S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00006237
• Collaborator: National Cancer Institute (NCI) (NIH), Eastern Cooperative Oncology Group (Other), Cancer and Leukemia Group B (Other), Children's Oncology Group (Other)
• Enrollment: 432
• Locations: 297
• Arms: 2
• Duration (Months): 143
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Interferon alfa may interfere with the growth of cancer cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known whether interferon alfa is more effective with or without combination chemotherapy and interleukin-2 for melanoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of interferon alfa with or without combination chemotherapy consisting of cisplatin, vinblastine, and dacarbazine, plus interleukin-2, in treating patients who have melanoma.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: interleukin-2; Biological: filgrastim; Biological: interferon alfa; Drug: cisplatin; Drug: dacarbazine; Drug: vinblastine	Phase 3

Detailed Description

OBJECTIVES:

• Compare the overall survival and disease-free survival of patients with high-risk melanoma treated with interferon alfa vs cisplatin, vinblastine, and dacarbazine plus interferon alfa and interleukin-2.

• Compare the toxic effects of these treatment regimens in these patients.

• Determine the relationship between minimal residual disease (MRD) status at 12 weeks and 52 weeks and overall survival of patients treated with these regimens.

• Compare the effects of these treatment regimens on the MRD status of these patients.

• Determine the relationship between clinical characteristics (number of involved lymph nodes, ulcerated primary, and extracapsular extension) and MRD in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to nodal status (N1 or N2 vs N3), degree of lymph node involvement (micrometastases only vs any macrometastases, including satellite/in-transit metastases), and ulceration of the primary tumor (yes vs no vs unknown primary). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive interferon alfa IV on days 1-5 of weeks 1-4 followed by interferon alfa subcutaneously (SC) on days 1, 3, and 5 of weeks 5-52 in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive cisplatin IV over 30 minutes followed by vinblastine IV on days 1-4. Patients also receive dacarbazine IV over 1 hour on day 1, interleukin-2 IV over 96 hours on days 1-4, and interferon alfa SC on days 1-5, 8, 10, and 12. In addition, patients receive filgrastim (G-CSF) SC on days 6-15. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 410 patients (205 per treatment arm) will be accrued for this study within 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 432 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Trial of High Dose Interferon Alfa 2-b Versus Cisplatin, Vinblastine, DTIC Plus IL-2 and Interferon in Patients With High Risk Melanoma
• Study Start Date: Aug 1, 2000
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I Patients receive interferon alfa IV on days 1-5 of weeks 1-4 followed by interferon alfa subcutaneously (SC) on days 1, 3, and 5 of weeks 5-52 in the absence of disease progression or unacceptable toxicity.	Biological: interferon alfa; Given IV and subcutaneously
Experimental: Arm II Patients receive cisplatin IV over 30 minutes followed by vinblastine IV on days 1-4. Patients also receive dacarbazine IV over 1 hour on day 1, interleukin-2 IV over 96 hours on days 1-4, and interferon alfa SC on days 1-5, 8, 10, and 12. In addition, patients receive filgrastim (G-CSF) SC on days 6-15. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.	Biological: interleukin-2; Given IV; Other Names: aldesleukin ; Biological: filgrastim; Given subcutaneously; Biological: interferon alfa; Given IV and subcutaneously; Drug: cisplatin; Given IV; Drug: dacarbazine; Given IV; Drug: vinblastine; Given IV

Outcome Measures

Primary Outcome Measures

1. 5-year Overall Survival [Every three months for a year, every six months for years 2-5, annual for years 5-10]

   Overall survival was measured from the date of registration to study until death from any cause with observations censored at the date of last contact for patients last known to be alive.

2. 5-year Relapse-Free Survival [Every three months for the first year, every 6 months for years 2-5, annually for years 6-10]

   Measured from date of registration to date of first observation of progressive disease or death due to any cause.

Secondary Outcome Measures

1. Toxicity [While on treatment, patients on the HDIFN arm were assessed weekly for the 1st month, then every 2 weeks for the 2nd month, then every 3 months therafter; patients on the biochemo arm were assessed daily for the 1st 5 days, then weekly thereafter.]

   Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically proven melanoma of cutaneous origin or from unknown primary at initial presentation of primary or first clinically detected nodal or satellite/in-transit recurrence

• No distant metastases

• No melanoma of ocular, mucosal, or other non-cutaneous origin

• One of the following criteria must apply for patients with newly diagnosed melanoma OR a previously diagnosed primary with current subsequent, clinical, regional nodal disease and/or satellite/in-transit disease:

• Ulcerated primary melanoma with 1 or more involved lymph nodes (micro/occult or macro/clinically overt)

• Non-ulcerated or unknown primary melanoma with one macro/clinically overt lymph node metastasis, including a single matted nodal mass

• No non-ulcerated or unknown primary tumor and a single micrometastatic lymph node

• Non-ulcerated melanoma with two or more lymph node metastases (micro/occult or macro/clinically overt) and/or matted nodes

• Any satellite/in transit metastasis with or without lymph node involvement

• Patients with recurrent disease must have recurrent disease in the regional nodal basin of a prior complete lymphadenectomy

• Multiple regional nodal basin involvement allowed if they are appropriate anatomic drainage basins for primary site

• Patients must be disease free at time of enrollment based on the following surgical criteria:

• Patients at initial presentation of melanoma must undergo adequate wide excision of primary lesion

• Patients with previously diagnosed melanoma must have all disease resected with pathologically negative margins and no disease at primary site or second resection of primary

• Full lymphadenectomy required of all patients including those with positive sentinel nodes or positive satellite/in-transit metastasis

• No more than 56 days since prior lymphadenectomy OR surgery to remove recurrent disease after prior complete lymphadenectomy

• Must be willing to participate in minimal residual disease studies if registered on the study on 3/1/2003 or later

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)

• SGOT or SGPT no greater than 2 times ULN

• LDH and alkaline phosphatase no greater than 2 times ULN (above normal value requires a contrast-enhanced CT scan or MRI of liver)

• No known recent hepatitis positivity by PCR

Renal:

• Creatinine no greater than 1.5 mg/dL OR

• Creatinine clearance at least 75 mL/min

Cardiovascular:

• No congestive heart failure

• No coronary artery disease

• No serious cardiac arrhythmia

• No prior myocardial infarction

• Normal cardiac stress test required if any of the following are present:

• Over age 50

• Abnormal EKG

• History of cardiac disease

Pulmonary:

• No symptomatic pulmonary disease

Other:

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No autoimmune disorders or conditions of immunosuppression

• No other prior malignancy within the past 5 years except the following:

• Adequately treated basal cell or squamous cell skin cancer

• Carcinoma in situ of the cervix

• Adequately treated stage I or II cancer in remission

• HIV negative

• No known AIDS or HIV-1 associated complex

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior immunotherapy, including interferon, interleukin, levamisole, or other biologic response modifiers

• No other concurrent biologic therapy

Chemotherapy:

• No prior chemotherapy (including infusion or perfusion therapy)

• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent systemic corticosteroids or topical steroid creams

• Concurrent steroid antihistamines allowed if no alternative

• No concurrent hormonal therapy

Radiotherapy:

• No prior radiotherapy

• Prior postlumpectomy radiotherapy for breast cancer allowed

• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

• No concurrent surgery

Other:

• No concurrent anti-hypertensive medications (arm II only)

• No concurrent immunosuppressive agents

• No other concurrent anticancer therapy

• Antihistamines allowed if no alternative medication suitable

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama	United States	35294
2	Mobile Infirmary Medical Center	Mobile	Alabama	United States	36652-2144
3	Banner Thunderbird Medical Center	Glendale	Arizona	United States	85306
4	Banner Good Samaritan Medical Center	Phoenix	Arizona	United States	85006
5	CCOP - Western Regional, Arizona	Phoenix	Arizona	United States	85006
6	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016-7710
7	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724-5024
8	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center	Ft. Smith	Arkansas	United States	72903
9	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
10	Eden Medical Center	Castro Valley	California	United States	94546
11	Saint Rose Hospital	Hayward	California	United States	94545
12	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
13	Highland General Hospital	Oakland	California	United States	94602
14	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
15	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609
16	Valley Care Medical Center	Pleasanton	California	United States	94588
17	Kaiser Permanente Medical Center - Oakland	Sacramento	California	United States	95825
18	Scripps Cancer Center - San Diego	San Diego	California	United States	92121
19	Veterans Affairs Medical Center - San Diego	San Diego	California	United States	92161
20	Doctors Medical Center - San Pablo Campus	San Pablo	California	United States	94806
21	CCOP - Santa Rosa Memorial Hospital	Sana Rosa	California	United States	95405
22	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
23	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
24	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut	United States	06360-2875
25	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut	United States	06050
26	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
27	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
28	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
29	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
30	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida	United States	32207
31	All Children's Hospital	St. Petersburg	Florida	United States	33701
32	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida	United States	33607
33	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida	United States	33407
34	Winship Cancer Institute of Emory University	Altanta	Georgia	United States	30322
35	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia	United States	30033
36	Pearlman Comprehensive Cancer Center at South Georgia Medical Center	Valdosta	Georgia	United States	31603
37	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho	United States	83712
38	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60507
39	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
40	Graham Hospital	Canton	Illinois	United States	61520
41	Memorial Hospital	Carthage	Illinois	United States	62321
42	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
43	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
44	University of Illinois Cancer Center	Chicago	Illinois	United States	60612-7243
45	Veterans Affairs Medical Center - Chicago Westside Hospital	Chicago	Illinois	United States	60612
46	Mercy Hospital and Medical Center	Chicago	Illinois	United States	60616
47	Swedish Covenant Hospital	Chicago	Illinois	United States	60625
48	Sherman Hospital	Elgin	Illinois	United States	60120
49	Eureka Community Hospital	Eureka	Illinois	United States	61530
50	Evanston Northwestern Healthcare - Evanston Hospital	Evanston	Illinois	United States	60201-1781
51	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
52	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
53	Mason District Hospital	Havana	Illinois	United States	62644
54	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
55	Midwest Center for Hematology/Oncology	Joliet	Illinois	United States	60432
56	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
57	Kewanee Hospital	Kewanee	Illinois	United States	61443
58	McDonough District Hospital	Macomb	Illinois	United States	61455
59	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
60	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois	United States	60714
61	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
62	Community Cancer Center	Normal	Illinois	United States	61761
63	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
64	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
65	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
66	Proctor Hospital	Peoria	Illinois	United States	61614
67	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
68	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
69	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
70	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
71	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
72	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
73	Perry Memorial Hospital	Princeton	Illinois	United States	61356
74	Swedish-American Regional Cancer Center	Rockford	Illinois	United States	61104-2315
75	Hematology Oncology Associates - Skokie	Skokie	Illinois	United States	60076
76	Hematology/Oncology of the North Shore at Gross Point Medical Center	Skokie	Illinois	United States	60076
77	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
78	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
79	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
80	Elkhart General Hospital	Elkhart	Indiana	United States	46515
81	Howard Community Hospital	Kokomo	Indiana	United States	46904
82	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
83	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
84	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
85	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
86	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
87	McFarland Clinic, PC	Ames	Iowa	United States	50010
88	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa	United States	52803
89	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
90	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
91	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
92	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
93	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
94	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
95	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
96	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1002
97	Veterans Affairs Medical Center - Kansas City	Kansas City	Kansas	United States	64128
98	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas	United States	67401
99	Cotton-O'Neil Cancer Center	Topeka	Kansas	United States	66606
100	St. Francis Comprehensive Cancer Center	Topeka	Kansas	United States	66606
101	Louisiana State University Health Sciences Center - Monroe	Monroe	Louisiana	United States	71210
102	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana	United States	71130-3932
103	Union Hospital Cancer Program at Union Hospital	Elkton MD	Maryland	United States	21921
104	Tufts-NEMC Cancer Center	Boston	Massachusetts	United States	02111
105	Boston University Cancer Research Center	Boston	Massachusetts	United States	02118
106	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
107	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
108	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
109	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
110	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
111	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
112	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
113	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
114	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
115	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
116	Hurley Medical Center	Flint	Michigan	United States	48503
117	Great Lakes Cancer Institute at McLaren Regional Medical Center	Flint	Michigan	United States	48532
118	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
119	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
120	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
121	Metro Health Hospital	Grand Rapids	Michigan	United States	49506
122	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
123	Holland Community Hospital	Holland	Michigan	United States	49423
124	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
125	Foote Memorial Hospital	Jackson	Michigan	United States	49201
126	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
127	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
128	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
129	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
130	Upper Michigan Cancer Center at Marquette General Hospital	Marquette	Michigan	United States	49855
131	Hackley Hospital	Muskegon	Michigan	United States	49442
132	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
133	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
134	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
135	Munson Medical Center	Traverse City	Michigan	United States	49684
136	St. John Macomb Hospital	Warren	Michigan	United States	48093
137	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
138	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
139	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
140	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
141	CCOP - Duluth	Duluth	Minnesota	United States	55805
142	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
143	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
144	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
145	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
146	Meeker County Memorial Hospital	Lichfield	Minnesota	United States	55355
147	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
148	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
149	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
150	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
151	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
152	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
153	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
154	HealthEast Cancer Care at St. Joseph's Hospital	St Paul	Minnesota	United States	55102
155	Park Nicollet Cancer Center	St. Louis Park	Minnesota	United States	55416
156	Regions Hospital Cancer Care Center	St. Paul	Minnesota	United States	55101
157	United Hospital	St. Paul	Minnesota	United States	55102
158	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
159	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota	United States	55125
160	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
161	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
162	CCOP - Kansas City	Kansas City	Missouri	United States	64131
163	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
164	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
165	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
166	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
167	Billings Clinic Cancer Center	Billings	Montana	United States	59107-5100
168	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
169	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
170	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
171	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
172	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
173	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
174		Great Falls	Montana	United States	59405
175	St. Peter's Hospital	Helena	Montana	United States	59601
176	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
177	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
178	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
179	Community Medical Center	Missoula	Montana	United States	59801
180	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
181	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
182	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
183	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska	United States	68848-1990
184	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
185	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
186	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
187	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey	United States	08053
188	Booker Cancer Center at Riverview Medical Center	Red Bank	New Jersey	United States	07701
189	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
190	Fox Chase Virtua Health Cancer Program at Virtua West Jersey	Voorhees	New Jersey	United States	08043
191	Lovelace Medical Center - Gibson	Albuquerque	New Mexico	United States	87108
192	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
193	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
194	Adirondack Cancer Care - Glens Falls	Glens Falls	New York	United States	12801
195	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
196	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
197	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
198	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
199	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
200	MeritCare Broadway	Fargo	North Dakota	United States	58122
201	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio	United States	44708
202	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
203	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
204	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio	United States	44109
205	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
206	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio	United States	43210-1240
207	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
208	CCOP - Columbus	Columbus	Ohio	United States	43215
209	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
210	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
211	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
212	Grady Memorial Hospital	Delaware	Ohio	United States	43015
213	Community Oncology Group at Cleveland Clinic Cancer Center	Independence	Ohio	United States	44131
214	Fairfield Medical Center	Lancaster	Ohio	United States	43130
215	St. Rita's Medical Center	Lima	Ohio	United States	45801
216	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
217	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
218	Mercy Medical Center	Springfield	Ohio	United States	45504
219	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
220	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
221	Cleveland Clinic - Wooster	Wooster	Ohio	United States	44691
222	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
223	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
224	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
225	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon	United States	97210
226	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
227	Adventist Medical Center	Portland	Oregon	United States	97216
228	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
229	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
230	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon	United States	97227
231	Salem Hospital Regional Cancer Care Services	Salem	Oregon	United States	97309-5014
232	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
233	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
234	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
235	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
236	Central Pennsylvania Hematology and Medical Oncology Associates, PC	Lemoyne	Pennsylvania	United States	17043
237	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
238	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134-1095
239	UPMC Cancer Centers	Pittsburgh	Pennsylvania	United States	15232
240	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
241	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
242	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
243	Roper St. Francis Cancer Center at Roper Hospital	Charleston	South Carolina	United States	29401
244	Palmetto Health South Carolina Cancer Center	Columbia	South Carolina	United States	29203
245	CCOP - Greenville	Greenville	South Carolina	United States	29615
246	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
247	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
248	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
249	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
250	University of Tennessee Cancer Institute - Memphis	Memphis	Tennessee	United States	38104
251	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838
252	Harrington Cancer Center	Amarillo	Texas	United States	79106
253	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234-6200
254	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104
255	Wilford Hall Medical Center	Lackland AFB	Texas	United States	78236
256	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78207
257	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
258	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84112
259	Primary Children's Medical Center	Salt Lake City	Utah	United States	84113-1100
260	Martha Jefferson Hospital Cancer Care Center	Charlottesville	Virginia	United States	22901
261	Auburn Regional Center for Cancer Care	Auburn	Washington	United States	98002
262	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
263	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
264	Providence Centralia Hospital	Centralia	Washington	United States	98531-9027
265	St. Francis Hospital	Federal Way	Washington	United States	98003
266	Skagit Valley Hospital Cancer Care Center	Mt. Vernon	Washington	United States	98273
267	Providence St. Peter Hospital Regional Cancer Center	Olympia	Washington	United States	98506-5166
268	Good Samaritan Cancer Center	Puyallup	Washington	United States	98372
269	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98104
270	Harborview Medical Center	Seattle	Washington	United States	98104
271	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
272	Group Health Central Hospital	Seattle	Washington	United States	98112
273	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
274	Polyclinic First Hill	Seattle	Washington	United States	98122
275	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195-6043
276	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
277	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington	United States	98405-3004
278	Allenmore Hospital	Tacoma	Washington	United States	98405
279	CCOP - Northwest	Tacoma	Washington	United States	98405
280	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington	United States	98405
281	St. Clare Hospital	Tacoma	Washington	United States	98499
282	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
283	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028
284	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia	United States	25304
285	Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital	Parkersburg	West Virginia	United States	26102
286	Fox Valley Hematology and Oncology - East Grant Street	Appleton	Wisconsin	United States	54911-3496
287	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
288	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
289	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
290	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
291	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
292	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
293	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
294	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
295	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
296	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801
297	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)
• Eastern Cooperative Oncology Group
• Cancer and Leukemia Group B
• Children's Oncology Group

Investigators

• Study Chair: Lawrence E. Flaherty, MD, Barbara Ann Karmanos Cancer Institute
• Principal Investigator: John A. Thompson, MD, Seattle Cancer Care Alliance
• Principal Investigator: John T. Vetto, MD, FACS, OHSU Knight Cancer Institute
• Study Chair: Michael B. Atkins, MD, Beth Israel Deaconess Medical Center
• Principal Investigator: John M. Kirkwood, MD, University of Pittsburgh
• Study Chair: Frank Haluska, MD, PhD, Massachusetts General Hospital
• Principal Investigator: Alberto S. Pappo, MD, Texas Children's Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00006237
• Other Study ID Numbers: S0008; U10CA032102; S0008; CALGB-500002; ECOG-S0008; COG-S0008; NCT00546416
• First Posted: Jan 27, 2003
• Last Update Posted: Mar 25, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by Southwest Oncology Group: stage III melanoma; recurrent melanoma
• Additional relevant MeSH terms: Melanoma; Interferons; Interferon-alpha; Aldesleukin; Interleukin-2; Dacarbazine; Vinblastine

Study Results

Participant Flow

Arm/Group Title	Interferon	Biochemotherapy
Arm/Group Description	interferon alfa IV	cisplatin, dacarbazine, interleukin-2, interferon alfa SC, filgrastim
Period Title: Overall Study
STARTED	212	220
Eligible	203	200
Eligible and Treated	203	199
COMPLETED	87	159
NOT COMPLETED	125	61

Baseline Characteristics

Arm/Group Title	Interferon	Biochemotherapy	Total
Arm/Group Description	interferon alfa	cisplatin, dacarbazine, interleukin-2, interferon alfa SC, filgrastim	Total of all reporting groups
Overall Participants	203	199	402
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	47	46	47
Sex: Female, Male (Count of Participants)
Female	62 30.5%	58 29.1%	120 29.9%
Male	141 69.5%	141 70.9%	282 70.1%
Region of Enrollment (participants) [Number]
United States	203 100%	199 100%	402 100%

Outcome Measures

1. Primary Outcome

Title	5-year Overall Survival
Description	Overall survival was measured from the date of registration to study until death from any cause with observations censored at the date of last contact for patients last known to be alive.
Time Frame	Every three months for a year, every six months for years 2-5, annual for years 5-10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Interferon	Biochemotherapy
Arm/Group Description	interferon alfa IV on days 1-5 of weeks 1-4 followed by interferon alfa subcutaneously (SC) on days 1, 3, and 5 of weeks 5-52 in the absence of disease progression or unacceptable toxicity.	cisplatin, dacarbazine, interleukin-2, interferon alfa SC, filgrastim
Measure Participants	203	199
Number [Percent of population]	56	56

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Interferon, Biochemotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	Log Rank
	Comments

2. Primary Outcome

Title	5-year Relapse-Free Survival
Description	Measured from date of registration to date of first observation of progressive disease or death due to any cause.
Time Frame	Every three months for the first year, every 6 months for years 2-5, annually for years 6-10

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Interferon	Biochemotherapy
Arm/Group Description	interferon alfa	cisplatin, dacarbazine, interleukin-2, interferon alfa SC, filgrastim
Measure Participants	203	199
Number [Percentage of population]	47	38

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Interferon, Biochemotherapy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Toxicity
Description	Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event
Time Frame	While on treatment, patients on the HDIFN arm were assessed weekly for the 1st month, then every 2 weeks for the 2nd month, then every 3 months therafter; patients on the biochemo arm were assessed daily for the 1st 5 days, then weekly thereafter.

Outcome Measure Data

Analysis Population Description

Eligible patients who started therapy

Arm/Group Title	Interferon	Biochemotherapy
Arm/Group Description	Interferon	Biochemotherapy
Measure Participants	193	185
Abdominal pain/cramping	1 0.5%	1 0.5%
Acidosis	0 0%	1 0.5%
Acute vascular leak syndrome	0 0%	1 0.5%
Alkaline phosphatase increase	0 0%	3 1.5%
Allergic reaction	1 0.5%	0 0%
Anal incontinence	0 0%	1 0.5%
Anemia	0 0%	8 4%
Anorexia	1 0.5%	9 4.5%
Anxiety/agitation	4 2%	5 2.5%
Apnea	1 0.5%	0 0%
Arrhythmia, NOS	2 1%	0 0%
Arthralgia	4 2%	3 1.5%
Bilirubin increase	0 0%	1 0.5%
Bone pain	0 0%	4 2%
CPK increase	0 0%	1 0.5%
Cardiovascular-other	1 0.5%	0 0%
Catheter related infection	0 0%	2 1%
Cerebrovascular ischemia	1 0.5%	0 0%
Colitis	0 0%	2 1%
Confusion	2 1%	3 1.5%
Constipation/bowel obstruction	0 0%	4 2%
Cranial neuropathy	1 0.5%	0 0%
Creatinine increase	0 0%	4 2%
Dehydration	1 0.5%	7 3.5%
Delusions	0 0%	1 0.5%
Depression	14 6.9%	4 2%
Diarrhea without colostomy	2 1%	6 3%
Dizziness/light headedness	2 1%	1 0.5%
Dizziness/vertigo, NOS	0 0%	1 0.5%
Double vision	0 0%	1 0.5%
Dyspnea	1 0.5%	2 1%
Eryth/rash/eruption/desq, NOS	1 0.5%	3 1.5%
Esophagitis/dysphagia	0 0%	2 1%
Eye-other	1 0.5%	0 0%
Fatigue/malaise/lethargy	38 18.7%	22 11.1%
Febrile neutropenia	1 0.5%	9 4.5%
Fever without neutropenia	1 0.5%	5 2.5%
Fever, NOS	0 0%	1 0.5%
Hallucinations	1 0.5%	1 0.5%
Headache	9 4.4%	5 2.5%
Hemorrhage w/ 3-4 thrombocyt	0 0%	1 0.5%
Hyperglycemia	2 1%	3 1.5%
Hyperkalemia	0 0%	1 0.5%
Hypermagnesemia	1 0.5%	1 0.5%
Hypertension	0 0%	1 0.5%
Hypertriglyceridemia	1 0.5%	0 0%
Hypocalcemia	0 0%	18 9%
Hypokalemia	1 0.5%	7 3.5%
Hypomagnesemia	0 0%	5 2.5%
Hyponatremia	0 0%	6 3%
Hypophosphatemia	0 0%	4 2%
Hypotension	0 0%	16 8%
Hypoxia	0 0%	1 0.5%
Infection w/o 3-4 neutropenia	0 0%	3 1.5%
Infection with 3-4 neutropenia	0 0%	9 4.5%
Infection, unk ANC	1 0.5%	2 1%
Insomnia	1 0.5%	1 0.5%
Leukopenia	12 5.9%	38 19.1%
Lipase increase	1 0.5%	2 1%
Local injection site reaction	1 0.5%	0 0%
Lymphopenia	0 0%	2 1%
Mood/consciousness change, NOS	0 0%	1 0.5%
Muscle weakness (not neuro)	0 0%	1 0.5%
Myalgia	7 3.4%	4 2%
Nausea	10 4.9%	51 25.6%
Neutropenia/granulocytopenia	25 12.3%	61 30.7%
PRBC transfusion	0 0%	3 1.5%
Pancreatitis	0 0%	1 0.5%
Personality/behavioral change	1 0.5%	0 0%
Petechiae/purpura	0 0%	1 0.5%
Platelet transfusion	0 0%	5 2.5%
Pruritus	1 0.5%	3 1.5%
Rash/desquamation	4 2%	10 5%
Renal failure	0 0%	1 0.5%
Reportable adverse event, NOS	1 0.5%	1 0.5%
Respiratory infect w/ neutrop	0 0%	2 1%
Rigors/chills	2 1%	1 0.5%
SGOT (AST) increase	18 8.9%	7 3.5%
SGPT (ALT) increase	32 15.8%	8 4%
Seizures	0 0%	2 1%
Sensory neuropathy	0 0%	2 1%
Stomatitis/pharyngitis	0 0%	1 0.5%
Surgery-wound infection	3 1.5%	0 0%
Syncope	2 1%	0 0%
Thrombocytopenia	1 0.5%	50 25.1%
Thrombosis/embolism	1 0.5%	1 0.5%
Typhlitis	0 0%	1 0.5%
Vertigo	1 0.5%	0 0%
Vomiting	9 4.4%	37 18.6%
Weakness (motor neuropathy)	1 0.5%	2 1%
Weight loss	3 1.5%	0 0%

Adverse Events

Time Frame	While the patient is on treatment until resolution of acute toxicities with maximum grade reported
Adverse Event Reporting Description	Regular investigator assessments are reported after each cycle of protocol treatment
Arm/Group Title	Interferon		Biochemotherapy
Arm/Group Description	interferon alfa		cisplatin, dacarbazine, interleukin-2, interferon alfa SC, filgrastim
All Cause Mortality
	Interferon		Biochemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Interferon		Biochemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/193 (1%)		4/185 (2.2%)
Blood and lymphatic system disorders
Platelet transfusion	0/193 (0%)		1/185 (0.5%)
Gastrointestinal disorders
Colitis	0/193 (0%)		1/185 (0.5%)
General disorders
Reportable adverse event, NOS	1/193 (0.5%)		0/185 (0%)
Infections and infestations
Respiratory infect w/ neutrop	0/193 (0%)		1/185 (0.5%)
Nervous system disorders
Cerebrovascular ischemia	1/193 (0.5%)		0/185 (0%)
Psychiatric disorders
Depression	0/193 (0%)		1/185 (0.5%)
Other (Not Including Serious) Adverse Events
	Interferon		Biochemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	132/193 (68.4%)		144/185 (77.8%)
Blood and lymphatic system disorders
Anemia	15/193 (7.8%)		27/185 (14.6%)
Gastrointestinal disorders
Diarrhea without colostomy	13/193 (6.7%)		0/185 (0%)
Nausea	37/193 (19.2%)		67/185 (36.2%)
Vomiting	23/193 (11.9%)		52/185 (28.1%)
General disorders
Fatigue/malaise/lethargy	79/193 (40.9%)		27/185 (14.6%)
Fever without neutropenia	23/193 (11.9%)		24/185 (13%)
Rigors/chills	27/193 (14%)		0/185 (0%)
Investigations
Alkaline phosphatase increase	0/193 (0%)		16/185 (8.6%)
Creatinine increase	0/193 (0%)		13/185 (7%)
Leukopenia	30/193 (15.5%)		42/185 (22.7%)
Neutropenia/granulocytopenia	38/193 (19.7%)		65/185 (35.1%)
SGOT (AST) increase	42/193 (21.8%)		20/185 (10.8%)
SGPT (ALT) increase	53/193 (27.5%)		20/185 (10.8%)
Thrombocytopenia	15/193 (7.8%)		58/185 (31.4%)
Weight loss	12/193 (6.2%)		0/185 (0%)
Metabolism and nutrition disorders
Anorexia	0/193 (0%)		11/185 (5.9%)
Hypocalcemia	0/193 (0%)		35/185 (18.9%)
Hypomagnesemia	0/193 (0%)		18/185 (9.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	12/193 (6.2%)		0/185 (0%)
Myalgia	23/193 (11.9%)		14/185 (7.6%)
Nervous system disorders
Headache	17/193 (8.8%)		0/185 (0%)
Psychiatric disorders
Anxiety/agitation	12/193 (6.2%)		10/185 (5.4%)
Depression	31/193 (16.1%)		0/185 (0%)
Skin and subcutaneous tissue disorders
Rash/desquamation	0/193 (0%)		11/185 (5.9%)
Vascular disorders
Hypotension	0/193 (0%)		22/185 (11.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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