Vincristine, Dactinomycin, and Doxorubicin With or Without Radiation Therapy or Observation Only in Treating Younger Patients Who Are Undergoing Surgery for Newly Diagnosed Stage I, Stage II, or Stage III Wilms' Tumor

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00352534
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 808
• Locations: 221
• Arms: 3
• Anticipated Duration (Months): 206
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase III trial is studying vincristine, dactinomycin, and doxorubicin with or without radiation therapy or observation only to see how well they work in treating patients undergoing surgery for newly diagnosed stage I, stage II, or stage III Wilms' tumor. Drugs used in chemotherapy, such as vincristine, dactinomycin, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving these treatments after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient.

Condition or Disease	Intervention/Treatment	Phase
Stage I Wilms Tumor; Stage II Wilms Tumor; Stage III Wilms Tumor	Procedure: therapeutic conventional surgery; Drug: vincristine sulfate; Biological: dactinomycin; Drug: doxorubicin hydrochloride; Radiation: 3-dimensional conformal radiation therapy	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. Evaluate the overall and event-free survival of younger patients with newly diagnosed stage I favorable histology Wilms' tumor (< 2 years of age and < 550gms) treated with nephrectomy only (very low risk), or with newly diagnosed stage III favorable histology Wilms tumor with possible nephrectomy followed by vincristine, dactinomycin, doxorubicin hydrochloride, and radiotherapy (standard risk).

SECONDARY OBJECTIVES:

1. Determine the effects of adding doxorubicin hydrochloride to the regimen for patients with stage I or II favorable histology found to have a high-risk biological marker.

2. Determine whether the omission of adjuvant therapy increases the incidence of contralateral kidney lesions in patients with very low-risk disease treated by nephrectomy and observation only.

3. Determine whether the omission of adjuvant therapy increases the incidence of renal failure in patients with very low-risk disease who have metachronous relapse.

4. Correlate study outcomes in patients with standard-risk disease with biological data from tissue collections on protocol study COG-AREN03B2.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical and biological risk factors (very low risk vs standard risk).

STRATUM I: (very low-risk disease) Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks.

STRATUM II: (standard-risk, stage I or II disease with adverse biological marker) Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks.

STRATUM III: (standard-risk, stage III disease) Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks.

After completion of study treatment, patients are followed periodically for up to 8 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 808 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment for Very Low and Standard Risk Favorable Histology Wilms Tumor
• Actual Study Start Date: Oct 30, 2006
• Actual Primary Completion Date: Dec 31, 2014
• Anticipated Study Completion Date: Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nephrectomy and re-evaluation (very low-risk disease) Patients undergo nephrectomy only. If they meet criteria, they are then observed periodically for 5 years. Patients with recurrent disease undergo surgery (immediate or delayed) and receive chemotherapy as in stratum III. Patients with no metachronous renal disease receive radiotherapy. Patients with metachronous disease undergo renal-sparing surgery and chemotherapy as in stratum III, but no radiotherapy. Treatment continues for up to 25 weeks.	Procedure: therapeutic conventional surgery; Undergo surgery; Drug: vincristine sulfate; Given IV; Other Names: leurocristine sulfate VCR Vincasar PFS ; Biological: dactinomycin; Given IV; Other Names: ACT-D actinomycin C1 AD Cosmegen DACT ; Drug: doxorubicin hydrochloride; Given IV; Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF ; Radiation: 3-dimensional conformal radiation therapy; Patients undergo radiotherapy; Other Names: 3D conformal radiation therapy 3D-CRT
Experimental: Nephrectomy, chemotherapy (standard-risk, stg I or II) Patients undergo nephrectomy. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1, every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 doses of doxorubicin. Treatment continues for up to 25 weeks.	Procedure: therapeutic conventional surgery; Undergo surgery; Drug: vincristine sulfate; Given IV; Other Names: leurocristine sulfate VCR Vincasar PFS ; Biological: dactinomycin; Given IV; Other Names: ACT-D actinomycin C1 AD Cosmegen DACT ; Drug: doxorubicin hydrochloride; Given IV; Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF ; Radiation: 3-dimensional conformal radiation therapy; Patients undergo radiotherapy; Other Names: 3D conformal radiation therapy 3D-CRT
Experimental: Nephrectomy/biopsy, chemotherapy (standard-risk, stage III) Patients undergo nephrectomy, if feasible, or biopsy. For patients who undergo biopsy only, definitive surgery is undertaken at week 7 or 13. Between 9 and 14 days post-nephrectomy, patients receive vincristine IV beginning on day 1 every week for 10 weeks then every 3 weeks for a total of 15 doses. Patients receive dactinomycin IV beginning day 1, alternating every 3 weeks with doxorubicin hydrochloride IV for a total of 5 doses of dactinomycin and 4 dose of doxorubicin hydrochloride. Patients undergo radiotherapy over 5-7 days after nephrectomy. Treatment continues for up to 25 weeks.	Procedure: therapeutic conventional surgery; Undergo surgery; Drug: vincristine sulfate; Given IV; Other Names: leurocristine sulfate VCR Vincasar PFS ; Biological: dactinomycin; Given IV; Other Names: ACT-D actinomycin C1 AD Cosmegen DACT ; Drug: doxorubicin hydrochloride; Given IV; Other Names: ADM ADR Adria Adriamycin PFS Adriamycin RDF ; Radiation: 3-dimensional conformal radiation therapy; Patients undergo radiotherapy; Other Names: 3D conformal radiation therapy 3D-CRT

Outcome Measures

Primary Outcome Measures

1. Event Free Survival Probability [4 years]

   Probability of no relapse, secondary malignancy, or death after 4 year in the study.

2. Overall Survival (OS) Probability [4 years]

   Probability of being alive after 4 years in the study.

Secondary Outcome Measures

1. Incidence of Contralateral Kidney Lesions [During follow-up]

   Number of contralateral kidney lesions during follow-up.

2. Incidence of Renal Failure [During follow-up]

   Number of renal failures defined as requiring dialysis or renal transplant as determined by low GFR during follow-up

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed Wilms' tumor

• Newly diagnosed stage I-III disease

• Favorable histology

• No moderate- or high-risk Wilms' predisposition syndromes

• Must meet 1 of the following disease stratification categories:

• Very low-risk disease

• Stage I disease

• Age < 2 years

• Tumor weight < 550 g

• Regional lymph nodes histologically negative (must have been sampled)

• No pulmonary metastases on CT scan of chest

• No synchronous bilateral Wilms tumors (Stage V)

• Not predisposed to develop bilateral Wilms tumors, defined as unilateral

Wilms tumor and any of the following:

• Aniridia

• Beckwith-Wiedemann syndrome

• Simpson-Golabi-Behmel syndrome

• Denys-Drash syndrome or other associated genito-urinary anomalies

• Multicentric WT or unilateral WT with contralateral nephrogenic rest(s) in a child < 1 year of age

• Diffuse hyperplastic perilobar nephroblastomatosis

• Standard-risk disease meeting 1 of the following criteria:

• Disease does not require radiotherapy

• LOH at chromosomes 1p and 16q for stage I or II

• Stage I disease meeting 1 of the following criteria:

• Age ≥ 2 years to age < 30 years

• Tumor weight ≥ 500 g

• Stage II disease

• Age < 30 years

• Any tumor weight

• Disease requires radiotherapy

• No LOH at chromosomes 1p and 16q*

• Stage III disease

• Must be enrolled on protocol COG-AREN03B2

• Karnofsky performance status (PS) 50-100% for patients > 16 years old

• Lansky PS 50-100% for patients ≤ 16 years old

• Bilirubin (direct) ≤ 1.5 times upper limit of normal (ULN)

• AST or ALT < 2.5 times ULN

• Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram (standard-risk disease)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patient must use effective contraception

• No prior tumor-directed chemotherapy or radiotherapy

• Patients transferring from AREN03B2 with LOH 1p and 16q allowed

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	35294
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	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
12	Children's Hospital Central California	Madera	California	United States	93636-8762
13	Children's Hospital and Research Center at Oakland	Oakland	California	United States	94609-1809
14	Kaiser Permanente-Oakland	Oakland	California	United States	94611
15	Childrens Hospital of Orange County	Orange	California	United States	92868-3874
16	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
17	University of California at Davis Cancer Center	Sacramento	California	United States	95817
18	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
19	University of California San Francisco Medical Center-Parnassus	San Francisco	California	United States	94143
20	Santa Barbara Cottage Hospital	Santa Barbara	California	United States	93102
21	Children's Hospital Colorado	Aurora	Colorado	United States	80045
22	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado	United States	80218
23	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
24	Yale University	New Haven	Connecticut	United States	06520
25	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
26	Children's National Medical Center	Washington	District of Columbia	United States	20010
27	Lombardi Comprehensive Cancer Center at Georgetown University	Washington	District of Columbia	United States	20057
28	Broward Health Medical Center	Fort Lauderdale	Florida	United States	33316
29	Lee Memorial Health System	Fort Myers	Florida	United States	33901
30	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
31	University of Florida	Gainesville	Florida	United States	32610
32	Memorial Healthcare System - Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
33	Nemours Children's Clinic - Jacksonville	Jacksonville	Florida	United States	32207
34	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
35	Miami Children's Hospital	Miami	Florida	United States	33155
36	Baptist Hospital of Miami	Miami	Florida	United States	33176
37	Florida Hospital	Orlando	Florida	United States	32803
38	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
39	Nemours Children's Hospital	Orlando	Florida	United States	32827
40	Nemours Children's Clinic - Pensacola	Pensacola	Florida	United States	32504
41	All Children's Hospital	Saint Petersburg	Florida	United States	33701
42	Saint Joseph Children's Hospital of Tampa	Tampa	Florida	United States	33607
43	Saint Mary's Hospital	West Palm Beach	Florida	United States	33407
44	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
45	Georgia Regents University	Augusta	Georgia	United States	30912
46	Memorial Health University Medical Center	Savannah	Georgia	United States	31403
47	University of Hawaii	Honolulu	Hawaii	United States	96813
48	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
49	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
50	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60611
51	University of Illinois	Chicago	Illinois	United States	60612
52	University of Chicago	Chicago	Illinois	United States	60637
53	Loyola University Medical Center	Maywood	Illinois	United States	60153
54	Advocate Children's Hospital-Oak Lawn	Oak Lawn	Illinois	United States	60453
55	Advocate Lutheran General Hospital.	Park Ridge	Illinois	United States	60068
56	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61602
57	Southern Illinois University	Springfield	Illinois	United States	62702
58	Indiana University Medical Center	Indianapolis	Indiana	United States	46202
59	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
60	Saint Vincent Hospital and Health Services	Indianapolis	Indiana	United States	46260
61	Blank Children's Hospital	Des Moines	Iowa	United States	50309
62	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
63	University of Kentucky	Lexington	Kentucky	United States	40536
64	Kosair Children's Hospital	Louisville	Kentucky	United States	40202
65	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
66	Children's Hospital-Main Campus	New Orleans	Louisiana	United States	70118
67	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
68	Eastern Maine Medical Center	Bangor	Maine	United States	04401
69	Maine Children's Cancer Program	Scarborough	Maine	United States	04074
70	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
71	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
72	Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21287
73	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
74	Floating Hospital for Children at Tufts Medical Center	Boston	Massachusetts	United States	02111
75	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
76	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
77	Baystate Medical Center	Springfield	Massachusetts	United States	01199
78	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
79	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
80	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
81	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
82	Michigan State University Clinical Center	East Lansing	Michigan	United States	48824-7016
83	Hurley Medical Center	Flint	Michigan	United States	48502
84	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
85	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
86	Kalamazoo Center for Medical Studies	Kalamazoo	Michigan	United States	49008
87	Beaumont Children's Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
88	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
89	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota	United States	55455
90	Mayo Clinic	Rochester	Minnesota	United States	55905
91	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
92	Columbia Regional	Columbia	Missouri	United States	65201
93	The Childrens Mercy Hospital	Kansas City	Missouri	United States	64108
94	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
95	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
96	Saint John's Mercy Medical Center	Saint Louis	Missouri	United States	63141
97	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska	United States	68114
98	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
99	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
100	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
101	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
102	Saint Barnabas Medical Center	Livingston	New Jersey	United States	07039
103	Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
104	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
105	UMDNJ - Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
106	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
107	Saint Joseph's Regional Medical Center	Paterson	New Jersey	United States	07503
108	Overlook Hospital	Summit	New Jersey	United States	07902
109	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87106
110	University of New Mexico	Albuquerque	New Mexico	United States	87106
111	Albany Medical Center	Albany	New York	United States	12208
112	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467-2490
113	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
114	Winthrop University Hospital	Mineola	New York	United States	11501
115	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York	United States	11040
116	New York University Langone Medical Center	New York	New York	United States	10016
117	Mount Sinai Medical Center	New York	New York	United States	10029
118	Columbia University Medical Center	New York	New York	United States	10032
119	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
120	Weill Medical College of Cornell University	New York	New York	United States	10065
121	University of Rochester	Rochester	New York	United States	14642
122	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
123	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
124	New York Medical College	Valhalla	New York	United States	10595
125	Mission Hospital-Memorial Campus	Asheville	North Carolina	United States	28801
126	University of North Carolina	Chapel Hill	North Carolina	United States	27599
127	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
128	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
129	Duke University Medical Center	Durham	North Carolina	United States	27710
130	East Carolina University	Greenville	North Carolina	United States	27858
131	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
132	Sanford Medical Center-Fargo	Fargo	North Dakota	United States	58122
133	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
134	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
135	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
136	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
137	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
138	Dayton Children's Hospital	Dayton	Ohio	United States	45404
139	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
140	Mercy Children's Hospital	Toledo	Ohio	United States	43608
141	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
142	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma	United States	74136
143	Legacy Emanuel Children's Hospital	Portland	Oregon	United States	97227
144	Legacy Emanuel Hospital and Health Center	Portland	Oregon	United States	97227
145	Oregon Health and Science University	Portland	Oregon	United States	97239
146	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
147	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-2001
148	Penn State Hershey Children's Hospital	Hershey	Pennsylvania	United States	17033
149	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
150	Children's Oncology Group	Philadelphia	Pennsylvania	United States	19104
151	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134
152	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
153	Rhode Island Hospital	Providence	Rhode Island	United States	02903
154	Medical University of South Carolina	Charleston	South Carolina	United States	29425
155	Palmetto Health Richland	Columbia	South Carolina	United States	29203
156	BI-LO Charities Children's Cancer Center	Greenville	South Carolina	United States	29605
157	Greenville Cancer Treatment Center	Greenville	South Carolina	United States	29605
158	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
159	T C Thompson Children's Hospital	Chattanooga	Tennessee	United States	37403
160	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
161	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
162	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
163	Texas Tech University Health Science Center-Amarillo	Amarillo	Texas	United States	79106
164	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
165	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
166	Medical City Dallas Hospital	Dallas	Texas	United States	75230
167	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
168	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
169	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
170	Baylor College of Medicine	Houston	Texas	United States	77030
171	M D Anderson Cancer Center	Houston	Texas	United States	77030
172	Covenant Children's Hospital	Lubbock	Texas	United States	79410
173	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
174	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
175	Scott and White Memorial Hospital	Temple	Texas	United States	76508
176	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
177	University of Vermont	Burlington	Vermont	United States	05401
178	University of Virginia	Charlottesville	Virginia	United States	22908
179	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
180	Childrens Hospital-King's Daughters	Norfolk	Virginia	United States	23507
181	Naval Medical Center - Portsmouth	Portsmouth	Virginia	United States	23708-2197
182	Virginia Commonwealth University	Richmond	Virginia	United States	23298
183	Carilion Clinic Children's Hospital	Roanoke	Virginia	United States	24014
184	Seattle Children's Hospital	Seattle	Washington	United States	98105
185	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
186	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington	United States	98405
187	Madigan Army Medical Center	Tacoma	Washington	United States	98431
188	West Virginia University Charleston	Charleston	West Virginia	United States	25304
189	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
190	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
191	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
192	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
193	Sydney Children's Hospital	Randwick	New South Wales	Australia	2031
194	The Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
195	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
196	Royal Childrens Hospital	Herston	Queensland	Australia	4029
197	Women's and Children's Hospital-Adelaide	North Adelaide	South Australia	Australia	5006
198	Royal Children's Hospital	Parkville	Victoria	Australia	3052
199	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6008
200	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
201	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
202	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
203	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
204	Janeway Child Health Centre	Saint John's	Newfoundland and Labrador	Canada	A1B 3V6
205	IWK Health Centre	Halifax	Nova Scotia	Canada	B3J 3G9
206	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
207	Chedoke-McMaster Hospitals	Hamilton	Ontario	Canada	L8S 4L8
208	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	K7L 5P9
209	Children's Hospital	London	Ontario	Canada	N6A 5W9
210	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
211	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
212	The Montreal Children's Hospital of the MUHC	Montreal	Quebec	Canada	H3H 1P3
213	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
214	Centre Hospitalier Universitaire de Quebec	Ste-Foy	Quebec	Canada	G1V 4G2
215	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
216	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4
217	Schneider Children's Medical Center of Israel	Petah Tikua		Israel	49202
218	Starship Children's Hospital	Grafton	Auckland	New Zealand	1145
219	Christchurch Hospital	Christchurch		New Zealand	8011
220	San Jorge Children's Hospital	San Juan		Puerto Rico	00912
221	Swiss Pediatric Oncology Group - Bern	Bern		Switzerland	3010

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Conrad Fernandez, MD, 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: NCT00352534
• Other Study ID Numbers: AREN0532; NCI-2009-01067; CDR0000487540; AREN0532; AREN0532; U10CA098543
• First Posted: Jul 14, 2006
• Last Update Posted: Jan 13, 2022
• Last Verified: Jan 1, 2022

• Additional relevant MeSH terms: Neoplasms; Wilms Tumor; Dactinomycin; Cactinomycin; Doxorubicin; Liposomal doxorubicin; Vincristine

Study Results

Participant Flow

Arm/Group Title	Stage I/II	Stage III	Very Low Risk Disease	Low Risk, Stage I or II, no LOH	Standard Risk, Stage I or II With LOH	Standard Risk, Stage III	High Risk
Arm/Group Description	Patients who have either Very Low Risk Disease, Low Risk Stage I or II no LOH, and Standard Risk, Stage I or II with LOH prior to final Risk Group Assignment	Patients who have either Standard Risk, Stage III and High Risk Patients prior to final Risk Group Assignment.	Treatment arm. Nephrectomy and re-evaluation,very low-risk disease.	Treatment arm. Low risk, stage I or II, no loss of heterozygosity (LOH).	Treatment arm. Standard Risk, Stage I or II with LOH.	Treatment arm. Standard Risk, Stage III.	Treatment arm. High risk.
Period Title: Initial Staging
STARTED	211	597	0	0	0	0	0
COMPLETED	203	588	0	0	0	0	0
NOT COMPLETED	8	9	0	0	0	0	0
Period Title: Initial Staging
STARTED	0	0	119	52	32	548	40
COMPLETED	0	0	116	49	31	503	1
NOT COMPLETED	0	0	3	3	1	45	39

Baseline Characteristics

Arm/Group Title	Stage I or II	Stage III	Total
Arm/Group Description	Patients who have either Very Low Risk Disease, Low Risk Stage I or II no LOH, and Standard Risk, Stage I or II with LOH prior to final Risk Group Assignment.	Patients who have either Standard Risk, Stage III and High Risk Patients prior to final Risk Group Assignment.	Total of all reporting groups
Overall Participants	211	597	808
Age (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	23.91 (24.37)	50.62 (30.89)	43.64 (31.83)
Sex: Female, Male (Count of Participants)
Female	110 52.1%	318 53.3%	428 53%
Male	101 47.9%	279 46.7%	380 47%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	38 18%	89 14.9%	127 15.7%
Not Hispanic or Latino	165 78.2%	482 80.7%	647 80.1%
Unknown or Not Reported	8 3.8%	26 4.4%	34 4.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.5%	6 1%	7 0.9%
Asian	2 0.9%	15 2.5%	17 2.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	39 18.5%	89 14.9%	128 15.8%
White	141 66.8%	417 69.8%	558 69.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	28 13.3%	70 11.7%	98 12.1%

Outcome Measures

1. Primary Outcome

Title	Event Free Survival Probability
Description	Probability of no relapse, secondary malignancy, or death after 4 year in the study.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Eligible very low risk or standard risk patients

Arm/Group Title	Very Low Risk	Standard Risk, Stage I or II, With LOH	Standard Risk, Stage III
Arm/Group Description	Very Low Risk	Standard Risk, Stage I or II, with LOH	Standard Risk, Stage III
Measure Participants	116	32	535
Number (95% Confidence Interval) [Probability]	0.88	0.87	0.88

2. Primary Outcome

Title	Overall Survival (OS) Probability
Description	Probability of being alive after 4 years in the study.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

Eligible very low risk or standard risk patients

Arm/Group Title	Very Low Risk	Standard Risk, Stage I or II, With LOH	Standard Risk, Stage III
Arm/Group Description	Very Low Risk	Standard Risk, Stage I or II, with LOH	Standard Risk, Stage III
Measure Participants	116	32	535
Number (95% Confidence Interval) [Probability]	1.00	1.00	0.97

3. Secondary Outcome

Title	Incidence of Contralateral Kidney Lesions
Description	Number of contralateral kidney lesions during follow-up.
Time Frame	During follow-up

Outcome Measure Data

Analysis Population Description

Very low risk patients treated by nephrectomy and observation only.

Arm/Group Title	Very Low Risk
Arm/Group Description	Very Low Risk
Measure Participants	116
Number [Lesions]	1

4. Secondary Outcome

Title	Incidence of Renal Failure
Description	Number of renal failures defined as requiring dialysis or renal transplant as determined by low GFR during follow-up
Time Frame	During follow-up

Outcome Measure Data

Analysis Population Description

Very low risk patients that have metachronous relapse.

Arm/Group Title	Very Low Risk
Arm/Group Description	Very Low Risk
Measure Participants	116
Number [Incidents]	0

Adverse Events

Adverse Event Reporting Description	Adverse Events were reported for eligible patients only.
Arm/Group Title	Very Low Risk Disease		Low Risk, Stage I or II, no LOH		Standard Risk, Stage I or II, With LOH		Standard Risk, Stage III		High Risk
Arm/Group Description	Nephrectomy and Re-evaluation		Low risk, stage I or II, no loss of heterozygosity (LOH).		Standard Risk, Stage I or II, with loss of heterozygosity (LOH).		Nephrectomy/Biopsy, Chemotherapy		High risk.
All Cause Mortality
	Very Low Risk Disease		Low Risk, Stage I or II, no LOH		Standard Risk, Stage I or II, With LOH		Standard Risk, Stage III		High Risk
	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)
Serious Adverse Events
	Very Low Risk Disease		Low Risk, Stage I or II, no LOH		Standard Risk, Stage I or II, With LOH		Standard Risk, Stage III		High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/116 (0%)		0/51 (0%)		0/32 (0%)		20/535 (3.7%)		1/40 (2.5%)
Gastrointestinal disorders
36700-Gastrointestinal disorders - Other specify	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
75700-Small intestinal obstruction	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
General disorders
24600-Death NOS	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	10/535 (1.9%)	10	0/40 (0%)	0
37200-General disorders and administration site conditions	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
55700-Multi-organ failure	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
Hepatobiliary disorders
40000-Hepatic failure	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
Infections and infestations
73700-Sepsis	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	2/535 (0.4%)	3	0/40 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
51900-Leukemia secondary to oncology chemotherapy	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
58000-Neoplasms benign malignant and unspecified (incl cy	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	3/535 (0.6%)	3	1/40 (2.5%)	1
Nervous system disorders
73600-Seizure	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
Other (Not Including Serious) Adverse Events
	Very Low Risk Disease		Low Risk, Stage I or II, no LOH		Standard Risk, Stage I or II, With LOH		Standard Risk, Stage III		High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/116 (0%)		2/51 (3.9%)		0/32 (0%)		31/535 (5.8%)		0/40 (0%)
Blood and lymphatic system disorders
33300-Febrile neutropenia	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
Gastrointestinal disorders
14900-Ascites	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	2/535 (0.4%)	2	0/40 (0%)	0
36400-Gastritis	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
75700-Small intestinal obstruction	0/116 (0%)	0	1/51 (2%)	1	0/32 (0%)	0	0/535 (0%)	0	0/40 (0%)	0
87900-Vomiting	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
General disorders
33900-Fever	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
Hepatobiliary disorders
40600-Hepatobiliary disorders - Other specify	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
Infections and infestations
44800-Infections and infestations - Other specify	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	2/535 (0.4%)	4	0/40 (0%)	0
73700-Sepsis	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
Injury, poisoning and procedural complications
47000-Intraoperative gastrointestinal injury	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
66800-Postoperative hemorrhage	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
Investigations
11600-Alanine aminotransferase increased	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	5/535 (0.9%)	6	0/40 (0%)	0
15000-Aspartate aminotransferase increased	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	6/535 (1.1%)	6	0/40 (0%)	0
58300-Neutrophil count decreased	0/116 (0%)	0	1/51 (2%)	1	0/32 (0%)	0	7/535 (1.3%)	9	0/40 (0%)	0
Metabolism and nutrition disorders
41400-Hyperglycemia	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	2	0/40 (0%)	0
41600-Hyperkalemia	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
42500-Hyperuricemia	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	2/535 (0.4%)	2	0/40 (0%)	0
42700-Hypocalcemia	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
42900-Hypoglycemia	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	2/535 (0.4%)	2	0/40 (0%)	0
43100-Hypokalemia	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	7/535 (1.3%)	8	0/40 (0%)	0
Renal and urinary disorders
71300-Renal hemorrhage	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
Respiratory, thoracic and mediastinal disorders
71500-Respiratory failure	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	2/535 (0.4%)	2	0/40 (0%)	0
71600-Respiratory thoracic and mediastinal disorders - Ot	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
Vascular disorders
43600-Hypotension	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	1/535 (0.2%)	1	0/40 (0%)	0
79600-Thromboembolic event	0/116 (0%)	0	0/51 (0%)	0	0/32 (0%)	0	2/535 (0.4%)	2	0/40 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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