	0/66 (0%)	0	2/98 (2%)	2	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
74600-Sinusitis	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
75200-Skin infection	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
76000-Small intestine infection	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
76400-Soft tissue infection	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
82300-Upper respiratory infection	0/66 (0%)	0	3/98 (3.1%)	3	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
83100-Urinary tract infection	0/66 (0%)	0	4/98 (4.1%)	5	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
88900-Wound infection	0/66 (0%)	0	1/98 (1%)	1	1/7 (14.3%)	1	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
Injury, poisoning and procedural complications
86400-Vascular access complication	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Investigations
11600-Alanine aminotransferase increased	0/66 (0%)	0	9/98 (9.2%)	10	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
15000-Aspartate aminotransferase increased	0/66 (0%)	0	8/98 (8.2%)	8	1/7 (14.3%)	1	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
17400-Blood bilirubin increased	0/66 (0%)	0	2/98 (2%)	2	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
24100-Creatinine increased	0/66 (0%)	0	3/98 (3.1%)	3	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
37500-GGT increased	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
48400-Investigations - Other specify	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
52600-Lipase increased	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
53700-Lymphocyte count decreased	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
58300-Neutrophil count decreased	0/66 (0%)	0	6/98 (6.1%)	8	0/7 (0%)	0	1/10 (10%)	1	2/78 (2.6%)	3	0/30 (0%)	0
65800-Platelet count decreased	0/66 (0%)	0	5/98 (5.1%)	7	0/7 (0%)	0	1/10 (10%)	1	1/78 (1.3%)	1	0/30 (0%)	0
73900-Serum amylase increased	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
83600-Urine output decreased	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
88300-Weight loss	0/66 (0%)	0	1/98 (1%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
88500-White blood cell decreased	0/66 (0%)	0	4/98 (4.1%)	5	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Metabolism and nutrition disorders
10700-Acidosis	0/66 (0%)	0	3/98 (3.1%)	3	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
13500-Anorexia	0/66 (0%)	0	20/98 (20.4%)	22	2/7 (28.6%)	3	2/10 (20%)	2	3/78 (3.8%)	4	0/30 (0%)	0
24700-Dehydration	0/66 (0%)	0	9/98 (9.2%)	10	0/7 (0%)	0	2/10 (20%)	2	0/78 (0%)	0	0/30 (0%)	0
41300-Hypercalcemia	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
41400-Hyperglycemia	0/66 (0%)	0	4/98 (4.1%)	5	1/7 (14.3%)	1	2/10 (20%)	5	0/78 (0%)	0	0/30 (0%)	0
41600-Hyperkalemia	0/66 (0%)	0	4/98 (4.1%)	4	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
41800-Hypernatremia	0/66 (0%)	0	0/98 (0%)	0	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
42600-Hypoalbuminemia	0/66 (0%)	0	4/98 (4.1%)	4	2/7 (28.6%)	3	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
42700-Hypocalcemia	0/66 (0%)	0	4/98 (4.1%)	4	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
42900-Hypoglycemia	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	1/10 (10%)	2	0/78 (0%)	0	0/30 (0%)	0
43100-Hypokalemia	0/66 (0%)	0	14/98 (14.3%)	19	3/7 (42.9%)	4	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
43200-Hypomagnesemia	0/66 (0%)	0	1/98 (1%)	1	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
43300-Hyponatremia	0/66 (0%)	0	8/98 (8.2%)	8	1/7 (14.3%)	1	2/10 (20%)	2	0/78 (0%)	0	0/30 (0%)	0
43500-Hypophosphatemia	0/66 (0%)	0	5/98 (5.1%)	7	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
Musculoskeletal and connective tissue disorders
60700-Pain in extremity	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
81800-Tumor pain	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Nervous system disorders
32400-Facial nerve disorder	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
41200-Hydrocephalus	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
58100-Nervous system disorders - Other specify	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	0/10 (0%)	0	1/78 (1.3%)	1	0/30 (0%)	0
63900-Peripheral motor neuropathy	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	1/78 (1.3%)	1	0/30 (0%)	0
64100-Peripheral sensory neuropathy	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Psychiatric disorders
11400-Agitation	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
Renal and urinary disorders
11100-Acute kidney injury	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
24300-Cystitis noninfective	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
39300-Hematuria	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
68300-Proteinuria	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Respiratory, thoracic and mediastinal disorders
11300-Adult respiratory distress syndrome	0/66 (0%)	0	1/98 (1%)	1	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
14100-Apnea	0/66 (0%)	0	0/98 (0%)	0	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
15400-Atelectasis	0/66 (0%)	0	1/98 (1%)	1	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
27800-Dyspnea	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	2/10 (20%)	2	0/78 (0%)	0	0/30 (0%)	0
29700-Epistaxis	0/66 (0%)	0	1/98 (1%)	1	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
43900-Hypoxia	0/66 (0%)	0	6/98 (6.1%)	6	2/7 (28.6%)	3	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
65300-Pharyngolaryngeal pain	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
65900-Pleural effusion	0/66 (0%)	0	4/98 (4.1%)	4	0/7 (0%)	0	2/10 (20%)	3	0/78 (0%)	0	0/30 (0%)	0
66300-Pneumonitis	0/66 (0%)	0	2/98 (2%)	2	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
68700-Pulmonary edema	0/66 (0%)	0	0/98 (0%)	0	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0
69000-Pulmonary hypertension	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Skin and subcutaneous tissue disorders
69200-Purpura	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
74700-Skin and subcutaneous tissue disorders - Other spec	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
Vascular disorders
39100-Hematoma	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
42100-Hypertension	0/66 (0%)	0	8/98 (8.2%)	9	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
43600-Hypotension	0/66 (0%)	0	8/98 (8.2%)	8	1/7 (14.3%)	1	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
53500-Lymphedema	0/66 (0%)	0	1/98 (1%)	1	0/7 (0%)	0	0/10 (0%)	0	0/78 (0%)	0	0/30 (0%)	0
79600-Thromboembolic event	0/66 (0%)	0	3/98 (3.1%)	4	0/7 (0%)	0	1/10 (10%)	1	0/78 (0%)	0	0/30 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Must obtain prior Sponsor approval.