S0001 RT and Carmustine With or Without O6BG in Patients With New Glioblastoma Multiforme or Gliosarcoma

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00017147
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 183
• Locations: 163
• Arms: 2
• Duration (Months): 134
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. O6-benzylguanine may help carmustine kill more tumor cells by making tumor cells more sensitive to the drug. It is not yet known whether radiation therapy and carmustine are more effective with or without O6-benzylguanine.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy plus carmustine with or without O6-benzylguanine in treating patients who have newly diagnosed glioblastoma multiforme or gliosarcoma.

Condition or Disease	Intervention/Treatment	Phase
Malignant Neoplasms of Eye, Brain and Other Parts of Central Nervous System	Drug: carmustine; Radiation: radiation therapy; Drug: O6-Benzylguanine	Phase 3

Detailed Description

OBJECTIVES:

• Compare the overall survival, failure-free survival, and progression-free survival of patients with newly diagnosed glioblastoma multiforme or gliosarcoma treated with radiotherapy and carmustine with or without O6-benzylguanine.

• Compare the frequency and severity of toxic effects of these regimens in these patients.

• Correlate the survival of these patients with the expression of O6-alkylguanine-DNA alkyltransferase.

OUTLINE: This is a randomized study. Patients are stratified according to age (under 50 vs 50 and over), prior surgery (biopsy only vs resection), and Zubrod performance status (0-1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy daily 5 days a week over 7 weeks for a total of 34 fractions. Patients also receive chemotherapy comprising O6-benzylguanine IV over 1 hour followed 6 hours later by carmustine IV over 1 hour on day 1 of radiotherapy. Chemotherapy repeats every 6 weeks for a maximum of 7 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients undergo radiotherapy as in arm I. Patients receive carmustine IV as in arm I.

Patients are followed at week 48, every 4 months for 1 year, and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 375 patients will be accrued for this study within 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 183 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Study of Radiation Therapy (RT) and O6-Benzylguanine (O6-BG) Plus BCNU Versus RT and BCNU Alone for Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma
• Study Start Date: Sep 1, 2001
• Actual Primary Completion Date: May 1, 2006
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: O6-BG + BCNU + Radiation Therapy O6-BG: 120 mg/m^2 IV over 1 hour on day 1 of each cycle BCNU: 40 mg/m^2 IV over 1 hour on day 1 of each cycle 6 hours after O6-BG dose. Radiation Therapy: 5 days/week using one fraction per day and a dose of 180 cGy per fraction. Initial target volume is dose of 5040 cGy in 28 fractions with boost target volume of 1080 cGy in 6 fractions.	Drug: carmustine; 40 mg/m^2 IV over 1 hour on day 1 of each cycle 6 hours after O6-BG dose for experimental arm with O6=BG. 200 mg/m^2 IV over 1 hour on day 2 of each cycle for the active comparator arm.; Radiation: radiation therapy; 5 days/week using one fraction per day and a dose of 180 cGy per fraction. Initial target volume is dose of 5040 cGy in 28 fractions with boost target volume of 1080 cGy in 6 fractions.; Drug: O6-Benzylguanine; 120 mg/m^2 IV over 1 hour on day 1 of each cycle; Other Names: O6-BG
Active Comparator: BCNU + Radiation Therapy BCNU: 40 mg/m^2 IV over 1 hour on day 1 of each cycle. Radiation Therapy: 5 days/week using one fraction per day and a dose of 180 cGy per fraction. Initial target volume is dose of 5040 cGy in 28 fractions with boost target volume of 1080 cGy in 6 fractions.	Drug: carmustine; 40 mg/m^2 IV over 1 hour on day 1 of each cycle 6 hours after O6-BG dose for experimental arm with O6=BG. 200 mg/m^2 IV over 1 hour on day 2 of each cycle for the active comparator arm.; Radiation: radiation therapy; 5 days/week using one fraction per day and a dose of 180 cGy per fraction. Initial target volume is dose of 5040 cGy in 28 fractions with boost target volume of 1080 cGy in 6 fractions.

Outcome Measures

Primary Outcome Measures

1. Survival [assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5]

Secondary Outcome Measures

1. Progression-free survival [assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5]

2. Time to treatment failure [assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5]

3. Toxicity [assessed weekly for 42 weeks]

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme or gliosarcoma

• Biopsy or surgical resection within the past 28 days

• MRI* with gadolinium performed before registration

• Patients who undergo a simple biopsy only require preoperative MRI* with gadolinium

• No more than 2 noncontiguous tumor sites based on T2-weighted MRI (in 3 dimensions)*

• No prior radiotherapy-delivered cephalad to the interspace between the seventh cervical and the first thoracic vertebral body NOTE: *If an MRI is not medically feasible, patients may have a CT scan with contrast

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 3,000/mm^3

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

• Hemoglobin at least 8 g/dL

Hepatic:

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

• SGOT/SGPT no greater than 2 times ULN

• Alkaline phosphatase no greater than 2 times ULN

• PT/PTT no greater than 1.2 times ULN

Renal:

• Not specified

Cardiac:

• No severe cardiac disease, including any of the following:

• Uncontrolled arrhythmias or conduction defects

• Major problems with edema (e.g., residual swelling in the legs from deep vein thrombosis)

• Recent coronary artery disease

• Poorly controlled hypertension (i.e., diastolic blood pressure greater than 110 mm Hg and/or systolic blood pressure greater than 180 mm Hg)

Pulmonary:

• DLCO at least 70% of predicted

• No severe pulmonary disease

Other:

• HIV negative

• No severe Cushing's syndrome

• No known allergies to any of the study drugs

• No major psychiatric illness

• No poorly controlled diabetes complicated by steroid treatment

• No other medical illness that cannot be adequately controlled or that would preclude study participation

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

• No other concurrent antitumor chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except postmenopausal estrogen replacement therapy

• Corticosteroids at stable or decreasing dose for tumor edema allowed

Radiotherapy:

• See Disease Characteristics

• No prior radiotherapy

• No other concurrent radiotherapy (including intensity-modulated radiotherapy) to the index lesion(s)

Surgery:

• See Disease Characteristics

• No concurrent antitumor surgery

Other:

• No other concurrent investigational drugs

• No other concurrent antineoplastic drugs or therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Regional Hospital Cancer Center	Anchorage	Alaska	United States	99508
2	Banner Good Samaritan Medical Center	Phoenix	Arizona	United States	85006
3	CCOP - Western Regional, Arizona	Phoenix	Arizona	United States	85006
4	St. Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
5	Banner Thunderbird Medical Center	Phoenix	Arizona	United States	85306
6	North Bay Cancer Center	Fairfield	California	United States	94533
7	Memorial Hospital Cancer Center	Colorado Springs	Colorado	United States	80909
8	St. Anthony Central Hospital	Denver	Colorado	United States	80204
9	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Denver	Colorado	United States	80217-3364
10	North Colorado Medical Center	Greeley	Colorado	United States	80631
11	McKee Medical Center	Loveland	Colorado	United States	80539
12	St. Anthony North Hospital	Westminster	Colorado	United States	80030
13	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
14	West Florida Cancer Institute at West Florida Hospital - Pensacola	Pensacola	Florida	United States	32514
15	Piedmont Hospital	Atlanta	Georgia	United States	30309
16	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342
17	Northside Hospital Cancer Center	Atlanta	Georgia	United States	30342
18	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia	United States	30342
19	WellStar Cobb Hospital	Austell	Georgia	United States	30106
20	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia	United States	30033
21	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
22	Gwinnett Medical Center	Lawrenceville	Georgia	United States	30045
23	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
24	Southern Regional Medical Center	Riverdale	Georgia	United States	30274
25	Hematology Oncology Associates of Eastern Idaho	Idaho Falls	Idaho	United States	83404
26	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
27	University of Illinois at Chicago Cancer Center	Chicago	Illinois	United States	60612
28	Veterans Affairs Medical Center - Chicago Westside Hospital	Chicago	Illinois	United States	60612
29	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
30	Good Samaritan Regional Health Center	Mt. Vernon	Illinois	United States	62864
31	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
32	St. Francis Hospital and Health Centers	Beech Grove	Indiana	United States	46107
33	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa	United States	52803
34	Genesis Medical Center - West Campus	Davenport	Iowa	United States	52804
35	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
36	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
37	Cancer Center of Kansas, P.A. - El Dorado	El Dorado	Kansas	United States	67042
38	Veterans Affairs Medical Center - Kansas City	Kansas City	Kansas	United States	64128
39	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160
40	Cancer Center of Kansas - Kingman	Kingman	Kansas	United States	67068
41	Southwest Medical Center	Liberal	Kansas	United States	67901
42	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
43	Cancer Center of Kansas, P.A. - Parsons	Parsons	Kansas	United States	67357
44	Pratt Cancer Center of Kansas	Pratt	Kansas	United States	67124
45	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67042
46	Salina Regional Health Center	Salina	Kansas	United States	67401
47	Stormont-Vail Cancer Center	Topeka	Kansas	United States	66604
48	St. Francis Comprehensive Cancer Center	Topeka	Kansas	United States	66606
49	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
50	Associates in Womens Health	Wichita	Kansas	United States	67203
51	Cancer Center of Kansas, P.A.	Wichita	Kansas	United States	67208
52	Cancer Center of Kansas, P.A. - Wichita	Wichita	Kansas	United States	67214
53	CCOP - Wichita	Wichita	Kansas	United States	67214
54	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
55	Wesley Medical Center	Wichita	Kansas	United States	67214
56	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
57	Baton Rouge General Regional Cancer Center	Baton Rouge	Louisiana	United States	70806
58	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana	United States	70809
59	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
60	Medical Center of Louisiana - New Orleans	New Orleans	Louisiana	United States	70112
61	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
62	Mecosta County General Hospital	Big Rapids	Michigan	United States	49307
63	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
64	Lacks Cancer Center at Saint Mary's Mercy Medical Center	Grand Rapids	Michigan	United States	49503
65	Spectrum Health Cancer Care - Butterworth Campus	Grand Rapids	Michigan	United States	49503
66	Metropolitan Hospital	Grand Rapids	Michigan	United States	49506
67	Holland Community Hospital	Holland	Michigan	United States	49423
68	Hackley Hospital	Muskegon	Michigan	United States	49443
69	Northern Michigan Hospital	Petoskey	Michigan	United States	49770
70	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
71	Munson Medical Center	Traverse City	Michigan	United States	49684
72	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
73	St. Francis Medical Center	Cape Girardeau	Missouri	United States	63701
74	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Gape Girardeau	Missouri	United States	63701
75	Freeman Cancer Institute at Freeman Health System	Joplin	Missouri	United States	64804
76	CCOP - Kansas City	Kansas City	Missouri	United States	64131
77	St. John's Regional Health Center	Springfield	Missouri	United States	65804
78	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
79	CCOP - St. Louis-Cape Girardeau	St. Louis	Missouri	United States	63141
80	David C. Pratt Cancer Center at St. John's Mercy	St. Louis	Missouri	United States	63141
81	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
82	Deaconess Billings Clinic - Downtown	Billings	Montana	United States	59101
83	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
84	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
85	St. Vincent Healthcare	Billings	Montana	United States	59101
86	Deaconess Billings Clinic Cancer Center	Billings	Montana	United States	59107
87	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
88	Internal Medicine Associates of Bozeman	Bozeman	Montana	United States	59715
89	St. James Community Hospital	Butte	Montana	United States	59701
90	Great Falls Clinic	Great Falls	Montana	United States	59405
91	Sletten Regional Cancer Institute	Great Falls	Montana	United States	59405
92	St. Peter's Hospital	Helena	Montana	United States	59601
93	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
94	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
95	Eastern Montana Cancer Center	Miles City	Montana	United States	59301
96	Community Medical Center	Missoula	Montana	United States	59801
97	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59802
98	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59802
99	Good Samaritan Health Systems	Kearney	Nebraska	United States	68847
100	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
101	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233
102	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
103	Adena Regional Medical Center	Chillicothe	Ohio	United States	54601
104	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
105	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214
106	CCOP - Columbus	Columbus	Ohio	United States	43215
107	Grant Riverside Cancer Services	Columbus	Ohio	United States	43215
108	Mount Carmel West Hospital	Columbus	Ohio	United States	43222
109	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
110	Grandview Hospital	Dayton	Ohio	United States	45405
111	Good Samaritan Hospital	Dayton	Ohio	United States	45406
112	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
113	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
114	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
115	CCOP - Dayton	Dayton	Ohio	United States	45429
116	Grady Memorial Hospital	Delaware	Ohio	United States	43015
117	Community Oncology Group - Independence	Independence	Ohio	United States	44131
118	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
119	Fairfield Medical Center	Lancaster	Ohio	United States	43130
120	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
121	Middletown Regional Hospital	Middletown	Ohio	United States	45044
122	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
123	Mercy Medical Center Oncology Unit	Springfield	Ohio	United States	45504
124	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
125	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373
126	Mount Carmel Cancer Services at Mount Carmel St. Ann's Hospital	Westerville	Ohio	United States	43081
127	Cleveland Clinic - Wooster	Wooster	Ohio	United States	44691
128	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
129	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
130	Legacy Mount Hood Medical Center	Glesham	Oregon	United States	97030
131	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
132	Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center	Portland	Oregon	United States	97210
133	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213
134	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
135	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
136	Institute of Oncology at Vilnius University	Portland	Oregon	United States	97227
137	Salem Hospital Regional Cancer Center	Salem	Oregon	United States	97309
138	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
139	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee	United States	37660
140	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
141	Wilford Hall Medical Center	Lackland AFB	Texas	United States	78236
142	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
143	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84112
144	Danville Regional Medical Center	Danville	Virginia	United States	24541
145	St. Joseph Hospital Community Cancer Center	Bellingham	Washington	United States	98225
146	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
147	St. Francis Hospital	Federal Way	Washington	United States	98003
148	Skagit Valley Hospital Cancer Care Center	Mt. Vernon	Washington	United States	98273
149	Capital Medical Center	Olympia	Washington	United States	98507
150	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98104
151	Group Health Central Hospital	Seattle	Washington	United States	98104
152	Harborview Medical Center	Seattle	Washington	United States	98104
153	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98114
154	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195
155	North Puget Oncology at United General Hospital	Sedro-Wooley	Washington	United States	98284
156	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
157	Allenmore Hospital	Tacoma	Washington	United States	98405
158	CCOP - Northwest	Tacoma	Washington	United States	98405
159	St. Clare Hospital	Tacoma	Washington	United States	98499
160	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
161	Central Washington Hospital	Wenatchee	Washington	United States	98801
162	Wenatchee Valley Clinic	Wenatchee	Washington	United States	98801
163	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Deborah T. Blumenthal, MD, University of Utah
• Study Chair: Alexander M. Spence, MD, University of Washington
• Study Chair: Keith J. Stelzer, MD, PhD, Celilo Cancer Center at Mid-Columbia Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00017147
• Other Study ID Numbers: CDR0000068656; S0001; U10CA032102
• First Posted: Jan 27, 2003
• Last Update Posted: Jan 30, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by Southwest Oncology Group: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma
• Additional relevant MeSH terms: Glioblastoma; Neoplasms; Gliosarcoma; Eye Neoplasms; Carmustine; O(6)-benzylguanine

Study Results

No Results Posted as of Jan 30, 2013