Combination Chemotherapy in Treating Children With Progressive Brain Tumors

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00002944

Collaborator

National Cancer Institute (NCI) (NIH)

428

Enrollment

204

Locations

Arms

180

Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: This randomized phase III trial is studying two different combination chemotherapy regimens and comparing how well they work in treating children with low-grade astrocytomas or other residual tumors of the brain.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumors Central Nervous System Tumors	Drug: carboplatin Drug: lomustine Drug: procarbazine hydrochloride Drug: thioguanine Drug: vincristine sulfate	Phase 3

Detailed Description

OBJECTIVES:

Compare the event free survival as a result of treatment with carboplatin and vincristine versus thioguanine, procarbazine, lomustine, and vincristine in children with progressive brain tumors.
Estimate tumor response rates to each regimen of chemotherapy in these patients.
Determine toxic effects and quality of life of children treated with each regimen of chemotherapy.
Investigate biological and clinical factors which may predict tumor response and early progression (tumor size, location, pathologic subtype, cytogenetics, and proliferative index by MIB-1 (Ki67)) in these patients.
Investigate factors contributing to neuropsychological and endocrine status of children with brain tumors treated without irradiation.

OUTLINE: This is a randomized study. Patients are stratified according to site of disease, status at entry, and pathology. Patients are randomized to one of two treatment arms. Patients with neurofibromatosis are nonrandomly assigned to arm II.

Arm I: Patients receive induction with carboplatin and vincristine for 10 weeks followed by 2 weeks of rest. Induction is followed by 8 courses of maintenance beginning on day 84 of induction or upon hematopoietic recovery. Each course consists of 4 weekly doses of carboplatin and 3 weekly doses of vincristine (given concurrently with the first 3 weeks of carboplatin), followed by 2 weeks of rest.
Arm II: Patients receive oral thioguanine, procarbazine, and lomustine on days 0-4, followed by vincristine IV on days 14 and 28. Treatment continues every 6 weeks for a maximum of 8 courses.

PROJECTED ACCRUAL: A total of 280-340 patients will be accrued over 4 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

428 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Chemotherapy for Progressive Low Grade Astrocytoma in Children Less Than Ten Years Old

Study Start Date :

Apr 1, 1997

Actual Primary Completion Date :

Feb 1, 2006

Actual Study Completion Date :

Apr 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Regimen A (CV Chemotherapy) Induction will consist of 10 weeks of therapy (carboplatin, vincristine sulfate),followed by 2 weeks without chemotherapy. Induction should only be interrupted in the event of grade 3 neurotoxicity, grade 2 renal toxicity, grade 4 hematologic toxicity, or tumor progression. Maintenance-Four Courses (2 cycles/course) commences on Day 84 (week 12) of Induction or when peripheral counts recover with ANC >1,000/$L and platelet count >100,000/$L. Each cycle will consist of 4 weekly doses of carboplatin, three weekly doses of vincristine sulfate (given concomitantly with the first 3 weeks of carboplatin), followed by two weeks of rest for a total of 6 weeks. Maintenance will continue for a total of 8 cycles.	Drug: carboplatin Given IV Other Names: Paraplatin NSC-241240 Drug: vincristine sulfate Given PO and IV Other Names: Oncovin NSC-675574
Experimental: Regimen B (TPCV Chemotherapy) Each cycle of chemotherapy consists of 4 days of oral chemotherapy (Thioguanine, procarbazine hydrochloride, Lomustine and Vincristine sulfate beginning Day 0, followed by vincristine sulfate IV on Days 14 and 28. The cycle is repeated every 6 weeks (42 days). A total of 8 cycles will be given.	Drug: lomustine Given IV Other Names: CCNU NSC-79037 Drug: procarbazine hydrochloride Given PO Other Names: Matulane NSC-77213 Drug: thioguanine Given PO Other Names: 6-TG NSC-752 Drug: vincristine sulfate Given PO and IV Other Names: Oncovin NSC-675574

Arm

Intervention/Treatment

Experimental: Regimen A (CV Chemotherapy)

Induction will consist of 10 weeks of therapy (carboplatin, vincristine sulfate),followed by 2 weeks without chemotherapy. Induction should only be interrupted in the event of grade 3 neurotoxicity, grade 2 renal toxicity, grade 4 hematologic toxicity, or tumor progression. Maintenance-Four Courses (2 cycles/course) commences on Day 84 (week 12) of Induction or when peripheral counts recover with ANC >1,000/$L and platelet count >100,000/$L. Each cycle will consist of 4 weekly doses of carboplatin, three weekly doses of vincristine sulfate (given concomitantly with the first 3 weeks of carboplatin), followed by two weeks of rest for a total of 6 weeks. Maintenance will continue for a total of 8 cycles.

Drug: carboplatin

Given IV

Other Names:

Paraplatin

NSC-241240

Drug: vincristine sulfate

Given PO and IV

Other Names:

Oncovin

NSC-675574

Experimental: Regimen B (TPCV Chemotherapy)

Each cycle of chemotherapy consists of 4 days of oral chemotherapy (Thioguanine, procarbazine hydrochloride, Lomustine and Vincristine sulfate beginning Day 0, followed by vincristine sulfate IV on Days 14 and 28. The cycle is repeated every 6 weeks (42 days). A total of 8 cycles will be given.

Drug: lomustine

Given IV

Other Names:

CCNU

NSC-79037

Drug: procarbazine hydrochloride

Given PO

Other Names:

Matulane

NSC-77213

Drug: thioguanine

Given PO

Other Names:

6-TG

NSC-752

Drug: vincristine sulfate

Given PO and IV

Other Names:

Oncovin

NSC-675574

Outcome Measures

Primary Outcome Measures

Event Free Survival [Time from study entry until disease progression, death without progression of disease, occurrence of a second malignant neoplasm or last follow-up, whichever comes first, assessed up to 5 years]
Compare the event-free survival as a result of treatment with either CV or TPCV

Secondary Outcome Measures

Survival [5 years]
Defined as the time to death from any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 9 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Pathologically confirmed low grade residual astrocytomas or other eligible residual tumors of the brain interpreted as low grade (WHO grades I and II) such as the following:
Glial Tumors
Astrocytic tumors
Low grade astrocytoma (variants: fibrillary, protoplasmic, gemistocytic)
Pilocytic astrocytoma
Pleomorphic xanthoastrocytomas
Subependymal giant cell astrocytoma
Infantile desmoplastic astrocytoma
Low grade oligodendroglial tumors
Low grade oligodendroglioma
Low grade mixed gliomas
Oligo-astrocytoma
Neuronal Tumors
Ganglioglioma (excluding tumors with anaplastic astrocytic components)
Infantile desmoplastic ganglioglioma
Chiasmatic-hypothalamic tumor without histologic confirmation
All of the following diagnostic tests (radiological or clinical evidence of progression, surgery, or confirmatory MRI) must be carried out within 6 weeks of enrollment into this study
Progressive disease following surgical excision based on clear radiological or clinical evidence of progression, or an incomplete excision (less than 95% or greater than 1.5 cm2) with necessity to begin treatment because of a risk of neurologic impairment with progression
Chiasmatic lesions that have contiguous extensions of tumor into other regions of the visual pathways demonstrated on contrast MRI will be eligible for study without histopathological confirmation
Patients with neurofibromatosis who have radiographic diagnosis of chiasmatic-hypothalamic tumor are eligible for the study, without requiring a biopsy confirmation of tumor histology, but not unless tumor progression is documented radiographically
No intrinsic brain stem tumors of the pons or isolated optic nerve tumors without definitive involvement of the optic chiasm

PATIENT CHARACTERISTICS:

Age:

Under 10

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count greater than 1,000/mm^3 (arm II)
Platelet count greater than 100,000/mm^3 (arm II)

Hepatic:

Not specified

Renal:

Creatinine less than 1.5 times upper limit of normal for age OR
Creatinine clearance or radioisotope GFR greater than 70 mL/min or equivalent GFR as determined by the institutional normal range

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior chemotherapy for the tumor

Endocrine therapy:

Prior corticosteroid therapy allowed

Radiotherapy:

No prior radiotherapy for the tumor

Surgery:

See Disease characteristics

Other:

Prior diuretic therapy allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama	United States	36604
2	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016-7710
3	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Southern California Permanente Medical Group	Downey	California	United States	90027
5	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
6	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California	United States	92354
7	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California	United States	90801
8	Childrens Hospital Los Angeles	Los Angeles	California	United States	90027
9	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center	Los Angeles	California	United States	90048-1865
10	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781
11	Children's Hospital Central California	Madera	California	United States	93638-8762
12	Children's Hospital and Research Center Oakland	Oakland	California	United States	94609
13	Children's Hospital of Orange County	Orange	California	United States	92868
14	Lucile Packard Children's Hospital at Stanford University Medical Center	Palo Alto	California	United States	95798
15	Sutter Cancer Center	Sacramento	California	United States	95816
16	University of California Davis Cancer Center	Sacramento	California	United States	95817
17	Kaiser Permanente Medical Center - Oakland	Sacramento	California	United States	95825
18	Rady Children's Hospital - San Diego	San Diego	California	United States	92123-4282
19	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
20	Santa Barbara Cottage Children's Hospital	Santa Barbara	California	United States	93105
21	Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	California	United States	95051-5386
22	Children's Hospital Center for Cancer and Blood Disorders	Aurora	Colorado	United States	80045
23	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut	United States	06360-2875
24	Yale Cancer Center	New Haven	Connecticut	United States	06520-8028
25	Alfred I. duPont Hospital for Children	Wilmington	Delaware	United States	19803
26	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
27	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
28	Broward General Medical Center Cancer Center	Fort Lauderdale	Florida	United States	33316
29	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida	United States	33901
30	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0232
31	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida	United States	33021
32	Nemours Children's Clinic	Jacksonville	Florida	United States	32207
33	Miami Children's Hospital	Miami	Florida	United States	33155
34	Baptist-South Miami Regional Cancer Program	Miami	Florida	United States	33176
35	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida	United States	32803-1273
36	M.D. Anderson Cancer Center at Orlando	Orlando	Florida	United States	32806
37	Nemours Children's Clinic - Orlando	Orlando	Florida	United States	32806
38	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida	United States	32504
39	All Children's Hospital	Saint Petersburg	Florida	United States	33701
40	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida	United States	33607
41	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida	United States	33407
42	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus	Atlanta	Georgia	United States	30322
43	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus	Atlanta	Georgia	United States	30342
44	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912-3730
45	Medical Center of Central Georgia	Macon	Georgia	United States	31208
46	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
47	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
48	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho	United States	83712-6297
49	University of Illinois Cancer Center	Chicago	Illinois	United States	60612-7243
50	Rush University Medical Center	Chicago	Illinois	United States	60612
51	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60614
52	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
53	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
54	Keyser Family Cancer Center at Advocate Hope Children's Hospital	Oak Lawn	Illinois	United States	60453
55	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois	United States	60068-1174
56	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
57	Swedish-American Regional Cancer Center	Rockford	Illinois	United States	61104-2315
58	Simmons Cooper Cancer Institute	Springfield	Illinois	United States	62794-9677
59	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
60	St. Vincent Indianapolis Hospital	Indianapolis	Indiana	United States	46260
61	Blank Children's Hospital	Des Moines	Iowa	United States	50309
62	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1002
63	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
64	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
65	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
66	Wesley Medical Center	Wichita	Kansas	United States	67214
67	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky	United States	40536-0093
68	Kosair Children's Hospital	Louisville	Kentucky	United States	40232
69	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana	United States	71315-3198
70	Children's Hospital of New Orleans	New Orleans	Louisiana	United States	70118
71	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
72	CancerCare of Maine at Eastern Maine Medical Center	Bangor	Maine	United States	04401
73	Maine Children's Cancer Program at Barbara Bush Children's Hospital	Scarborough	Maine	United States	04074-9308
74	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
75	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland	United States	21215
76	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
77	Baystate Regional Cancer Program at D'Amour Center for Cancer Care	Springfield	Massachusetts	United States	01199-0001
78	C.S. Mott Children's Hospital at University of Michigan Medical Center	Ann Arbor	Michigan	United States	48109-0286
79	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
80	Hurley Medical Center	Flint	Michigan	United States	48503
81	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503-2560
82	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
83	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-5381
84	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan	United States	48910
85	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
86	CCOP - Duluth	Duluth	Minnesota	United States	55805-1983
87	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
88	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota	United States	55455
89	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
90	Children's Hospitals and Clinics of Minnesota - St. Paul	St. Paul	Minnesota	United States	55102-2392
91	University of Mississippi Cancer Clinic	Jackson	Mississippi	United States	39216-4505
92	Keesler Air Force Base Medical Center	Keesler AFB	Mississippi	United States	39534-2511
93	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
94	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
95	Cardinal Glennon Children's Hospital	St. Louis	Missouri	United States	63104
96	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	St. Louis	Missouri	United States	63110
97	Children's Hospital	Omaha	Nebraska	United States	68114-4113
98	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89109-2306
99	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey	United States	07601
100	St. Barnabas Medical Center Cancer Center	Livingston	New Jersey	United States	07039
101	Overlook Hospital	Morristown	New Jersey	United States	07962
102	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
103	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
104	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
105	St. Joseph's Hospital and Medical Center	Paterson	New Jersey	United States	07503
106	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
107	Albany Medical Center Hospital	Albany	New York	United States	12208-3419
108	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York	United States	10461
109	Maimonides Cancer Center at Maimonides Medical Center	Brooklyn	New York	United States	11219
110	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
111	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York	United States	11030
112	Schneider Children's Hospital	New Hyde Park	New York	United States	11040
113	Beth Israel Medical Center - Petrie Division	New York	New York	United States	10003-3803
114	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
115	St. Luke's - Roosevelt Hospital Center - St.Luke's Division	New York	New York	United States	10027
116	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York	United States	10032
117	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
118	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
119	Stony Brook University Cancer Center	Stony Brook	New York	United States	11794-9446
120	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
121	New York Medical College	Valhalla	New York	United States	10595
122	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
123	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
124	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
125	Dakota Cancer Institute at Dakota Clinic - South University	Fargo	North Dakota	United States	58103-4940
126	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
127	Akron Children's Hospital	Akron	Ohio	United States	44308-1062
128	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
129	Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106-5000
130	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
131	Nationwide Children's Hospital	Columbus	Ohio	United States	43205-2696
132	Dayton Children's - Dayton	Dayton	Ohio	United States	45404-1815
133	Toledo Hospital	Toledo	Ohio	United States	43606
134	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
135	Tod Children's Hospital	Youngstown	Ohio	United States	44501
136	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
137	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon	United States	97227
138	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon	United States	97239-3098
139	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
140	Penn State Children's Hospital	Hershey	Pennsylvania	United States	17033-0850
141	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104-9786
142	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134-1095
143	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15213
144	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
145	Palmetto Health South Carolina Cancer Center	Columbia	South Carolina	United States	29203
146	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
147	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
148	East Tennessee Children's Hospital	Knoxville	Tennessee	United States	37901
149	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838
150	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas	United States	79106
151	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
152	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
153	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104
154	University of Texas Medical Branch	Galveston	Texas	United States	77555-0361
155	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
156	Wilford Hall Medical Center	Lackland AFB	Texas	United States	78236-5300
157	Covenant Children's Hospital	Lubbock	Texas	United States	79410
158	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78207
159	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229-3993
160	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
161	Primary Children's Medical Center	Salt Lake City	Utah	United States	84113-1100
162	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
163	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042-3300
164	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507-1971
165	Naval Medical Center - Portsmouth	Portsmouth	Virginia	United States	23708-2197
166	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037
167	Carilion Medical Center for Children at Roanoke Community Hospital	Roanoke	Virginia	United States	24014
168	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
169	Group Health Central Hospital	Seattle	Washington	United States	98112
170	Deaconess Medical Center	Spokane	Washington	United States	99210-0248
171	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington	United States	99220-2555
172	Mary Bridge Children's Hospital and Health Center - Tacoma	Tacoma	Washington	United States	98405
173	Madigan Army Medical Center - Tacoma	Tacoma	Washington	United States	98431
174	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia	United States	25302
175	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia	United States	25701
176	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia	United States	26506
177	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
178	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601
179	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
180	John Hunter Hospital	Newcastle	New South Wales	Australia	2310
181	Prince of Wales Private Hospital	Randwick	New South Wales	Australia	2031
182	Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
183	Royal Children's Hospital	Brisbane	Queensland	Australia	4029
184	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
185	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
186	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 1Z2
187	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia	Canada	V6H 3V4
188	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
189	Janeway Children's Health and Rehabilitation Centre	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
190	IWK Health Centre	Halifax	Nova Scotia	Canada	B3J 3G9
191	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
192	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	K7L 2V7
193	Children's Hospital of Western Ontario	London	Ontario	Canada	N6A 5W9
194	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
195	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
196	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec	Canada	H3H 1P3
197	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5
198	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan	Canada	S4T 7T1
199	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan	Canada	S7N 4H4
200	Centre Hospitalier Universitaire de Quebec	Quebec		Canada	G1V 4G2
201	University Medical Center Groningen	Groningen		Netherlands	9713 EZ
202	Starship Children's Health	Auckland		New Zealand	1
203	Swiss Pediatric Oncology Group Bern	Bern		Switzerland	3010
204	Swiss Pediatric Oncology Group Geneva	Geneva		Switzerland	1205