Temozolomide Plus Lomustine Followed by Radiation Therapy in Treating Patients With High-Grade Malignant Glioma

Sponsor
Children's Oncology Group (Other)
Overall Status
Completed
CT.gov ID
NCT00006024
Collaborator
National Cancer Institute (NCI) (NIH)
32
235
1
70
0.1
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. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of temozolomide plus lomustine followed by radiation therapy in treating patients who have high-grade malignant glioma.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

OBJECTIVES:
  • Determine the maximum tolerated dose of temozolomide when administered with lomustine in patients with high-grade malignant gliomas.

  • Determine the dose-limiting toxic effects of this regimen in these patients.

  • Evaluate the feasibility of radiotherapy after this treatment regimen in this patient population.

  • Evaluate the radiographic responses in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of temozolomide.

Patients receive oral temozolomide on days 1-5 and oral lomustine on day 1. Treatment continues every 28 days, if blood counts have recovered, for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo radiotherapy on days 1-5 weekly for 6 weeks. Patients continue the same chemotherapy regimen for up to 6 more courses beginning 4 weeks after completion of radiotherapy.

Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.

Study Design

Study Type:
Interventional
Actual Enrollment :
32 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study of Temozolomide and CCNU in Pediatric Patients With Newly Diagnosed Incompletely Resected Non-Brainstem High-Grade Gliomas
Study Start Date :
Nov 1, 2000
Actual Primary Completion Date :
Jan 1, 2005
Actual Study Completion Date :
Sep 1, 2006

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pre and Post radiation Chemotherapy

Drug: lomustine

Drug: temozolomide

Outcome Measures

Primary Outcome Measures

  1. Progression Free Survival [Length of study]

    This trial is a phase I evaluation of temozolomide in combination with a fixed dose of CCNU with the starting dose for temozolomide

Eligibility Criteria

Criteria

Ages Eligible for Study:
3 Years to 21 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
DISEASE CHARACTERISTICS:
  • Histologically confirmed high-grade malignant glioma of one of the following subtypes:

  • Glioblastoma

  • Anaplastic astrocytoma

  • Anaplastic oligoastrocytoma

  • Gliomatosis cerebri

  • No disseminated disease or primary spinal cord malignancies

  • Measurable intracranial residual disease by MRI

PATIENT CHARACTERISTICS:
Age:
  • 3 and over

  • Under 22 at time of diagnosis

Performance status:
  • Karnofsky 50-100% if over 10 years of age

  • Lansky 50-100% if 10 years of age or under

Life expectancy:
  • At least 8 weeks
Hematopoietic:
  • Absolute neutrophil count at least 1,000/mm^3

  • Platelet count at least 100,000/mm^3 (transfusion independent)

  • Hemoglobin at least 8.0 g/dL (RBC transfusions allowed)

Hepatic:
  • Bilirubin no greater than 1.5 times normal for age

  • SGPT no greater than 2.5 times normal for age

  • Albumin at least 2 g/dL

Renal:
  • Creatinine no greater than 1.5 times normal for age OR

  • Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal for age

Pulmonary:
  • No dyspnea at rest

  • No exercise intolerance

  • Pulse oximetry at least 94%

Other:
  • Not pregnant or nursing

  • Negative pregnancy test

  • Fertile patients must use effective contraception

  • No uncontrolled infection

PRIOR CONCURRENT THERAPY:
Biologic therapy:
  • No prior biologic therapy

  • No concurrent prophylactic hematopoietic growth factors

Chemotherapy:
  • No prior chemotherapy
Endocrine therapy:
  • Prior corticosteroid therapy allowed

  • No concurrent corticosteroids as antiemetic

Radiotherapy:
  • No prior radiotherapy
Surgery:
  • No more than 31 days since prior maximal neurosurgical procedure
Other:
  • No concurrent phenobarbital or cimetidine

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Alabama at Birmingham Comprehensive Cancer Center Birmingham Alabama United States 35233
2 University of South Alabama Medical Center Mobile Alabama United States 36604
3 Phoenix Children's Hospital Phoenix Arizona United States 85016-7710
4 Arizona Cancer Center Tucson Arizona United States 85724
5 University of Arkansas for Medical Sciences Little Rock Arkansas United States 72205
6 Southern California Permanente Medical Group Downey California United States 90242
7 City of Hope Comprehensive Cancer Center Duarte California United States 91010-3000
8 Rebecca and John Moores UCSD Cancer Center La Jolla California United States 92093-0658
9 Loma Linda University Medical Center Loma Linda California United States 92354
10 Jonathan Jaques Children's Cancer Center Long Beach California United States 90801-1428
11 Children's Hospital Los Angeles Los Angeles California United States 90027-0700
12 Cedars-Sinai Medical Center Los Angeles California United States 90048
13 Jonsson Comprehensive Cancer Center, UCLA Los Angeles California United States 90095-1781
14 Children's Hospital Central California Madera California United States 93638-8762
15 Children's Hospital of Oakland Oakland California United States 94609-1809
16 Chao Family Comprehensive Cancer Center Orange California United States 92868
17 Children's Hospital of Orange County Orange California United States 92868
18 Lucile Packard Children's Hospital at Stanford Palo Alto California United States 94304
19 Sutter Cancer Center Sacramento California United States 95816
20 University of California Davis Medical Center Sacramento California United States 95817
21 Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego San Diego California United States 92120
22 Children's Hospital San Diego San Diego California United States 92123-4282
23 Kaiser Permanente Medical Center - San Francisco Geary Campus San Francisco California United States 94115
24 UCSF Comprehensive Cancer Center San Francisco California United States 94143-0128
25 Santa Barbara Cottage Hospital Santa Barbara California United States 93102
26 Kaiser Permanente Medical Center - Santa Clara Santa Clara California United States 95051-5386
27 David Grant Medical Center Travis Air Force Base California United States 94535
28 Children's Hospital of Denver Denver Colorado United States 80218-1088
29 Childhood Hematology/Oncology Associates Denver Colorado United States 80218
30 Presbyterian-St Luke's Medical Center Denver Colorado United States 80218
31 University of Connecticut Health Center Farmington Connecticut United States 06360-7106
32 Yale Comprehensive Cancer Center New Haven Connecticut United States 06520-8028
33 Alfred I. Dupont Institute Wilmington Delaware United States 19899
34 Lombardi Cancer Center Washington District of Columbia United States 20007
35 Children's National Medical Center Washington District of Columbia United States 20010-2970
36 Walter Reed Army Medical Center Washington District of Columbia United States 20307-5000
37 Broward General Medical Center Fort Lauderdale Florida United States 33316
38 Children's Hospital of Southwest Florida Fort Myers Florida United States 33908
39 Shands Hospital and Clinics, University of Florida Gainesville Florida United States 32610-100277
40 Joe DiMaggio Children's Hospital at Memorial Hollywood Florida United States 33021
41 Nemours Children's Clinic Jacksonville Florida United States 32207
42 University of Miami-Jackson Memorial Hospital Miami Florida United States 33136
43 Miami Children's Hospital Miami Florida United States 33155-4069
44 Baptist Hospital of Miami Miami Florida United States 33176-2197
45 Florida Hospital Cancer Institute Orlando Florida United States 32803
46 Nemours Children's Clinic-Orlando Orlando Florida United States 32806
47 Sacred Heart Children's Hospital Pensacola Florida United States 32504
48 All Children's Hospital St. Petersburg Florida United States 33701
49 Tampa Children's Hospital Tampa Florida United States 33677-4227
50 St. Mary's Hospital West Palm Beach Florida United States 33407
51 Emory University Hospital - Atlanta Atlanta Georgia United States 30322
52 Children's Healthcare of Atlanta - Scottish Rite Atlanta Georgia United States 30342
53 Medical College of Georgia Comprehensive Cancer Center Augusta Georgia United States 30912-4000
54 Medical Center of Central Georgia Macon Georgia United States 31201
55 Memorial Health University Medical Center, Inc. Savannah Georgia United States 31403-3089
56 Cancer Research Center of Hawaii Honolulu Hawaii United States 96813
57 MBCCOP - Hawaii Honolulu Hawaii United States 96813
58 Tripler Army Medical Center Honolulu Hawaii United States 96859-5000
59 Mountain States Tumor Institute Boise Idaho United States 83712
60 University of Chicago Cancer Research Center Chicago Illinois United States 60601
61 Rush-Presbyterian-St. Luke's Medical Center Chicago Illinois United States 60612
62 University of Illinois at Chicago Chicago Illinois United States 60612
63 Children's Memorial Hospital - Chicago Chicago Illinois United States 60614
64 Hope Children's Hospital Oak Lawn Illinois United States 60453
65 Lutheran General Hospital Park Ridge Illinois United States 60068-1174
66 Saint Jude Midwest Affiliate Peoria Illinois United States 61637
67 Southern Illinois University School of Medicine Springfield Illinois United States 62794-9658
68 Indiana University Cancer Center Indianapolis Indiana United States 46202-5289
69 St. Vincent Hospital and Health Care Center Indianapolis Indiana United States 46260
70 Raymond Blank Memorial Hospital for Children Des Moines Iowa United States 50308
71 John Stoddard Cancer Center Des Moines Iowa United States 50309
72 Holden Comprehensive Cancer Center Iowa City Iowa United States 52242-1009
73 Wesley Medical Center Wichita Kansas United States 67214
74 Albert B. Chandler Medical Center, University of Kentucky Lexington Kentucky United States 40536-0284
75 Kosair Children's Hospital Louisville Kentucky United States 40202-3830
76 Tulane University School of Medicine New Orleans Louisiana United States 70112
77 Children's Hospital of New Orleans New Orleans Louisiana United States 70118
78 Ochsner Clinic New Orleans Louisiana United States 70121
79 Eastern Maine Medical Center Bangor Maine United States 04401
80 Maine Children's Cancer Program Scarborough Maine United States 04074
81 Marlene and Stewart Greenebaum Cancer Center, University of Maryland Baltimore Maryland United States 21201-1595
82 Sinai Hospital of Baltimore Baltimore Maryland United States 21225
83 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland United States 21231-2410
84 Floating Hospital for Children Boston Massachusetts United States 02111
85 Dana-Farber Cancer Institute Boston Massachusetts United States 02115
86 Baystate Medical Center Springfield Massachusetts United States 01107
87 University of Massachusetts Memorial Medical Center - University Campus Worcester Massachusetts United States 01655
88 Mott Children's Hospital Ann Arbor Michigan United States 48109-0914
89 Children's Hospital of Michigan Detroit Michigan United States 48201
90 Henry Ford Hospital Detroit Michigan United States 48202
91 St. John Hospital and Medical Center Detroit Michigan United States 48236
92 Michigan State University East Lansing Michigan United States 48824
93 Hurley Medical Center Flint Michigan United States 48503
94 Spectrum Health and DeVos Children's Hospital Grand Rapids Michigan United States 49503
95 Bronson Methodist Hospital Kalamazoo Michigan United States 49007
96 CCOP - Beaumont Royal Oak Michigan United States 48073-6769
97 William Beaumont Hospital Royal Oak Michigan United States 48073-6769
98 St. Mary's/Duluth Clinic Cancer Center Duluth Minnesota United States 55805-1983
99 Children's Hospitals and Clinics - Minneapolis Minneapolis Minnesota United States 55404
100 Mayo Clinic Cancer Center Rochester Minnesota United States 55905
101 Children's Hospitals and Clinics of Minnesota Saint Paul Minnesota United States 55102
102 University of Mississippi Medical Center Jackson Mississippi United States 39216-4505
103 Children's Mercy Hospital Kansas City Missouri United States 64108
104 Cardinal Glennon Children's Hospital Saint Louis Missouri United States 63104
105 St. Louis Children's Hospital Saint Louis Missouri United States 63110
106 Children's Hospital of Omaha Omaha Nebraska United States 68114
107 University of Nebraska Medical Center Omaha Nebraska United States 68198-2168
108 Sunrise Hospital and Medical Center Las Vegas Nevada United States 89109-2306
109 Norris Cotton Cancer Center Lebanon New Hampshire United States 03756-0002
110 Hackensack University Medical Center Hackensack New Jersey United States 07601
111 Cancer Institute of New Jersey New Brunswick New Jersey United States 08903
112 Newark Beth Israel Medical Center Newark New Jersey United States 07112-2094
113 St. Joseph's Hospital and Medical Center Paterson New Jersey United States 07503
114 Atlantic Health System Summit New Jersey United States 07901
115 University of New Mexico Cancer Research and Treatment Center Albuquerque New Mexico United States 87131
116 Cancer Center of Albany Medical Center Albany New York United States 12208
117 Albert Einstein Clinical Cancer Center Bronx New York United States 10461
118 Brooklyn Hospital Center Brooklyn New York United States 11201
119 State University of New York Health Science Center at Brooklyn College of Medicine Brooklyn New York United States 11203
120 Brookdale University Hospital and Medical Center Brooklyn New York United States 11212
121 Maimonides Medical Center Brooklyn New York United States 11219
122 Roswell Park Cancer Institute Buffalo New York United States 14263-0001
123 North Shore University Hospital Manhasset New York United States 11030
124 Schneider Children's Hospital New Hyde Park New York United States 11042
125 New York Presbyterian Hospital - Cornell Campus New York New York United States 10021-4885
126 Memorial Sloan-Kettering Cancer Center New York New York United States 10021
127 Mount Sinai School of Medicine New York New York United States 10029
128 Columbia Presbyterian Hospital New York New York United States 10032
129 James P. Wilmot Cancer Center Rochester New York United States 14642
130 State University of New York Health Sciences Center - Stony Brook Stony Brook New York United States 11790-7775
131 State University of New York - Upstate Medical University Syracuse New York United States 13210
132 New York Medical College Valhalla New York United States 10595
133 Mission Saint Joseph's Health System Asheville North Carolina United States 28801
134 Lineberger Comprehensive Cancer Center, UNC Chapel Hill North Carolina United States 27599-7295
135 Carolinas Medical Center Charlotte North Carolina United States 28232-2861
136 Presbyterian Healthcare Charlotte North Carolina United States 28233-3549
137 Duke Comprehensive Cancer Center Durham North Carolina United States 27710
138 East Carolina University School of Medicine Greenville North Carolina United States 27858-4354
139 Comprehensive Cancer Center at Wake Forest University Winston-Salem North Carolina United States 27157-1081
140 Dakota Cancer Institute Fargo North Dakota United States 58103-4940
141 Children's Hospital Medical Center of Akron Akron Ohio United States 44308
142 Children's Hospital Medical Center - Cincinnati Cincinnati Ohio United States 45229-3039
143 Ireland Cancer Center Cleveland Ohio United States 44106-5065
144 Cleveland Clinic Taussig Cancer Center Cleveland Ohio United States 44195
145 Children's Hospital of Columbus Columbus Ohio United States 43205-2696
146 Children's Medical Center - Dayton Dayton Ohio United States 45404
147 Toledo Children's Hospital Toledo Ohio United States 43601
148 St. Vincent Mercy Medical Center Toledo Ohio United States 43608
149 Forum Health-Tod Childrens Hospital Youngstown Ohio United States 44501
150 Children's Hospital of Oklahoma Oklahoma City Oklahoma United States 73104
151 CCOP - Oklahoma Tulsa Oklahoma United States 74136
152 Natalie Warren Bryant Cancer Center Tulsa Oklahoma United States 74136
153 Doernbecher Children's Hospital Portland Oregon United States 97201-3098
154 Legacy Emanuel Hospital and Health Center Portland Oregon United States 97227
155 Geisinger Medical Center Danville Pennsylvania United States 17822-1320
156 Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033-0850
157 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
158 St. Christopher's Hospital for Children Philadelphia Pennsylvania United States 19134-1095
159 Children's Hospital of Pittsburgh Pittsburgh Pennsylvania United States 15213
160 Rhode Island Hospital Providence Rhode Island United States 02818
161 Medical University of South Carolina Charleston South Carolina United States 29425-0721
162 Palmetto Health South Carolina Cancer Center Columbia South Carolina United States 29203
163 Children's Hospital of Greenville Hospital System Greenville South Carolina United States 29605
164 Avera Cancer Institute Sioux Falls South Dakota United States 57105-1080
165 Sioux Valley Hospital Sioux Falls South Dakota United States 57117
166 East Tennessee State University Cancer Center at JCMC Johnson City Tennessee United States 37604
167 East Tennessee Children's Hospital Knoxville Tennessee United States 37901
168 Saint Jude Children's Research Hospital Memphis Tennessee United States 38105-2794
169 Vanderbilt-Ingram Cancer Center Nashville Tennessee United States 37232-6838
170 Texas Tech University Health Sciences Center School of Medicine Amarillo Texas United States 79106
171 Children's Hospital of Austin Austin Texas United States 78701
172 Medical City Dallas Hospital Dallas Texas United States 75230
173 Simmons Cancer Center - Dallas Dallas Texas United States 75235-9154
174 Cook Children's Medical Center - Fort Worth Fort Worth Texas United States 76104
175 University of Texas Medical Branch Galveston Texas United States 77555-0361
176 University of Texas - MD Anderson Cancer Center Houston Texas United States 77030-4009
177 Baylor College of Medicine Houston Texas United States 77030
178 San Antonio Military Pediatric Cancer and Blood Disorders Center Lackland Air Force Base Texas United States 78236-5300
179 Covenant Children's Hospital Lubbock Texas United States 79410
180 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78207
181 Methodist Health Care System San Antonio Texas United States 78229-3902
182 Scott and White Memorial Hospital Temple Texas United States 76508
183 Huntsman Cancer Institute Salt Lake City Utah United States 84112
184 Vermont Cancer Center Burlington Vermont United States 05401-3498
185 Cancer Center at the University of Virginia Charlottesville Virginia United States 22908
186 Inova Fairfax Hospital Falls Church Virginia United States 22042-3300
187 Children's Hospital of the King's Daughters Norfolk Virginia United States 23507
188 Naval Medical Center, Portsmouth Portsmouth Virginia United States 23708-5100
189 Massey Cancer Center Richmond Virginia United States 23298-0037
190 Carilion Medical Center for Children Roanoke Virginia United States 24013
191 Children's Hospital and Regional Medical Center - Seattle Seattle Washington United States 98105
192 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109-1024
193 Group Health Cooperative Seattle Washington United States 98112
194 Deaconess Medical Center Spokane Washington United States 99210-0248
195 Mary Bridge Children's Health Center Tacoma Washington United States 98415-0299
196 Madigan Army Medical Center Tacoma Washington United States 98431-5000
197 West Virginia University - Charleston Charleston West Virginia United States 25302
198 Cabell-Huntington Hospital, Inc Huntington West Virginia United States 25701
199 West Virginia University Hospitals Morgantown West Virginia United States 26506-9300
200 Bellin Memorial Hospital Green Bay Wisconsin United States 54301
201 CCOP - St. Vincent Hospital Cancer Center, Green Bay Green Bay Wisconsin United States 54301
202 St. Vincent Hospital Green Bay Wisconsin United States 54307-9070
203 Gundersen Lutheran Medical Center La Crosse Wisconsin United States 54601
204 University of Wisconsin Hospital and Clinics Madison Wisconsin United States 53792-0001
205 Marshfield Clinic Marshfield Wisconsin United States 54449-5772
206 Midwest Children's Cancer Center Milwaukee Wisconsin United States 53226
207 Sydney Children's Hospital Randwick New South Wales Australia 2031
208 Children's Hospital at Westmead Westmead New South Wales Australia 2145
209 Royal Children's Hospital Brisbane Queensland Australia 4029
210 Women's and Children's Hospital North Adelaide South Australia Australia 5006
211 Royal Children's Hospital Parkville Victoria Australia 3052
212 Princess Margaret Hospital for Children Perth Western Australia Australia 6001
213 Alberta Children's Hospital Calgary Alberta Canada T2T 5C7
214 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
215 British Columbia Children's Hospital Vancouver British Columbia Canada V6H 3V4
216 CancerCare Manitoba Winnipeg Manitoba Canada R3E 0V9
217 Janeway Children's Health and Rehabilitation Centre St. John's Newfoundland and Labrador Canada A1B 3V6
218 IWK Health Centre Halifax Nova Scotia Canada B3J 3G9
219 Children's Hospital Hamilton Ontario Canada L8N 3Z5
220 Children's Hospital of Western Ontario London Ontario Canada N6C 2V5
221 Children's Hospital of Eastern Ontario Ottawa Ontario Canada K1H 8L1
222 Hospital for Sick Children Toronto Ontario Canada M5G 1X8
223 McGill University Health Center - Montreal Children's Hospital Montreal Quebec Canada H3H 1P3
224 Hopital Sainte Justine Montreal Quebec Canada H3T 1C5
225 Centre Hospitalier de L'Universite Laval Sainte Foy Quebec Canada GIV 4G2
226 Laval University Medical Center Sainte-Foy Quebec Canada G1V 4G2
227 Allan Blair Cancer Centre Regina Saskatchewan Canada S4T 7T1
228 Saskatoon Cancer Centre Saskatoon Saskatchewan Canada S7N 4H4
229 Academisch Ziekenhuis Groningen Groningen Netherlands 9700 RB
230 Starship Children's Hospital Auckland New Zealand
231 University of Puerto Rico School of Medicine Medical Sciences Campus San Juan Puerto Rico 00936-5067
232 San Jorge Childrens Hospital Santurce Puerto Rico 00912
233 Swiss Pediatric Oncology Group Bern Bern Switzerland CH 3010
234 Swiss Pediatric Oncology Group Geneva Geneva Switzerland CH 1211
235 Swiss Pediatric Oncology Group Lausanne Lausanne Switzerland CH 1011

Sponsors and Collaborators

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

Investigators

  • Study Chair: Regina Jakacki, MD, University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00006024
Other Study ID Numbers:
  • ADVL0011
  • COG-ADVL0011
  • CCG-ADVL0011
  • CCG-A0993
  • CDR0000068036
First Posted:
Jan 27, 2003
Last Update Posted:
Feb 13, 2014
Last Verified:
Feb 1, 2014
Keywords provided by Children's Oncology Group
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 13, 2014