Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00945009
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 249
• Locations: 169
• Arms: 3
• Anticipated Duration (Months): 172.5
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase III trial studies how well combination chemotherapy and surgery work in treating young patients with Wilms tumor. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.

Condition or Disease	Intervention/Treatment	Phase
Adult Kidney Wilms Tumor; Beckwith-Wiedemann Syndrome; Childhood Kidney Wilms Tumor; Diffuse Hyperplastic Perilobar Nephroblastomatosis; Hemihypertrophy; Rhabdoid Tumor of the Kidney; Stage I Kidney Wilms Tumor; Stage II Kidney Wilms Tumor; Stage III Kidney Wilms Tumor; Stage IV Kidney Wilms Tumor; Stage V Kidney Wilms Tumor	Biological: Dactinomycin; Drug: Doxorubicin Hydrochloride; Radiation: Radiation Therapy; Procedure: Therapeutic Conventional Surgery; Drug: Vincristine Sulfate	Phase 3

Detailed Description

OBJECTIVES:

1. To improve 4-year event-free survival (EFS) to 73% for young patients with bilateral Wilms tumor (BWT).

2. To prevent complete removal of at least one kidney in 50% of patients with BWT by using prenephrectomy 3-drug chemotherapy induction with vincristine (vincristine sulfate), dactinomycin, and doxorubicin (doxorubicin hydrochloride).

3. To evaluate the efficacy of chemotherapy in preserving renal units in children with diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) and preventing Wilms tumor development.

4. To facilitate partial nephrectomy in lieu of nephrectomy in 25% of children with unilateral tumors and aniridia, Beckwith-Wiedemann syndrome (BWS), hemihypertrophy or other overgrowth syndromes, by using prenephrectomy 2-drug chemotherapy induction with vincristine and dactinomycin.

5. To have 75% of patients with BWT undergo definitive surgical treatment by 12 weeks after initiation of chemotherapy.

OUTLINE: Patients are assigned to 1 of 3 arms.

ARM 1 (Bilateral Wilms Tumors): Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy.

ARM 2 (Unilateral High Risk tumors bilaterally predisposed): Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy.

ARM 3 (DHPLN): Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy.

VAD REGIMEN: Patients receive vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6) and dactinomycin IV and doxorubicin hydrochloride IV over 15-120 minutes on days 1 and 22 (weeks 1 and 4).

EE4A REGIMEN: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 22, 29, and 36 (weeks 1-6) and dactinomycin IV over 1-5 minutes on days 1 and 22 (weeks 1 and 4).

After completion of study treatment, patients are followed up periodically for 10 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 249 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment for Patients With Bilateral, Multicentric, or Bilaterally-Predisposed Unilateral Wilms Tumor
• Actual Study Start Date: Jul 13, 2009
• Actual Primary Completion Date: Dec 31, 2016
• Anticipated Study Completion Date: Nov 26, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 (Bilateral Wilms Tumors) Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy.	Biological: Dactinomycin; Given IV; Other Names: Actinomycin A IV Actinomycin C1 ACTINOMYCIN D Actinomycin I1 Actinomycin IV Actinomycin X 1 Actinomycin-[thr-val-pro-sar-meval] Cosmegen DACT Dactinomycine Lyovac Cosmegen Meractinomycin ; Drug: Doxorubicin Hydrochloride; Given IV; Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex ; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy Irradiate Irradiated irradiation Radiation Radiotherapeutics RADIOTHERAPY RT Therapy, Radiation ; Procedure: Therapeutic Conventional Surgery; Undergo surgical resection; Drug: Vincristine Sulfate; Given IV; Other Names: Kyocristine Leurocristine sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate
Experimental: Arm 2 (Unilateral High Risk tumors bilaterally predisposed) Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy.	Biological: Dactinomycin; Given IV; Other Names: Actinomycin A IV Actinomycin C1 ACTINOMYCIN D Actinomycin I1 Actinomycin IV Actinomycin X 1 Actinomycin-[thr-val-pro-sar-meval] Cosmegen DACT Dactinomycine Lyovac Cosmegen Meractinomycin ; Drug: Doxorubicin Hydrochloride; Given IV; Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex ; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy Irradiate Irradiated irradiation Radiation Radiotherapeutics RADIOTHERAPY RT Therapy, Radiation ; Procedure: Therapeutic Conventional Surgery; Undergo surgical resection; Drug: Vincristine Sulfate; Given IV; Other Names: Kyocristine Leurocristine sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate
Experimental: Arm 3 (DHPLN) Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy.	Biological: Dactinomycin; Given IV; Other Names: Actinomycin A IV Actinomycin C1 ACTINOMYCIN D Actinomycin I1 Actinomycin IV Actinomycin X 1 Actinomycin-[thr-val-pro-sar-meval] Cosmegen DACT Dactinomycine Lyovac Cosmegen Meractinomycin ; Drug: Doxorubicin Hydrochloride; Given IV; Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex ; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy Irradiate Irradiated irradiation Radiation Radiotherapeutics RADIOTHERAPY RT Therapy, Radiation ; Procedure: Therapeutic Conventional Surgery; Undergo surgical resection; Drug: Vincristine Sulfate; Given IV; Other Names: Kyocristine Leurocristine sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate

Outcome Measures

Primary Outcome Measures

1. Event-Free Survival (EFS) [4 years from study enrollment]

   Probability of no relapse, secondary malignancy, or death whichever occurs first

2. Kidney Preservation After Preoperative Chemotherapy [12 weeks from study entry]

   Prevention of complete removal of at least one kidney in 50% of patients with bilateral Wilms tumor (BWT).

3. Number of Patients Without Complete Removal of at Least One Kidney [12 weeks from the study entry]

   To evaluate the efficacy of chemotherapy in preserving renal units in children with diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) and preventing Wilms tumor development.

4. Percentage of Patients Who Experienced Partial Nephrectomy After Preoperative Chemotherapy [12 weeks from study entry]

   Percentage of patients who experienced partial nephrectomy in lieu of nephrectomy in 25% of children with unilateral tumors and aniridia, Beckwith-Wiedemann syndrome (BWS), hemihypertrophy or other overgrowth syndromes, by using prenephrectomy 2-drug chemotherapy induction with vincristine and dactinomycin.

5. Percentage of Patients Who Had Definitive Surgical Treatment [12 weeks from study entry]

   Percentage of Bilateral Wilms Tumor (BWT) patients who undergo definitive surgery by week 12 after initiation of chemotherapy.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• The patient must have one of the following conditions to be eligible:

• Synchronous bilateral Wilms tumors**; or

• Unilateral Wilms tumor and aniridia, Beckwith-Wiedemann Syndrome, idiopathic hemihypertrophy, Simpson-Golabi-Behmel-Syndrome, Denys-Drash Syndrome or other associated genitourinary anomalies associated with bilateral Wilms tumor, such as hypospadias and undescended testis (to be eligible, these patients must not undergo any nephrectomy at diagnosis; note-horseshoe kidney is not associated with bilateral Wilms tumor and these patients should go on the appropriate unilateral Wilms tumor study); or

• Multicentric Wilms tumor (any age) (to be eligible, these patients must not undergo any nephrectomy at diagnosis); or

• Unilateral Wilms tumor with contralateral nephrogenic rest(s) (any size) in a child under one year of age (to be eligible, these patients must not undergo any nephrectomy at diagnosis); or

• Diffuse hyperplastic perilobar nephroblastomatosis (unilateral or bilateral) defined by central radiological review; or

• Wilms tumor arising in a solitary kidney (patients with metachronous Wilms tumor are not eligible)

• The AREN0534 study uses the guideline that Wilms tumor with a single lesion 1 cm or greater in the contralateral kidney or multiple lesions (of any size) in the contralateral kidney should be treated on the synchronous bilateral Wilms tumor stratum; patients with an isolated lesion less than 1 cm in the contralateral kidney should be treated on the appropriate study for unilateral Wilms tumor OR on the unilateral Wilms tumor/contralateral nephrogenic rest stratum of this study if they have not undergone nephrectomy and are under one year of age

• Loss of heterozygosity (LOH) results?which are used in the unilateral Wilms tumor studies?are not a requirement for enrollment on AREN0534; blood samples can be submitted but will not be used to direct AREN0534 therapy

• Specimens/materials must be submitted for central review by day 7; for enrollment on AREN0534, unless a biopsy was done, the submission requirements at enrollment on AREN03B2 refer to imaging studies; tissue samples are only required if a surgical procedure (biopsy or nephrectomy) was performed at the time of enrollment on AREN03B2

• Patients must begin protocol therapy on AREN0534 by day 14 following surgery or diagnosis by initial computed tomography (CT)/magnetic resonance imaging (MRI), unless medically contraindicated

• Karnofsky performance status must be >= 50% for patients > 16 years of age and Lansky performance status 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

• Patients with unilateral Wilms tumor and aniridia, Beckwith-Wiedemann Syndrome, idiopathic hemihypertrophy, Simpson-Golabi-Behmel-Syndrome, Denys-Drash Syndrome or other associated genitourinary anomalies; or multicentric or unilateral Wilms tumor with contralateral nephrogenic rest(s) (any size) in a child under 1 year of age who undergo a nephrectomy at diagnosis are not eligible for this study and should be directed to a unilateral Wilms tumor study

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

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

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

• (Cardiac function does not need to be assessed in patients who will not receive doxorubicin as part of their initial therapy on this study [i.e., patients who start on regimen EE-4A])

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

• Female patients who are lactating must agree to stop breastfeeding

• 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

• No concurrent aprepitant

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 Cancer Center	Birmingham	Alabama	United States	35233
3	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
4	The University of Arizona Medical Center-University Campus	Tucson	Arizona	United States	85724
5	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202-3591
6	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
7	Kaiser Permanente Downey Medical Center	Downey	California	United States	90242
8	Loma Linda University Medical Center	Loma Linda	California	United States	92354
9	Miller Children's and Women's Hospital Long Beach	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	Children's Hospital of Orange County	Orange	California	United States	92868
15	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
16	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
17	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
18	UCSF Medical Center-Parnassus	San Francisco	California	United States	94143
19	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
20	Children's Hospital Colorado	Aurora	Colorado	United States	80045
21	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado	United States	80218
22	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
23	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
24	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
25	Children's National Medical Center	Washington	District of Columbia	United States	20010
26	Broward Health Medical Center	Fort Lauderdale	Florida	United States	33316
27	Lee Memorial Health System	Fort Myers	Florida	United States	33901
28	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
29	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
30	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida	United States	32207
31	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
32	Miami Cancer Institute	Miami	Florida	United States	33176
33	Florida Hospital Orlando	Orlando	Florida	United States	32803
34	Arnold Palmer Hospital for Children	Orlando	Florida	United States	32806
35	Nemours Children's Clinic - Orlando	Orlando	Florida	United States	32806
36	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
37	Nemours Children's Hospital	Orlando	Florida	United States	32827
38	Nemours Children's Clinic - Pensacola	Pensacola	Florida	United States	32504
39	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701
40	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida	United States	33607
41	Saint Mary's Hospital	West Palm Beach	Florida	United States	33407
42	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
43	Augusta University Medical Center	Augusta	Georgia	United States	30912
44	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
45	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
46	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60611
47	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
48	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
49	Blank Children's Hospital	Des Moines	Iowa	United States	50309
50	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
51	Norton Children's Hospital	Louisville	Kentucky	United States	40202
52	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
53	Children's Hospital New Orleans	New Orleans	Louisiana	United States	70118
54	Eastern Maine Medical Center	Bangor	Maine	United States	04401
55	Maine Children's Cancer Program	Scarborough	Maine	United States	04074
56	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
57	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
58	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
59	Floating Hospital for Children at Tufts Medical Center	Boston	Massachusetts	United States	02111
60	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
61	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
62	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
63	Michigan State University Clinical Center	East Lansing	Michigan	United States	48824-7016
64	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
65	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
66	Kalamazoo Center for Medical Studies	Kalamazoo	Michigan	United States	49008
67	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
68	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
69	Mayo Clinic	Rochester	Minnesota	United States	55905
70	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
71	The Childrens Mercy Hospital	Kansas City	Missouri	United States	64108
72	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
73	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
74	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
75	Children's Specialty Center of Nevada II	Las Vegas	Nevada	United States	89109
76	Sunrise Hospital and Medical Center	Las Vegas	Nevada	United States	89109
77	Summerlin Hospital Medical Center	Las Vegas	Nevada	United States	89144
78	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
79	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
80	Saint Barnabas Medical Center	Livingston	New Jersey	United States	07039
81	Morristown Medical Center	Morristown	New Jersey	United States	07960
82	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
83	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
84	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
85	Overlook Hospital	Summit	New Jersey	United States	07902
86	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
87	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
88	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
89	NYU Winthrop Hospital	Mineola	New York	United States	11501
90	Mount Sinai Hospital	New York	New York	United States	10029
91	Columbia University/Herbert Irving Cancer Center	New York	New York	United States	10032
92	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
93	University of Rochester	Rochester	New York	United States	14642
94	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
95	Mission Hospital Inc-Memorial Campus	Asheville	North Carolina	United States	28801
96	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
97	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
98	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
99	Duke University Medical Center	Durham	North Carolina	United States	27710
100	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
101	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
102	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
103	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
104	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
105	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
106	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
107	Dayton Children's Hospital	Dayton	Ohio	United States	45404
108	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
109	Mercy Children's Hospital	Toledo	Ohio	United States	43608
110	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
111	Legacy Emanuel Children's Hospital	Portland	Oregon	United States	97227
112	Legacy Emanuel Hospital and Health Center	Portland	Oregon	United States	97227
113	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
114	Penn State Children's Hospital	Hershey	Pennsylvania	United States	17033
115	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
116	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134
117	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
118	Palmetto Health Richland	Columbia	South Carolina	United States	29203
119	BI-LO Charities Children's Cancer Center	Greenville	South Carolina	United States	29605
120	Greenville Cancer Treatment Center	Greenville	South Carolina	United States	29605
121	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
122	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
123	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
124	Texas Tech University Health Sciences Center-Amarillo	Amarillo	Texas	United States	79106
125	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
126	Medical City Dallas Hospital	Dallas	Texas	United States	75230
127	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
128	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
129	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
130	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
131	Covenant Children's Hospital	Lubbock	Texas	United States	79410
132	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
133	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
134	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
135	University of Vermont College of Medicine	Burlington	Vermont	United States	05405
136	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
137	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
138	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
139	Seattle Children's Hospital	Seattle	Washington	United States	98105
140	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
141	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington	United States	98405
142	Madigan Army Medical Center	Tacoma	Washington	United States	98431
143	West Virginia University Charleston Division	Charleston	West Virginia	United States	25304
144	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
145	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
146	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
147	Sydney Children's Hospital	Randwick	New South Wales	Australia	2031
148	The Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
149	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
150	Royal Children's Hospital-Brisbane	Herston	Queensland	Australia	4029
151	Lady Cilento Children's Hospital	South Brisbane	Queensland	Australia	4101
152	Women's and Children's Hospital-Adelaide	North Adelaide	South Australia	Australia	5006
153	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6008
154	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
155	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
156	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
157	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
158	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
159	Kingston Health Sciences Centre	Kingston	Ontario	Canada	K7L 2V7
160	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
161	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
162	The Montreal Children's Hospital of the MUHC	Montreal	Quebec	Canada	H3H 1P3
163	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
164	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4
165	Centre Hospitalier Universitaire de Quebec	Quebec		Canada	G1V 4G2
166	Schneider Children's Medical Center of Israel	Petah Tikua		Israel	49202
167	Starship Children's Hospital	Grafton	Auckland	New Zealand	1145
168	Christchurch Hospital	Christchurch		New Zealand	8011
169	San Jorge Children's Hospital	San Juan		Puerto Rico	00912

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Peter Ehrlich, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00945009
• Other Study ID Numbers: AREN0534; NCI-2011-01953; CDR0000649716; AREN0534; AREN0534; U10CA180886; U10CA098543
• First Posted: Jul 23, 2009
• Last Update Posted: Mar 25, 2022
• Last Verified: Mar 1, 2022

• Additional relevant MeSH terms: Neoplasms; Wilms Tumor; Rhabdoid Tumor; Kidney Neoplasms; Beckwith-Wiedemann Syndrome; Dactinomycin; Cactinomycin; Doxorubicin; Liposomal doxorubicin; Vincristine

Study Results

Participant Flow

Arm/Group Title	Arm 1 (Bilateral Wilms Tumors)	Arm 2 (Unilateral High Risk Tumors Bilaterally Predisposed)	Arm 3 (DHPLN)
Arm/Group Description	Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV	Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV	Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV
Period Title: Overall Study
STARTED	201	39	9
COMPLETED	156	32	6
NOT COMPLETED	45	7	3

Baseline Characteristics

Arm/Group Title	Arm 1 (Bilateral Wilms Tumors)	Arm 2 (Unilateral High Risk Tumors Bilaterally Predisposed)	Arm 3 (DHPLN)	Total
Arm/Group Description	Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV	Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV	Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV	Total of all reporting groups
Overall Participants	201	39	9	249
Age (Months) [Median (Standard Deviation) ]
Median (Standard Deviation) [Months]	32.03 (22.22)	34.70 (22.12)	13.26 (8.70)	31.78 (22.12)
Sex: Female, Male (Count of Participants)
Female	119 59.2%	23 59%	5 55.6%	147 59%
Male	82 40.8%	16 41%	4 44.4%	102 41%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	27 13.4%	3 7.7%	0 0%	30 12%
Not Hispanic or Latino	168 83.6%	35 89.7%	8 88.9%	211 84.7%
Unknown or Not Reported	6 3%	1 2.6%	1 11.1%	8 3.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 2.6%	0 0%	1 0.4%
Asian	3 1.5%	1 2.6%	0 0%	4 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	31 15.4%	5 12.8%	1 11.1%	37 14.9%
White	142 70.6%	29 74.4%	7 77.8%	178 71.5%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	25 12.4%	3 7.7%	1 11.1%	29 11.6%

Outcome Measures

1. Primary Outcome

Title	Event-Free Survival (EFS)
Description	Probability of no relapse, secondary malignancy, or death whichever occurs first
Time Frame	4 years from study enrollment

Outcome Measure Data

Analysis Population Description

All eligible BWT patients. 6 patients were excluded due to ineligibility and 6 patients were excluded due to protocol violation.

Arm/Group Title	Arm 1 (Bilateral Wilms Tumors)
Arm/Group Description	Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV
Measure Participants	189
Mean (95% Confidence Interval) [Probability]	0.82

2. Primary Outcome

Title	Kidney Preservation After Preoperative Chemotherapy
Description	Prevention of complete removal of at least one kidney in 50% of patients with bilateral Wilms tumor (BWT).
Time Frame	12 weeks from study entry

Outcome Measure Data

Analysis Population Description

Eligible and evaluable Bilateral Wilms Tumor patients who completed pre-nephrectomy chemotherapy (VAD). 49 patients who did not complete VAD were excluded.

Arm/Group Title	Arm 1 (Bilateral Wilms Tumors)
Arm/Group Description	Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV
Measure Participants	140
Number (95% Confidence Interval) [Percentage of patients]	39

3. Primary Outcome

Title	Number of Patients Without Complete Removal of at Least One Kidney
Description	To evaluate the efficacy of chemotherapy in preserving renal units in children with diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) and preventing Wilms tumor development.
Time Frame	12 weeks from the study entry

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients with diffuse hyperplastic perilobar nephroblastomatosis (DPHLN).

Arm/Group Title	Arm 3 (DHPLN)
Arm/Group Description	Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy.
Measure Participants	9
Count of Participants [Participants]	7 3.5%

4. Primary Outcome

Title	Percentage of Patients Who Experienced Partial Nephrectomy After Preoperative Chemotherapy
Description	Percentage of patients who experienced partial nephrectomy in lieu of nephrectomy in 25% of children with unilateral tumors and aniridia, Beckwith-Wiedemann syndrome (BWS), hemihypertrophy or other overgrowth syndromes, by using prenephrectomy 2-drug chemotherapy induction with vincristine and dactinomycin.
Time Frame	12 weeks from study entry

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients with unilateral high risk tumors who had partial or complete nephrectomy. 16 total patients were excluded (1 ineligible, 1 inevaluable, 1 violated protocol, and 13 did not have definitive surgery (partial or complete nephrectomy).

Arm/Group Title	Arm 2 (Unilateral High Risk Tumors Bilaterally Predisposed)
Arm/Group Description	Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV
Measure Participants	23
Number (95% Confidence Interval) [percentage of patients]	57

5. Primary Outcome

Title	Percentage of Patients Who Had Definitive Surgical Treatment
Description	Percentage of Bilateral Wilms Tumor (BWT) patients who undergo definitive surgery by week 12 after initiation of chemotherapy.
Time Frame	12 weeks from study entry

Outcome Measure Data

Analysis Population Description

Eligible and evaluable Bilateral Wilms Tumor patients. 6 patients were excluded due to ineligible and 6 patients were excluded due to protocol violation.

Arm/Group Title	Arm 1 (Bilateral Wilms Tumors)
Arm/Group Description	Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV
Measure Participants	189
Number (95% Confidence Interval) [percentage of participants]	85 42.3%

Adverse Events

Time Frame	From enrollment to up to 10 years of follow-up
Adverse Event Reporting Description	Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution, via expedited reporting (NCI AdEERs / CAeRs). The "AE Other" table reflects all CTCAEs collected excluding those that were reported as SAEs. Ineligible patients are excluded from reporting of adverse events.
Arm/Group Title	Arm 1 (Bilateral Wilms Tumors)		Arm 2 (Unilateral High Risk Tumors Bilaterally Predisposed)		Arm 3 (DHPLN)
Arm/Group Description	Patients start with three drug chemotherapy (Regimen VAD; vincristine, dactinomycin and doxorubicin) and are evaluated and six and 12 weeks for feasibility of undergoing a partial nephrectomy/renal sparing surgery. At week 12 definitive surgery takes place followed by chemotherapy and radiation therapy based on histology and stage. Treatment continues for 25 or 31 weeks depending on histology. Patients are followed for up to 10 years following end of therapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV		Patients start with either 2 drug or three drug chemotherapy (Regimen VA, VAD) and are evaluated a 6 and 12 weeks for feasibility of undergoing a partial nephrectomy. At week 12 definitive surgery takes place followed by chemotherapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV		Patients with this rare disease are diagnosed based on cross-sectional imaging characteristics and undergo 2 drug chemotherapy (Regimen;VA). Patients are reassessed at 6 weeks and 12 weeks. If disease has responded or stayed stable chemotherapy is completed for 19 weeks (Regimen EE4A). If disease has progress a biopsy is performed to assess histology and adjust therapy based on the biopsy. This therapy may include, nephrectomy, chemotherapy or radiation therapy. Dactinomycin: Given IV Doxorubicin Hydrochloride: Given IV Radiation Therapy: Undergo radiation therapy Therapeutic Conventional Surgery: Undergo surgical resection Vincristine Sulfate: Given IV
All Cause Mortality
	Arm 1 (Bilateral Wilms Tumors)		Arm 2 (Unilateral High Risk Tumors Bilaterally Predisposed)		Arm 3 (DHPLN)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/189 (5.3%)		0/36 (0%)		0/9 (0%)
Serious Adverse Events
	Arm 1 (Bilateral Wilms Tumors)		Arm 2 (Unilateral High Risk Tumors Bilaterally Predisposed)		Arm 3 (DHPLN)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/189 (6.3%)		1/36 (2.8%)		0/9 (0%)
General disorders
24600-Death NOS	8/189 (4.2%)	8	0/36 (0%)	0	0/9 (0%)	0
Hepatobiliary disorders
40600-Hepatobiliary disorders - Other specify	3/189 (1.6%)	3	1/36 (2.8%)	1	0/9 (0%)	0
Investigations
11600-Alanine aminotransferase increased	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
15000-Aspartate aminotransferase increased	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
83600-Urine output decreased	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
Metabolism and nutrition disorders
43100-Hypokalemia	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
Respiratory, thoracic and mediastinal disorders
71500-Respiratory failure	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm 1 (Bilateral Wilms Tumors)		Arm 2 (Unilateral High Risk Tumors Bilaterally Predisposed)		Arm 3 (DHPLN)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/189 (18%)		1/36 (2.8%)		0/9 (0%)
Blood and lymphatic system disorders
13200-Anemia	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
33300-Febrile neutropenia	3/189 (1.6%)	4	0/36 (0%)	0	0/9 (0%)	0
Cardiac disorders
20100-Cardiac disorders - Other specify	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
78900-Supraventricular tachycardia	1/189 (0.5%)	2	0/36 (0%)	0	0/9 (0%)	0
Gastrointestinal disorders
10300-Abdominal pain	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
23400-Constipation	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
75700-Small intestinal obstruction	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
87900-Vomiting	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
Infections and infestations
18800-Bronchial infection	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
73700-Sepsis	3/189 (1.6%)	3	0/36 (0%)	0	0/9 (0%)	0
83100-Urinary tract infection	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
Investigations
11600-Alanine aminotransferase increased	1/189 (0.5%)	1	1/36 (2.8%)	2	0/9 (0%)	0
15000-Aspartate aminotransferase increased	2/189 (1.1%)	2	1/36 (2.8%)	2	0/9 (0%)	0
24100-Creatinine increased	4/189 (2.1%)	6	0/36 (0%)	0	0/9 (0%)	0
28600-Ejection fraction decreased	1/189 (0.5%)	2	0/36 (0%)	0	0/9 (0%)	0
58300-Neutrophil count decreased	6/189 (3.2%)	8	0/36 (0%)	0	0/9 (0%)	0
65800-Platelet count decreased	2/189 (1.1%)	4	0/36 (0%)	0	0/9 (0%)	0
83600-Urine output decreased	2/189 (1.1%)	2	0/36 (0%)	0	0/9 (0%)	0
88500-White blood cell decreased	2/189 (1.1%)	2	0/36 (0%)	0	0/9 (0%)	0
Metabolism and nutrition disorders
10700-Acidosis	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
11900-Alkalosis	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
24700-Dehydration	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
41400-Hyperglycemia	2/189 (1.1%)	2	0/36 (0%)	0	0/9 (0%)	0
41600-Hyperkalemia	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
42500-Hyperuricemia	2/189 (1.1%)	2	0/36 (0%)	0	0/9 (0%)	0
42700-Hypocalcemia	4/189 (2.1%)	4	1/36 (2.8%)	1	0/9 (0%)	0
42900-Hypoglycemia	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
43100-Hypokalemia	5/189 (2.6%)	6	1/36 (2.8%)	1	0/9 (0%)	0
43200-Hypomagnesemia	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
43500-Hypophosphatemia	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
Nervous system disorders
14000-Aphonia	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
63900-Peripheral motor neuropathy	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
72500-Reversible posterior leukoencephalopathy syndrome	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
Renal and urinary disorders
11100-Acute kidney injury	3/189 (1.6%)	3	0/36 (0%)	0	0/9 (0%)	0
71000-Renal and urinary disorders - Other specify	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
Respiratory, thoracic and mediastinal disorders
14100-Apnea	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
15400-Atelectasis	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
27800-Dyspnea	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
43900-Hypoxia	2/189 (1.1%)	2	1/36 (2.8%)	1	0/9 (0%)	0
50700-Laryngeal edema	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
51300-Laryngeal stenosis	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
66300-Pneumonitis	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
68700-Pulmonary edema	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
71500-Respiratory failure	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
78100-Stridor	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
Vascular disorders
42100-Hypertension	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0
79600-Thromboembolic event	1/189 (0.5%)	1	0/36 (0%)	0	0/9 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.