High-Dose Interferon Alfa in Treating Patients With Stage II or Stage III Melanoma

• Sponsor: ECOG-ACRIN Cancer Research Group (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00003641
• Collaborator: National Cancer Institute (NCI) (NIH), Southwest Oncology Group (Other), Cancer and Leukemia Group B (Other), NCIC Clinical Trials Group (Other), Children's Oncology Group (Other)
• Enrollment: 1,150
• Locations: 533
• Arms: 2
• Duration (Months): 322
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Interferon alfa may interfere with the growth of cancer cells. It is not yet known whether treatment with interferon alfa is more effective than observation alone for stage II or stage III melanoma that has been completely removed surgically.

PURPOSE: This randomized phase III trial is studying high dose interferon alfa to see how well it works compared to observation only in treating patients with stage II or stage III melanoma that has been completely removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: interferon alfa-2b; Other: observation	Phase 3

Detailed Description

OBJECTIVES:

Primary Objective:

• Compare the effect of high-dose interferon alfa-2b treatment on the relapse-free survival of patients with stage II or III resected malignant melanoma.

Secondary Objectives:

• Compare the effect of this treatment regimen on overall survival of these patients.

• Assess the toxicity of this treatment in these patients.

• Compare the effect of treatment on quality of life.

OUTLINE: This is a randomized study. Patients are stratified by pathologic lymph node status (known vs unknown),lymph node staging procedures(sentinel lymph node procedure vs. elective lymph node dissection vs. no lymphadenectomy), Breslow depth (<= 1.0 mm vs. 1.01-2.0 mm vs. 2.01-4.0 mm vs > 4.0 mm), ulceration of the primary lesion (yes vs. no vs. unknown), and disease stage (lymph node positive [N1, N2a] vs. lymph node negative [N0]). Patients are randomized into one of two treatment arms in a 1:1 ratio.

• Arm I (observation): Patients undergo observation for 4 weeks.

• Arm II (Interferon Alfa-2b): Patients receive high-dose interferon alfa-2b intravenously (IV) over 20 minutes daily for 5 consecutive days. Treatment repeats weekly for 4 weeks in the absence of unacceptable toxicity.

Quality of life is assessed before treatment, at day 22, every 3 months for 2 years, and then every 6 months for 3 years.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter until 15 years after randomization.

PROJECTED ACCRUAL: A total of 1,420 patients will be accrued for this study over 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Randomized Study of Four Weeks of High Dose Interferon Alfa-2b in Stage T2bN0, T3a-bN0, T4a-bN0, and T1-4, N1a,2a (Microscopic) Melanoma
• Study Start Date: Dec 1, 1998
• Actual Primary Completion Date: Jan 1, 2015
• Anticipated Study Completion Date: Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: Observation Patients undergo observation for 4 weeks.	Other: observation; Patients undergo observation for 4 weeks.; Other Names: clinical observation
Experimental: Interferon Alfa-2b Patients receive high-dose interferon alfa-2b IV over 20 minutes daily for 5 consecutive days. Treatment repeats weekly for 4 weeks in the absence of unacceptable toxicity.	Biological: interferon alfa-2b; Given IV; Other Names: recombinant interferon alfa Intron-A IFN-α 2b NSC # 377523

Outcome Measures

Primary Outcome Measures

1. 5-year Relapse-free Survival Rate [assessed every 3 months for 2 years, every 6 months for 3 years]

   Relapse-free survival (RFS) was defined as time from randomization to disease relapse or death from any cause, whichever occurred first. Patients without disease relapse were censored at last disease assessment date known of free of relapse. Kaplan-Meier method was used to estimate 5-year RFS rate in the intent-to-treat (ITT) patients.

Secondary Outcome Measures

1. 5-year Overall Survival Rate [assessed every 3 months for 2 years, every 6 months for 3 years]

   Overall survival (OS) was defined as time from randomization to death from any cause. Patients still alive were censored at last known alive date. Kaplan-Meier method was used to estimate 5-year OS rate in the ITT patients.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed primary melanoma of cutaneous origin

• Stage II (T3 N0 M0 1.5-4.0 mm Breslow depth)

• Clinically negative regional lymph node pathologic status unknown OR

• Histologically negative regional lymph nodes

• Stage III (T4 N0 M0)

• Greater than 4.0 mm Breslow depth OR

• Stage III (T1-4 N1)

• One lymph node positive microscopically

• Patients must meet at least 1 of the following criteria:

• T2b N0 - primary melanoma 1.01-2.0 mm with ulceration, node negative

• T3a-b N0 - primary melanoma 2.01-4.0 mm with and without ulceration, node negative

• T4a-b N0 - primary melanoma > 4.0 mm with or without ulceration, node negative

• T1a N1a-2a (microscopic) - primary melanoma of any thickness with microscopically positive lymph node (any number)

• Patients with a positive sentinel node should undergo complete lymphadenectomy of the nodal basin prior to study

• Must complete all primary therapy (wide excision with or without lymphadenectomy) and be randomized in this study within 84 days of wide excision

• Must have undergone an adequate wide excision of the primary lesion

• Age 18 and over (For ECOG patients only, patients must be >=10 years)

• Eastern Cooperative Oncology Group (ECOG) Performance status of 0-1

• Adequate hematopoietic, hepatic, and renal function based on the following tests:

• White blood cell (WBC) cout at least 3,000/mm^3

• Platelet count at least 125,000/mm^3

• Hematocrit at least 30%

• Bilirubin no greater than 2 times upper limit of normal (ULN)

• Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase no greater than 2 times ULN

• If lactate dehydrogenase or alkaline phosphatase is above normal, a contrast-enhanced computed tomography (CT) scan or Magnetic resonance imaging (MRI) of the liver is required to document the absence of tumor

• Blood urea nitrogen (BUN) no greater than 33 mg/dL OR Creatinine no greater than 1.8 mg/dL

• No other concurrent or prior malignancies within the past 5 years except:

• Cancer in situ

• Lobular carcinoma in situ of the breast

• Carcinoma in situ of the cervix

• Atypical melanocytic hyperplasia or Clark 1 melanoma in situ

• Basal or squamous cell skin cancer

• Negative pregnancy test

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

Exclusion Criteria:

• Clinical, radiological/laboratory, or pathological evidence of incompletely resected melanoma or any distant metastatic disease

• Clinically palpable lymphadenopathy

• Evidence of organic brain syndrome or significant impairment of basal cognitive function or any psychiatric disorder that would preclude study participation

• Other significant medical or surgical condition, or any medication or treatment regimens, that would interfere with study participation

• Pregnant or nursing

• Other history of invasive melanoma

• Autoimmune disorders or conditions of immunosuppression

• History of active ischemic heart disease

• Cerebrovascular disease

• Congestive heart failure (New York Heart Association class III or IV heart disease)

• Prior or concurrent chemotherapy

• Prior immunotherapy including tumor vaccines, interferon, interleukins, levamisole, or other biologic response modifiers for melanoma

• Concurrent systemic corticosteroids including oral steroids (i.e., prednisone, dexamethasone), topical steroid creams or ointments, or any steroid-containing inhalers

• Prior or concurrent radiotherapy

• Other concurrent immunosuppressive medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Comprehensive Cancer Center	Birmingham	Alabama	United States	35294
2	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama	United States	36688
3	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724-5024
4	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center	Fort Smith	Arkansas	United States	72903
5	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
6	Kaiser Permanente - Deer Valley	Antioch	California	United States	94531
7	Alta Bates Summit Comprehensive Cancer Center	Berkeley	California	United States	94704
8	Peninsula Medical Center	Burlingame	California	United States	94010
9	Southern California Permanente Medical Group	Downey	California	United States	90027
10	Kaiser Permanente - Fremont	Fremont	California	United States	94538
11	Marin Cancer Institute at Marin General Hospital	Greenbrae	California	United States	94904
12	Kaiser Permanente Medical Center - Hayward	Hayward	California	United States	94545
13	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California	United States	92354
14	Kaiser Permanente Medical Center - Oakland	Oakland	California	United States	94611
15	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California	United States	94304
16	Kaiser Permanente Medical Center - Redwood City	Redwood City	California	United States	94063
17	Kaiser Permanente Medical Center - Richmond	Richmond	California	United States	94801
18	Kaiser Permanente Medical Center - Roseville	Roseville	California	United States	95661
19	Sutter Cancer Center at Roseville Medical Center	Roseville	California	United States	95661
20	Sutter Cancer Center	Sacramento	California	United States	95816
21	South Sacramento Kaiser-Permanente Medical Center	Sacramento	California	United States	95823
22	Kaiser Permanente Medical Center - Sacramento	Sacramento	California	United States	95825
23	Kaiser Permanente Medical Office -Vandever Medical Office	San Diego	California	United States	92120
24	Naval Medical Center - San Diego	San Diego	California	United States	92134
25	Kaiser Permanente Medical Center - San Francisco Geary Campus	San Francisco	California	United States	94115
26	California Pacific Medical Center - California Campus	San Francisco	California	United States	94118
27	Kaiser Permanente Medical Center - Santa Teresa	San Jose	California	United States	95119
28	Kaiser Foundation Hospital - San Rafael	San Rafael	California	United States	94903
29	Sutter Health - Western Division Cancer Research Group	San Rafael	California	United States	94903
30	Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	California	United States	95051
31	Kaiser Permanente Medical Center - Santa Rosa	Santa Rosa	California	United States	95403
32	Kaiser Permanente Medical Center - South San Francisco	South San Francisco	California	United States	94080
33	Stanford Cancer Center	Stanford	California	United States	94305-5824
34	Kaiser Permanente Medical Facility - Stockton	Stockton	California	United States	95210
35	Kaiser Permanente Medical Center - Vallejo	Vallejo	California	United States	94589
36	Sutter Solano Medical Center	Vallejo	California	United States	94589
37	Kaiser Permanente Medical Center - Walnut Creek	Walnut Creek	California	United States	94596
38	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
39	Boulder Community Hospital	Boulder	Colorado	United States	80301-9019
40	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
41	St. Anthony Central Hospital	Denver	Colorado	United States	80204
42	Kaiser Permanente - Denver	Denver	Colorado	United States	80205
43	Porter Adventist Hospital	Denver	Colorado	United States	80210
44	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
45	St. Joseph Hospital	Denver	Colorado	United States	80218
46	Rose Medical Center	Denver	Colorado	United States	80220
47	CCOP - Colorado Cancer Research Program	Denver	Colorado	United States	80224-2522
48	Swedish Medical Center	Englewood	Colorado	United States	80110
49	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado	United States	81502
50	North Colorado Medical Center	Greeley	Colorado	United States	80631
51	Kaiser Permanente - Lafayette	Lafayette	Colorado	United States	80026
52	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
53	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80501
54	McKee Medical Center	Loveland	Colorado	United States	80539
55	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado	United States	81004
56	North Suburban Medical Center	Thornton	Colorado	United States	80229
57	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
58	Praxair Cancer Center at Danbury Hospital	Danbury	Connecticut	United States	06810
59	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
60	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
61	Carl and Dorothy Bennett Cancer Center at Stamford Hospital	Stamford	Connecticut	United States	06904
62	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
63	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
64	Herbert D. Kerman Regional Oncology Center - Daytona Beach	Daytona Beach	Florida	United States	32114
65	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
66	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida	United States	32207
67	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida	United States	33458
68	Lakeland Regional Cancer Center at Lakeland Regional Medical Center	Lakeland	Florida	United States	33805
69	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
70	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida	United States	33136
71	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida	United States	32504
72	West Florida Cancer Institute at West Florida Hospital - Pensacola	Pensacola	Florida	United States	32514
73	All Children's Hospital	Saint Petersburg	Florida	United States	33701
74	Florida Cancer Specialists - Sarasota Downtown	Sarasota	Florida	United States	34236
75	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida	United States	33407
76	Piedmont Hospital	Atlanta	Georgia	United States	30309
77	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus	Atlanta	Georgia	United States	30322
78	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
79	Northside Hospital Cancer Center	Atlanta	Georgia	United States	30342-1611
80	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia	United States	30342-1701
81	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342
82	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912
83	WellStar Cobb Hospital	Austell	Georgia	United States	30106
84	John B. Amos Cancer Center	Columbus	Georgia	United States	31904
85	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia	United States	30033
86	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia	United States	30033
87	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
88	Gwinnett Medical Center	Lawrenceville	Georgia	United States	30045
89	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
90	Southern Regional Medical Center	Riverdale	Georgia	United States	30274-2600
91	Harbin Clinic Cancer Center - Medical Oncology	Rome	Georgia	United States	30165
92	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia	United States	31405
93	Kaiser Permanente - Moanalua Medical Center and Clinic	Honolulu	Hawaii	United States	96819
94	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
95	Hematology Oncology Associates of Illinois - Berwyn	Berwyn	Illinois	United States	60402
96	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
97	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
98	Saint Joseph Hospital	Chicago	Illinois	United States	60657
99	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
100	Crossroads Cancer Center	Effingham	Illinois	United States	62401
101	Evanston Hospital	Evanston	Illinois	United States	60201-1781
102	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
103	Kellogg Cancer Care Center	Highland Park	Illinois	United States	60035
104	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois	United States	60521
105	Midwest Center for Hematology/Oncology	Joliet	Illinois	United States	60432
106	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois	United States	60048
107	La Grange Oncology Associates - Geneva	Naperville	Illinois	United States	60563
108	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois	United States	60714
109	Swedish-American Regional Cancer Center	Rockford	Illinois	United States	61104-2315
110	Hematology Oncology Associates - Skokie	Skokie	Illinois	United States	60076
111	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
112	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
113	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
114	Elkhart Clinic, LLC	Elkhart	Indiana	United States	46514-2098
115	Michiana Hematology-Oncology, PC - Elkhart	Elkhart	Indiana	United States	46514
116	Elkhart General Hospital	Elkhart	Indiana	United States	46515
117	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
118	William N. Wishard Memorial Hospital	Indianapolis	Indiana	United States	46202
119	Howard Community Hospital	Kokomo	Indiana	United States	46904
120	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
121	Michiana Hematology Oncology PC - La Porte	La Porte	Indiana	United States	46350
122	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
123	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana	United States	46545-1470
124	Saint Joseph Regional Medical Center	Mishawaka	Indiana	United States	46545-1470
125	Cancer Center at Ball Memorial Hospital	Muncie	Indiana	United States	47303-3499
126	Medical Consultants, PC at Ball Memorial Cancer Center	Muncie	Indiana	United States	47303
127	Michiana Hematology Oncology PC - Plymouth	Plymouth	Indiana	United States	46563
128	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
129	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
130	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
131	South Bend Clinic	South Bend	Indiana	United States	46617
132	McFarland Clinic, PC	Ames	Iowa	United States	50010
133	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
134	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
135	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
136	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa	United States	52803
137	Genesis Medical Center - West Campus	Davenport	Iowa	United States	52804
138	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
139	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
140	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
141	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
142	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
143	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
144	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
145	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
146	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
147	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
148	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
149	Covenant Cancer Treatment Center	Waterloo	Iowa	United States	50702
150	Hospital District Sixth of Harper County	Anthony	Kansas	United States	67003
151	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
152	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
153	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
154	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
155	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
156	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
157	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
158	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67905
159	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
160	Menorah Medical Center	Overland Park	Kansas	United States	66209
161	Saint Luke's Hospital - South	Overland Park	Kansas	United States	66213
162	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
163	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
164	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
165	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas	United States	67401
166	Shawnee Mission Medical Center	Shawnee Mission	Kansas	United States	66204
167	Cotton-O'Neil Cancer Center	Topeka	Kansas	United States	66606
168	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
169	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
170	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
171	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
172	CCOP - Wichita	Wichita	Kansas	United States	67214
173	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
174	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
175	Cancer Care at Our Lady of Bellefonte Hospital	Ashland	Kentucky	United States	41101
176	Drs. Carrol, Sheth, Raghavan	Louisville	Kentucky	United States	40215
177	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana	United States	71315-3198
178	Ochsner Health Center - Bluebonnet	Baton Rouge	Louisiana	United States	70809
179	Louisiana State University Health Sciences Center - Monroe	Monroe	Louisiana	United States	71210
180	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
181	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
182	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana	United States	71130-3932
183	Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Scarborough	Maine	United States	04074
184	DeCesaris Cancer Institute at Anne Arundel Medical Center	Annapolis	Maryland	United States	21401
185	Greater Baltimore Medical Center Cancer Center	Baltimore	Maryland	United States	21204
186	Union Hospital Cancer Program at Union Hospital	Elkton	Maryland	United States	21921
187	Tufts-NEMC Cancer Center	Boston	Massachusetts	United States	02111
188	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
189	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
190	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
191	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
192	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
193	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
194	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
195	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
196	Hurley Medical Center	Flint	Michigan	United States	48503
197	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
198	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
199	Foote Memorial Hospital	Jackson	Michigan	United States	49201
200	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
201	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
202	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
203	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan	United States	48144
204	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
205	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
206	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
207	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
208	Michiana Hematology Oncology PC - Niles	Niles	Michigan	United States	49120
209	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
210	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
211	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
212	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
213	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
214	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan	United States	49085
215	St. John Macomb Hospital	Warren	Michigan	United States	48093
216		Alexandria	Minnesota	United States	56308
217	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
218	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
219	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
220	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
221	CCOP - Duluth	Duluth	Minnesota	United States	55805
222	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
223	St. Luke's Hospital Cancer Care Center	Duluth	Minnesota	United States	55805
224	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
225	Fergus Falls Medical Group, PA	Fergus Falls	Minnesota	United States	56537
226	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
227	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
228	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
229	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
230	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
231	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
232	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
233	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
234	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
235	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
236	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
237	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
238	United Hospital	Saint Paul	Minnesota	United States	55102
239	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
240	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
241	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
242	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
243	University of Mississippi Cancer Clinic	Jackson	Mississippi	United States	39216-4505
244	Saint Luke's Hospital	Chesterfield	Missouri	United States	63017
245	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
246	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
247	Truman Medical Center - Hospital Hill	Kansas City	Missouri	United States	64108
248	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri	United States	64111
249	St. Joseph Medical Center	Kansas City	Missouri	United States	64114
250	North Kansas City Hospital	Kansas City	Missouri	United States	64116
251	Heartland Hematology Oncology Associates, Incorporated	Kansas City	Missouri	United States	64118
252	CCOP - Kansas City	Kansas City	Missouri	United States	64131
253	Research Medical Center	Kansas City	Missouri	United States	64132
254	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
255	Liberty Hospital	Liberty	Missouri	United States	64068
256	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
257	Saint Joseph Oncology, Incorporated	Saint Joseph	Missouri	United States	64507
258	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
259	Arch Medical Services, Incorporated at Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
260	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
261	St. John's Regional Health Center	Springfield	Missouri	United States	65804
262	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
263	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
264	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
265	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
266	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
267	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
268	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
269	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
270	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
271	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
272	Northern Montana Hospital	Havre	Montana	United States	59501
273	St. Peter's Hospital	Helena	Montana	United States	59601
274	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
275	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
276	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
277	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
278	Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center	Grand Island	Nebraska	United States	68803
279	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
280	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
281	Immanuel Medical Center	Omaha	Nebraska	United States	68122
282	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
283	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
284	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-6805
285	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
286	Norris Cotton Cancer Center at Catholic Medical Center	Manchester	New Hampshire	United States	03102
287	Hunterdon Regional Cancer Center at Hunterdon Medical Center	Flemington	New Jersey	United States	08822
288	CCOP - Northern New Jersey	Hackensack	New Jersey	United States	07601
289	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey	United States	07601
290	Cancer Institute of New Jersey at Hamilton	Hamilton	New Jersey	United States	08690
291	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
292	Frederick R. and Betty M. Smith Cancer Treatment Center	Sparta	New Jersey	United States	07871
293	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
294	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
295	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
296	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York	United States	12801
297	Monter Cancer Center of the North Shore-LIJ Health System	Lake Success	New York	United States	11042
298	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
299	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York	United States	11030
300	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
301	Stony Brook University Cancer Center	Stony Brook	New York	United States	11794-9446
302	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
303	Randolph Hospital	Asheboro	North Carolina	United States	27203-5400
304	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
305	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
306	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
307	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
308	Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	North Carolina	United States	27403-1198
309	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina	United States	27834
310	Annie Penn Cancer Center	Reidsville	North Carolina	United States	27320
311	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
312	MeritCare Broadway	Fargo	North Dakota	United States	58122
313	Akron Children's Hospital	Akron	Ohio	United States	44308-1062
314	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
315	Barberton Citizens Hospital	Barberton	Ohio	United States	44203
316	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
317	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
318	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio	United States	44708
319	Aultman Cancer Center at Aultman Hospital	Canton	Ohio	United States	44710-1799
320	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
321	Christ Hospital Cancer Center	Cincinnati	Ohio	United States	45219
322	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
323	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
324	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio	United States	44109
325	North Coast Cancer Care - Clyde	Clyde	Ohio	United States	43410
326	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210-1240
327	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
328	CCOP - Columbus	Columbus	Ohio	United States	43215
329	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
330	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
331	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
332	Dayton Children's - Dayton	Dayton	Ohio	United States	45404
333	Grandview Hospital	Dayton	Ohio	United States	45405
334	Good Samaritan Hospital	Dayton	Ohio	United States	45406
335	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
336	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
337	CCOP - Dayton	Dayton	Ohio	United States	45420
338	Grady Memorial Hospital	Delaware	Ohio	United States	43015
339	Community Cancer Center	Elyria	Ohio	United States	44035
340	Hematology Oncology Center	Elyria	Ohio	United States	44035
341	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
342	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
343	Wayne Hospital	Greenville	Ohio	United States	45331
344	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
345	Fairfield Medical Center	Lancaster	Ohio	United States	43130
346	St. Rita's Medical Center	Lima	Ohio	United States	45801
347	Lima Memorial Hospital	Lima	Ohio	United States	45804
348	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
349	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
350	St. Luke's Hospital	Maumee	Ohio	United States	43537
351	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
352	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
353	Fisher-Titus Medical Center	Norwalk	Ohio	United States	44857
354	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
355	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
356	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
357	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
358	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
359	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
360	Toledo Hospital	Toledo	Ohio	United States	43606
361	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
362	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
363	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
364	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
365	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
366	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
367	Fulton County Health Center	Wauseon	Ohio	United States	43567
368	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
369	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
370	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
371	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
372	Cleo Craig Cancer Research Clinic	Lawton	Oklahoma	United States	73505
373	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
374	Cancer Care Associates - Mercy Campus	Oklahoma City	Oklahoma	United States	73120
375	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
376	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
377	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon	United States	97210
378	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
379	Adventist Medical Center	Portland	Oregon	United States	97216
380	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
381	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
382	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon	United States	97227
383	Northwest Cancer Specialists at Rose Quarter Cancer Center	Portland	Oregon	United States	97227
384	Salem Hospital Regional Cancer Care Services	Salem	Oregon	United States	97309-5014
385	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
386	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
387	St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	Pennsylvania	United States	18015
388	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
389	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
390	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania	United States	18201
391	Penn State Children's Hospital	Hershey	Pennsylvania	United States	17033-0850
392	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
393	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17604
394	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
395	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283
396	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
397	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134-1095
398	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
399	UPMC Cancer Centers	Pittsburgh	Pennsylvania	United States	15232
400	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
401	Guthrie Cancer Center at Guthrie Clinic Sayre	Sayre	Pennsylvania	United States	18840
402	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania	United States	18501
403	Hematology and Oncology Associates of Northeastern Pennsylvania	Scranton	Pennsylvania	United States	18510
404	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
405	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
406	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
407	Susquehanna Cancer Center at Divine Providence Hospital	Williamsport	Pennsylvania	United States	17701
408	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania	United States	17405
409	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
410	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
411	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
412	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
413	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee	United States	37662
414	East Tennessee Children's Hospital	Knoxville	Tennessee	United States	37901
415	Center for Biomedical Research	Knoxville	Tennessee	United States	37909
416	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838
417	Harrington Cancer Center	Amarillo	Texas	United States	79106
418	Medical City Dallas Hospital	Dallas	Texas	United States	75230
419	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78207
420	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229-3993
421	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
422	American Fork Hospital	American Fork	Utah	United States	84003
423	Sandra L. Maxwell Cancer Center	Cedar City	Utah	United States	84720
424	Logan Regional Hospital	Logan	Utah	United States	84321
425	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
426	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah	United States	84403
427	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
428	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
429	LDS Hospital	Salt Lake City	Utah	United States	84103
430	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah	United States	84106
431	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84112
432	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
433	Danville Regional Medical Center	Danville	Virginia	United States	24541
434	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
435	Southwest Virginia Regional Cancer Center at Wellmonth Health	Norton	Virginia	United States	24273
436	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
437	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
438	Providence Centralia Hospital	Centralia	Washington	United States	98531-9027
439	St. Francis Hospital	Federal Way	Washington	United States	98003
440	Columbia Basin Hematology	Kennewick	Washington	United States	99336
441	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington	United States	98273
442	Providence St. Peter Hospital Regional Cancer Center	Olympia	Washington	United States	98506-5166
443	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington	United States	98370
444	Good Samaritan Cancer Center	Puyallup	Washington	United States	98372
445	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
446	Group Health Central Hospital	Seattle	Washington	United States	98112
447	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
448	Polyclinic First Hill	Seattle	Washington	United States	98122
449	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195
450	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
451	Evergreen Hematology and Oncology, PS	Spokane	Washington	United States	99218
452	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington	United States	98405-3004
453	Allenmore Hospital	Tacoma	Washington	United States	98405
454	CCOP - Northwest	Tacoma	Washington	United States	98405
455	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington	United States	98405
456	St. Clare Hospital	Tacoma	Washington	United States	98499
457	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
458	Legacy Salmon Creek Medical Center	Vancouver	Washington	United States	98686
459	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028
460	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
461	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia	United States	25302
462	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia	United States	25701
463	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia	United States	26506
464	Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital	Parkersburg	West Virginia	United States	26102
465	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia	United States	26003
466	Fox Valley Hematology and Oncology - East Grant Street	Appleton	Wisconsin	United States	54911-3496
467	Aurora Memorial Hospital of Burlington	Burlington	Wisconsin	United States	53105
468	Marshfield Clinic - Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
469	Center for Cancer Treatment & Prevention at Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
470	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin	United States	54701
471	Vince Lombardi Cancer Center at Aurora Lakeland Medical Center - Elkhorn	Elkhorn	Wisconsin	United States	53121
472	Oncology Alliance - Franklin	Franklin	Wisconsin	United States	53132
473	Oncology Alliance, SC - Milwaukee - East	Glendale	Wisconsin	United States	53212-1038
474	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
475	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
476	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
477	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
478	Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
479	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin	United States	53038
480	Oncology Alliance - Kenosha South	Kenosha	Wisconsin	United States	53143
481	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601
482	Dean Medical Center - Madison	Madison	Wisconsin	United States	53717
483	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
484	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
485	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
486	Vince Lombardi Cancer Clinic - Marinette	Marinette	Wisconsin	United States	54143
487	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
488	Saint Joseph's Hospital	Marshfield	Wisconsin	United States	54449
489	Aurora Advanced Healthcare East Mequon Clinic	Mequon	Wisconsin	United States	53092
490	Medical Consultants, Limited	Milwaukee	Wisconsin	United States	53215
491	Oncology Alliance, SC - Milwaukee - South	Milwaukee	Wisconsin	United States	53215
492	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
493	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin	United States	54548
494	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
495	Aurora Health Center - Racine	Racine	Wisconsin	United States	53406-5661
496	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
497	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin	United States	54868
498	Vince Lombardi Cancer Clinic - Sheboygan	Sheboygan	Wisconsin	United States	53081
499	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
500	Saint Michael's Hospital Cancer Center	Stevens Point	Wisconsin	United States	54481
501	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
502	Aurora Medical Center	Summit	Wisconsin	United States	53066
503	Vince Lombardi Cancer Clinic - Two Rivers	Two Rivers	Wisconsin	United States	54241
504	Aurora Health Center - Waukesha	Waukesha	Wisconsin	United States	53188
505	Marshfield Clinic - Wausau Center	Wausau	Wisconsin	United States	54401
506	Oncology Alliance, SC - Milwaukee - West	Wauwatosa	Wisconsin	United States	53226
507	Diagnostic and Treatment Center	Weston	Wisconsin	United States	54476
508	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
509	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
510	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
511	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801
512	Westmead Institute for Cancer Research at Westmead Hospital	Westmead	New South Wales	Australia	2145
513	Cross Cancer Institute at University of Alberta	Edmonton	Alberta	Canada	T6G 1Z2
514	British Columbia Cancer Agency - Centre for the Southern Interior	Kelowna	British Columbia	Canada	V1Y 5L3
515	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia	Canada	V3V 1Z2
516	British Columbia Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
517	British Columbia Cancer Agency - Vancouver Island Centre	Victoria	British Columbia	Canada	V8R 6V5
518	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
519	Nova Scotia Cancer Centre	Halifax	Nova Scotia	Canada	B3H 1V7
520	Royal Victoria Hospital of Barrie	Barrie	Ontario	Canada	L4M 6M2
521	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
522	London Regional Cancer Program at London Health Sciences Centre	London	Ontario	Canada	N6A 4L6
523	R. S. McLaughlin Durham Regional Cancer Centre at Lakeridge Health Oshawa	Oshawa	Ontario	Canada	L1G 2B9
524	St. Catharines General Hospital at Niagara Health System	St. Catharines	Ontario	Canada	L2R 7C6
525	Edmond Odette Cancer Centre at Sunnybrook	Toronto	Ontario	Canada	M4N 3M5
526	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
527	Trillium Health Centre - Mississauga Site	Toronto	Ontario	Canada	M9C 1A5
528	Windsor Regional Cancer Centre at Windsor Regional Hospital	Windsor	Ontario	Canada	N8W 2X3
529	Hopital Notre-Dame du CHUM	Montreal	Quebec	Canada	H2L 4M1
530	McGill Cancer Centre at McGill University	Montreal	Quebec	Canada	H2W 1S6
531	CHUM - Hotel Dieu Hospital	Montreal	Quebec	Canada	H2W 1T8
532	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan	Canada	S4T 7T1
533	Pretoria Academic Hospital	Pretoria		South Africa	0002

Sponsors and Collaborators

• ECOG-ACRIN Cancer Research Group
• National Cancer Institute (NCI)
• Southwest Oncology Group
• Cancer and Leukemia Group B
• NCIC Clinical Trials Group
• Children's Oncology Group

Investigators

• Study Chair: Sanjiv S. Agarwala, MD, St. Luke's Cancer Network at St. Luke's Hospital
• Study Chair: John M. Kirkwood, MD, UPMC Cancer Center at UPMC Presbyterian
• Study Chair: Lawrence E. Flaherty, MD, Barbara Ann Karmanos Cancer Institute
• Study Chair: William E. Carson, MD, Ohio State University Comprehensive Cancer Center
• Study Chair: Michael Smylie, MD, MB, ChB, Cross Cancer Institute at University of Alberta
• Principal Investigator: Alberto S. Pappo, MD, Texas Children's Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ECOG-ACRIN Cancer Research Group
• ClinicalTrials.gov Identifier: NCT00003641
• Other Study ID Numbers: E1697; E1697; U10CA023318; CDR0000066727
• First Posted: Jan 27, 2003
• Last Update Posted: Jun 10, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by ECOG-ACRIN Cancer Research Group: stage II melanoma; stage III melanoma
• Additional relevant MeSH terms: Melanoma; Interferons; Interferon-alpha; Interferon alpha-2

Study Results

Participant Flow

Recruitment Details	The study was activated on December 22, 1998, and closed to accrual on October 26, 2010 with final accrual of 1150 patients

Arm/Group Title	Observation	Interferon Alfa-2b
Arm/Group Description	Patients undergo observation for 4 weeks.	Patients receive high-dose interferon alfa-2b IV over 20 minutes daily for 5 consecutive days. Treatment repeats weekly for 4 weeks in the absence of unacceptable toxicity. interferon alfa-2b: Given IV
Period Title: Overall Study
STARTED	569	581
Treated	2	569
Toxicity Assessed	439	568
COMPLETED	0	407
NOT COMPLETED	569	174

Baseline Characteristics

Arm/Group Title	Observation	Interferon Alfa-2b	Total
Arm/Group Description	Patients undergo observation for 4 weeks.	Patients receive high-dose interferon alfa-2b IV over 20 minutes daily for 5 consecutive days. Treatment repeats weekly for 4 weeks in the absence of unacceptable toxicity. interferon alfa-2b: Given IV	Total of all reporting groups
Overall Participants	569	581	1150
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52	52	52
Sex/Gender, Customized (participants) [Number]
Female	248 43.6%	244 42%	492 42.8%
Male	320 56.2%	336 57.8%	656 57%
Missing	1 0.2%	1 0.2%	2 0.2%

Outcome Measures

1. Primary Outcome

Title	5-year Relapse-free Survival Rate
Description	Relapse-free survival (RFS) was defined as time from randomization to disease relapse or death from any cause, whichever occurred first. Patients without disease relapse were censored at last disease assessment date known of free of relapse. Kaplan-Meier method was used to estimate 5-year RFS rate in the intent-to-treat (ITT) patients.
Time Frame	assessed every 3 months for 2 years, every 6 months for 3 years

Outcome Measure Data

Analysis Population Description

all randomized patients

Arm/Group Title	Observation	Interferon Alfa-2b
Arm/Group Description	Patients undergo observation for 4 weeks.	Patients receive high-dose interferon alfa-2b IV over 20 minutes daily for 5 consecutive days. Treatment repeats weekly for 4 weeks in the absence of unacceptable toxicity. interferon alfa-2b: Given IV
Measure Participants	569	581
Number (95% Confidence Interval) [proportion of participants]	0.70 0.1%	0.70 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Observation, Interferon Alfa-2b
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.964
	Comments
	Method	Log Rank
	Comments	stratified on the stratification factors used for randomization

2. Secondary Outcome

Title	5-year Overall Survival Rate
Description	Overall survival (OS) was defined as time from randomization to death from any cause. Patients still alive were censored at last known alive date. Kaplan-Meier method was used to estimate 5-year OS rate in the ITT patients.
Time Frame	assessed every 3 months for 2 years, every 6 months for 3 years

Outcome Measure Data

Analysis Population Description

all randomized patients

Arm/Group Title	Observation	Interferon Alfa-2b
Arm/Group Description	Patients undergo observation for 4 weeks.	Patients receive high-dose interferon alfa-2b IV over 20 minutes daily for 5 consecutive days. Treatment repeats weekly for 4 weeks in the absence of unacceptable toxicity. interferon alfa-2b: Given IV
Measure Participants	569	581
Number (95% Confidence Interval) [proportion of participants]	0.83 0.1%	0.83 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Observation, Interferon Alfa-2b
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.558
	Comments
	Method	Log Rank
	Comments	Stratified on the stratification factors used for randomization

Adverse Events

Time Frame	Assessed at the end of treatment (4 weeks) and for 30 days following the last dose of protocol drug, or until the initiation of subsequent treatment, whichever comes first
Adverse Event Reporting Description	Prior to diagnosis of relapse, any severe (Grade ≥ 3) long term toxicity that has not been previously reported was collected via the long-term follow up form, assessed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter until 15 years after randomization.These long term toxicities were included here as well.
Arm/Group Title	Observation		Interferon Alfa-2b
Arm/Group Description	Patients undergo observation for 4 weeks		Patients receive high-dose interferon alfa-2b IV over 20 minutes daily for 5 consecutive days
All Cause Mortality
	Observation		Interferon Alfa-2b
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Observation		Interferon Alfa-2b
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/439 (4.6%)		325/568 (57.2%)
Blood and lymphatic system disorders
Anemia	1/439 (0.2%)		0/568 (0%)
Hematologic-other	0/439 (0%)		1/568 (0.2%)
Cardiac disorders
Supraventricular arrhythmias	0/439 (0%)		1/568 (0.2%)
Cardiac-ischemia	0/439 (0%)		2/568 (0.4%)
Cardiac-left ventric	0/439 (0%)		1/568 (0.2%)
Myocarditis	0/439 (0%)		1/568 (0.2%)
Ear and labyrinth disorders
INNER EAR/HEARING	2/439 (0.5%)		0/568 (0%)
Gastrointestinal disorders
Constipation	0/439 (0%)		4/568 (0.7%)
Nausea	0/439 (0%)		28/568 (4.9%)
STOMATITIS	0/439 (0%)		1/568 (0.2%)
Vomiting	0/439 (0%)		19/568 (3.3%)
GI-other	0/439 (0%)		2/568 (0.4%)
Abdominal pain	0/439 (0%)		2/568 (0.4%)
General disorders
Fatigue	0/439 (0%)		70/568 (12.3%)
Fever	0/439 (0%)		4/568 (0.7%)
Rigors/chills	0/439 (0%)		1/568 (0.2%)
CONSTITUTIONAL	0/439 (0%)		1/568 (0.2%)
Chest pain	0/439 (0%)		1/568 (0.2%)
Pain-other	0/439 (0%)		1/568 (0.2%)
Immune system disorders
Allergic reaction	0/439 (0%)		1/568 (0.2%)
Infections and infestations
Catheter-related infection	0/439 (0%)		1/568 (0.2%)
Infection w/ grade 3 or 4 neutropenia	0/439 (0%)		2/568 (0.4%)
INFECTION W/ UNKNOWN ANC	0/439 (0%)		2/568 (0.4%)
Infection w/o neutropenia	0/439 (0%)		2/568 (0.4%)
INFECTION-OTHER	0/439 (0%)		2/568 (0.4%)
Investigations
Leukocytes decreased	0/439 (0%)		38/568 (6.7%)
Neutrophils decreased	8/439 (1.8%)		130/568 (22.9%)
Platelets decreased	0/439 (0%)		3/568 (0.5%)
Alkaline phosphatase increased	2/439 (0.5%)		2/568 (0.4%)
Blood bilirubin increased	1/439 (0.2%)		4/568 (0.7%)
GGT increased	0/439 (0%)		2/568 (0.4%)
Aspartate aminotransferase increased	1/439 (0.2%)		74/568 (13%)
Alanine aminotransferase increased	0/439 (0%)		30/568 (5.3%)
Creatinine increased	6/439 (1.4%)		13/568 (2.3%)
Metabolism and nutrition disorders
Anorexia	0/439 (0%)		11/568 (1.9%)
Dehydration	0/439 (0%)		1/568 (0.2%)
HYPERGLYCEMIA	0/439 (0%)		1/568 (0.2%)
HYPERTRIGLYCERIDEMIA	0/439 (0%)		1/568 (0.2%)
HYPOCALCEMIA	0/439 (0%)		1/568 (0.2%)
HYPOKALEMIA	0/439 (0%)		1/568 (0.2%)
HYPONATREMIA	0/439 (0%)		1/568 (0.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/439 (0%)		7/568 (1.2%)
Bone pain	0/439 (0%)		2/568 (0.4%)
Myalgia	0/439 (0%)		13/568 (2.3%)
Nervous system disorders
Vasovagal episode	0/439 (0%)		1/568 (0.2%)
Ataxia	0/439 (0%)		1/568 (0.2%)
Depressed level of consciousness	0/439 (0%)		3/568 (0.5%)
Dizziness/lightheadedness	0/439 (0%)		3/568 (0.5%)
Memory loss	0/439 (0%)		1/568 (0.2%)
Neuropathy-cranial	0/439 (0%)		1/568 (0.2%)
Neuropathy-motor	0/439 (0%)		3/568 (0.5%)
Seizure	0/439 (0%)		1/568 (0.2%)
Speech impairment	0/439 (0%)		2/568 (0.4%)
Syncope	1/439 (0.2%)		3/568 (0.5%)
VERTIGO	0/439 (0%)		1/568 (0.2%)
Neurologic-other	0/439 (0%)		1/568 (0.2%)
Headache	0/439 (0%)		42/568 (7.4%)
Psychiatric disorders
Confusion	0/439 (0%)		4/568 (0.7%)
Insomnia	0/439 (0%)		5/568 (0.9%)
Anxiety/agitation	0/439 (0%)		6/568 (1.1%)
Depression	0/439 (0%)		11/568 (1.9%)
Renal and urinary disorders
Hematuria	0/439 (0%)		1/568 (0.2%)
URINARY FREQUENCY/URGENCY	0/439 (0%)		1/568 (0.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/439 (0%)		2/568 (0.4%)
HYPOXIA	0/439 (0%)		1/568 (0.2%)
PLEURAL EFFUSION	0/439 (0%)		1/568 (0.2%)
Pneumonitis/pulmonary infiltrates	0/439 (0%)		1/568 (0.2%)
Skin and subcutaneous tissue disorders
Rash/desquamation	0/439 (0%)		5/568 (0.9%)
Vascular disorders
Hypertension	2/439 (0.5%)		5/568 (0.9%)
Hypotension	0/439 (0%)		1/568 (0.2%)
Thrombosis/embolism	0/439 (0%)		1/568 (0.2%)
Other (Not Including Serious) Adverse Events
	Observation		Interferon Alfa-2b
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	74/439 (16.9%)		558/568 (98.2%)
Blood and lymphatic system disorders
Anemia	12/439 (2.7%)		123/568 (21.7%)
Gastrointestinal disorders
Constipation	2/439 (0.5%)		106/568 (18.7%)
Nausea	1/439 (0.2%)		340/568 (59.9%)
Vomiting	0/439 (0%)		133/568 (23.4%)
GI-other	0/439 (0%)		41/568 (7.2%)
General disorders
Fatigue	11/439 (2.5%)		454/568 (79.9%)
Fever	0/439 (0%)		256/568 (45.1%)
Rigors/chills	0/439 (0%)		342/568 (60.2%)
Pain-other	17/439 (3.9%)		33/568 (5.8%)
Investigations
Leukocytes decreased	6/439 (1.4%)		321/568 (56.5%)
Neutrophils decreased	4/439 (0.9%)		283/568 (49.8%)
Platelets decreased	2/439 (0.5%)		200/568 (35.2%)
Weight loss	0/439 (0%)		120/568 (21.1%)
Alkaline phosphatase increased	2/439 (0.5%)		69/568 (12.1%)
Blood bilirubin increased	2/439 (0.5%)		43/568 (7.6%)
Aspartate aminotransferase increased	8/439 (1.8%)		373/568 (65.7%)
Alanine aminotransferase increased	4/439 (0.9%)		80/568 (14.1%)
Metabolism and nutrition disorders
Anorexia	0/439 (0%)		283/568 (49.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/439 (0.9%)		137/568 (24.1%)
Myalgia	3/439 (0.7%)		229/568 (40.3%)
Nervous system disorders
Taste disturbance	0/439 (0%)		176/568 (31%)
Dizziness/lightheadedness	0/439 (0%)		95/568 (16.7%)
Neuropathy-sensory	8/439 (1.8%)		41/568 (7.2%)
Headache	8/439 (1.8%)		270/568 (47.5%)
Psychiatric disorders
Insomnia	3/439 (0.7%)		113/568 (19.9%)
Anxiety/agitation	7/439 (1.6%)		91/568 (16%)
Depression	4/439 (0.9%)		90/568 (15.8%)
Skin and subcutaneous tissue disorders
Sweating	0/439 (0%)		83/568 (14.6%)
Alopecia	1/439 (0.2%)		30/568 (5.3%)
Rash/desquamation	3/439 (0.7%)		64/568 (11.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.