Radiation Therapy, Temozolomide, and Lomustine in Treating Young Patients With Newly Diagnosed Gliomas

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00100802
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 118
• Locations: 150
• Arm: 1
• Duration (Months): 144
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and lomustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with temozolomide and lomustine after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with temozolomide and lomustine works in treating young patients with newly diagnosed gliomas.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumors; Central Nervous System Tumors	Drug: lomustine; Drug: temozolomide; Procedure: adjuvant therapy; Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

• Compare event-free survival of pediatric patients with newly diagnosed high-grade gliomas treated with adjuvant radiotherapy and temozolomide followed by temozolomide and lomustine with historical controls.

• Determine the toxicity of this regimen in these patients.

• Correlate MGMT and p53 expression in tumor tissue with outcome in patients treated with this regimen.

• Correlate polymorphisms in GSTP1, GSTM1, and GSTT1 genes and GSTP1 protein expression in tumors with survival in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

• Chemoradiotherapy: Patients receive oral temozolomide once daily on days 1-42. Patients also undergo concurrent radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients who did not undergo prior gross total resection also undergo boost radiotherapy once daily on days 43-47.

• Maintenance chemotherapy: Four weeks after completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5 and oral lomustine on day 1. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 50-100 patients will be accrued for this study within 1-1.5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 118 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Concurrent Radiation and Temozolomide Followed By Temozolomide and CCNU in the Treatment of Children With High-Grade Glioma
• Study Start Date: Jul 1, 2005
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Jun 30, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Surgery, Chemoradiotherapy, Rest, Maintenance, FUP Patients must begin therapy within 31 days of surgery. Chemoradiotherapy = Radiation Therapy Dose: 54.0 Gy with a Boost of 5.4 Gy Temozolomide 90mg/m2/day daily for 42 days. Maintenance consists of 6 treatment cycles of combo chemotherapy with lomustine and temozolomide. Maintenance will begin 4 weeks following radiation. Five days of temozolomide (day 1 - 5) and one dose of lomustine (day 1) followed by 36 days of rest = 1 treatment cycle.

Drug: lomustine; Capsule; Other Names: Ceenu NSC #79037 ; Drug: temozolomide; Capsule; Other Names: Temodar NSC # 362856 ; Procedure: adjuvant therapy; Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures

1. One Year Overall Survival [One year]

   Estimated one year survival using the Kaplan-Meier methodology.

2. Occurrence of Death Attributable to Complications of Protocol Therapy [While receiving protocol therapy (up to 301 days excluding delays) or within 30 days of Termination of Protocol Therapy]

   Number of deaths due to complications of protocol therapy.

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, newly diagnosed high-grade glioma of 1 of the following histologies:

• Anaplastic astrocytoma

• Glioblastoma multiforme

• Gliosarcoma

• Primary spinal cord malignant gliomas allowed

• No primary brainstem tumors

• Has undergone surgical resection or biopsy of the tumor within the past 31 days

• Pre-operative and post-operative brain MRI with and without gadolinium-contrast OR pre-operative and post-operative spine MRI for spinal cord primaries

• Post-operative MRI not required for patients who undergo biopsy only

• No evidence of neuraxis dissemination

• Spine MRI and cerebrospinal fluid cytology required only if clinically indicated

PATIENT CHARACTERISTICS:

Age

• 3 to 21

Performance status

• Karnofsky 50-100% (for patients > 16 years of age)

• Lansky 50-100% (for patients ≤ 16 years of age)

Life expectancy

• At least 8 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3

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

• Hemoglobin ≥ 8 g/dL (transfusions allowed)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• ALT ≤ 2.5 times ULN

• Albumin ≥ 2 g/dL

Renal

• Creatinine ≤ 1.5 times ULN OR

• Creatinine clearance or radioisotope glomerular filtration rate ≥ lower limit of normal

Pulmonary

• No evidence of dyspnea at rest

• No exercise intolerance

• Pulse oximetry ≥ 94% (if determination is clinically indicated)

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 2 months after study participation

• Able to swallow oral medication

• Seizures allowed provided they are well controlled with anticonvulsants

• No hypersensitivity to temozolomide

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior biologic agents

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Prior corticosteroids allowed

• No concurrent corticosteroids as an antiemetic

• Concurrent corticosteroids allowed only for treatment of increased intracranial pressure

Radiotherapy

• No concurrent radiotherapy using cobalt-60

Surgery

• See Disease Characteristics

Other

• No other prior treatment

• No concurrent phenobarbital or cimetidine

• No concurrent co-trimoxazole for Pneumocystis carinii pneumonia prophylaxis during study chemoradiotherapy

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	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016-7710
3	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Southern California Permanente Medical Group	Downey	California	United States	90242-2814
5	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California	United States	92354
6	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California	United States	90801
7	Childrens Hospital Los Angeles	Los Angeles	California	United States	90027
8	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center	Los Angeles	California	United States	90048-1865
9	Children's Hospital & Research Center Oakland	Oakland	California	United States	94609-1809
10	Children's Hospital of Orange County	Orange	California	United States	92868
11	Sutter Cancer Center	Sacramento	California	United States	95816
12	University of California Davis Cancer Center	Sacramento	California	United States	95817
13	Kaiser Permanente Medical Center - Oakland	Sacramento	California	United States	95825
14	Children's Hospital and Health Center - San Diego	San Diego	California	United States	92123-4282
15	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
16	Stanford Comprehensive Cancer Center - Stanford	Stanford	California	United States	94305
17	Children's Hospital Cancer Center	Denver	Colorado	United States	80218-1088
18	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut	United States	06360-2875
19	Alfred I. duPont Hospital for Children	Wilmington	Delaware	United States	19899
20	Broward General Medical Center Cancer Center	Fort Lauderdale	Florida	United States	33316
21	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida	United States	33901
22	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0232
23	Miami Children's Hospital	Miami	Florida	United States	33155
24	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida	United States	32803-1273
25	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida	United States	32504
26	All Children's Hospital	Saint Petersburg	Florida	United States	33701
27	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida	United States	33607
28	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida	United States	33407
29	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
30	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912-3730
31	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60614
32	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
33	Advocate Christ Medical Center	Oak Lawn	Illinois	United States	60453
34	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois	United States	60068-1174
35	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
36	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62794-9620
37	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
38	St. Vincent Indianapolis Hospital	Indianapolis	Indiana	United States	46260
39	Blank Children's Hospital	Des Moines	Iowa	United States	50309
40	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1002
41	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
42	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0293
43	Kosair Children's Hospital	Louisville	Kentucky	United States	40232
44	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana	United States	71315-3198
45	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
46	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine	United States	04401
47	Maine Children's Cancer Program at Barbara Bush Children's Hospital	Scarborough	Maine	United States	04074-9308
48	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
49	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
50	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
51	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
52	Hurley Medical Center	Flint	Michigan	United States	48503
53	Spectrum Health Hospital - Butterworth Campus	Grand Rapids	Michigan	United States	49503-2560
54	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
55	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan	United States	48910
56	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
57	University of Minnesota Children's Hospital - Fairview	Minneapolis	Minnesota	United States	55455
58	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
59	University of Mississippi Cancer Clinic	Jackson	Mississippi	United States	39216-4505
60	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
61	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
62	Cardinal Glennon Children's Hospital	Saint Louis	Missouri	United States	63104
63	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
64	Children's Hospital	Omaha	Nebraska	United States	68114-4113
65	Sunrise Hospital and Medical Center	Las Vegas	Nevada	United States	89109-2306
66	Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
67	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey	United States	07601
68	Overlook Hospital	Morristown	New Jersey	United States	07962
69	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
70	St. Joseph's Hospital and Medical Center	Paterson	New Jersey	United States	07503
71	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico	United States	87131-5636
72	Albany Medical Center Hospital	Albany	New York	United States	12208-3419
73	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York	United States	10461
74	Brooklyn Hospital Center	Brooklyn	New York	United States	11201-5493
75	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
76	Winthrop University Hospital	Mineola	New York	United States	11501
77	Schneider Children's Hospital	New Hyde Park	New York	United States	11040
78	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
79	Memorial Sloan - Kettering Cancer Center	New York	New York	United States	10021-6094
80	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York	United States	10032
81	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
82	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
83	New York Medical College	Valhalla	New York	United States	10595
84	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
85	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
86	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
87	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
88	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
89	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308-1062
90	Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106-5000
91	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195-5217
92	Columbus Children's Hospital	Columbus	Ohio	United States	43205-2696
93	Children's Medical Center - Dayton	Dayton	Ohio	United States	45404-1815
94	Toledo Hospital	Toledo	Ohio	United States	43606
95	Tod Children's Hospital	Youngstown	Ohio	United States	44501
96	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
97	Legacy Emanuel Hospital and Health Center & Children's Hospital	Portland	Oregon	United States	97227
98	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
99	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134-1095
100	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
101	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island	United States	02903
102	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
103	Palmetto Health South Carolina Cancer Center	Columbia	South Carolina	United States	29203
104	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
105	East Tennessee Children's Hospital	Knoxville	Tennessee	United States	37901
106	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
107	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas	United States	79106
108	Children's Hospital of Austin	Austin	Texas	United States	78701
109	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
110	Medical City Dallas Hospital	Dallas	Texas	United States	75230
111	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
112	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104-9958
113	Baylor University Medical Center - Houston	Houston	Texas	United States	77030-2399
114	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78207
115	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229-3993
116	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
117	Primary Children's Medical Center	Salt Lake City	Utah	United States	84113-1100
118	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05405
119	INOVA Fairfax Hospital	Fairfax	Virginia	United States	22031
120	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507-1971
121	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037
122	Carilion Cancer Center of Western Virginia	Roanoke	Virginia	United States	24029
123	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
124	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington	United States	99220-2555
125	Madigan Army Medical Center - Tacoma	Tacoma	Washington	United States	98431
126	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia	United States	25701
127	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
128	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
129	John Hunter Hospital	Newcastle	New South Wales	Australia	2310
130	Westmead Institute for Cancer Research at Westmead Hospital	Westmead	New South Wales	Australia	2145
131	Royal Children's Hospital	Herston, Brisbane	Queensland	Australia	4029
132	Women's and Children's Hospital	North Adelaide	South Australia	Australia	5006
133	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
134	CHUS-Hopital Fleurimont	Sherbrooke	Alberta	Canada	J1H5N4
135	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia	Canada	V6H 3V4
136	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
137	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
138	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
139	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	K7L 3N6
140	Children's Hospital of Western Ontario	London	Ontario	Canada	N6A 4G5
141	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
142	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec	Canada	H3H 1P3
143	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5
144	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan	Canada	S7N 4H4
145	Centre Hospitalier Universitaire de Quebec	Quebec		Canada	G1V 4G2
146	Starship Children's Health	Auckland		New Zealand	1
147	Christchurch Hospital	Christchurch		New Zealand
148	Wellington Children's Hospital	Wellington		New Zealand	6002
149	San Jorge Children's Hospital	Santurce		Puerto Rico	00912
150	Swiss Pediatric Oncology Group Geneva	Geneva		Switzerland	1205

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

• Pollack IF, Hamilton RL, Burger PC, Brat DJ, Rosenblum MK, Murdoch GH, Nikiforova MN, Holmes EJ, Zhou T, Cohen KJ, Jakacki RI; Children's Oncology Group. Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the Children's Oncology Group. J Neurooncol. 2010 Sep;99(2):155-63. doi: 10.1007/s11060-010-0297-3. Epub 2010 Jul 4.
• Pollack IF, Hamilton RL, Sobol RW, Nikiforova MN, Nikiforov YE, Lyons-Weiler MA, LaFramboise WA, Burger PC, Brat DJ, Rosenblum MK, Gilles FH, Yates AJ, Zhou T, Cohen KJ, Finlay JL, Jakacki RI; Children's Oncology Group. Mismatch repair deficiency is an uncommon mechanism of alkylator resistance in pediatric malignant gliomas: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2010 Dec 1;55(6):1066-71. doi: 10.1002/pbc.22634.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00100802
• Other Study ID Numbers: ACNS0423; CDR0000407744; COG-ACNS0423; NCI-2012-02645; U10CA098543
• First Posted: Jan 7, 2005
• Last Update Posted: Aug 7, 2019
• Last Verified: Nov 1, 2016

• Keywords provided by Children's Oncology Group: childhood high-grade cerebral astrocytoma; childhood spinal cord neoplasm
• Additional relevant MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms; Temozolomide; Lomustine

Study Results

Participant Flow

Arm/Group Title	Surgery, Chemoradiotherapy, Rest, Maintenance, Follow-up
Arm/Group Description	Patients must begin therapy within 31 days of surgery. Chemoradiotherapy = Radiation Therapy Dose: 54.0 Gy with a Boost of 5.4 Gy Temozolomide 90mg/m2/day daily for 42 days. Maintenance consists of 6 treatment cycles of combo chemotherapy with lomustine and temozolomide. Maintenance will begin 4 weeks following radiation. Five days of temozolomide (day 1 - 5) and one dose of lomustine (day 1) followed by 36 days of rest = 1 treatment cycle. lomustine: Capsule temozolomide: Capsule adjuvant therapy radiation therapy
Period Title: Overall Study
STARTED	118
COMPLETED	38
NOT COMPLETED	80

Baseline Characteristics

Arm/Group Title	Surgery, Chemoradiotherapy, Rest, Maintenance, FUP
Arm/Group Description	Patients must begin therapy within 31 days of surgery. Chemoradiotherapy = Radiation Therapy Dose: 54.0 Gy with a Boost of 5.4 Gy Temozolomide 90mg/m2/day daily for 42 days. Maintenance consists of 6 treatment cycles of combo chemotherapy with lomustine and temozolomide. Maintenance will begin 4 weeks following radiation. Five days of temozolomide (day 1 - 5) and one dose of lomustine (day 1) followed by 36 days of rest = 1 treatment cycle. lomustine: Capsule temozolomide: Capsule adjuvant therapy radiation therapy
Overall Participants	118
Age (Count of Participants)
<=18 years	110 93.2%
Between 18 and 65 years	8 6.8%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	12
Sex: Female, Male (Count of Participants)
Female	55 46.6%
Male	63 53.4%
Region of Enrollment (participants) [Number]
Canada	15 12.7%
New Zealand	1 0.8%
United States	98 83.1%
Australia	4 3.4%

Outcome Measures

1. Primary Outcome

Title	One Year Overall Survival
Description	Estimated one year survival using the Kaplan-Meier methodology.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

Population is based on 106 eligible patients out of 118 patients enrolled.

Arm/Group Title	Surgery, Chemoradiotherapy, Rest, Maintenance, FUP
Arm/Group Description	Patients must begin therapy within 31 days of surgery. Chemoradiotherapy = Radiation Therapy Dose: 54.0 Gy with a Boost of 5.4 Gy Temozolomide 90mg/m2/day daily for 42 days. Maintenance consists of 6 treatment cycles of combo chemotherapy with lomustine and temozolomide. Maintenance will begin 4 weeks following radiation. Five days of temozolomide (day 1 - 5) and one dose of lomustine (day 1) followed by 36 days of rest = 1 treatment cycle. lomustine: Capsule temozolomide: Capsule adjuvant therapy radiation therapy
Measure Participants	106
Number (95% Confidence Interval) [Estimated probability]	0.7208

2. Primary Outcome

Title	Occurrence of Death Attributable to Complications of Protocol Therapy
Description	Number of deaths due to complications of protocol therapy.
Time Frame	While receiving protocol therapy (up to 301 days excluding delays) or within 30 days of Termination of Protocol Therapy

Outcome Measure Data

Analysis Population Description

106 eligible patients out of 118 patients enrolled is the population basis for this outcome measure.

Arm/Group Title	Surgery, Chemoradiotherapy, Rest, Maintenance, FUP
Arm/Group Description	Patients must begin therapy within 31 days of surgery. Chemoradiotherapy = Radiation Therapy Dose: 54.0 Gy with a Boost of 5.4 Gy Temozolomide 90mg/m2/day daily for 42 days. Maintenance consists of 6 treatment cycles of combo chemotherapy with lomustine and temozolomide. Maintenance will begin 4 weeks following radiation. Five days of temozolomide (day 1 - 5) and one dose of lomustine (day 1) followed by 36 days of rest = 1 treatment cycle. lomustine: Capsule temozolomide: Capsule adjuvant therapy radiation therapy
Measure Participants	106
Number [patients]	1

Adverse Events

Adverse Event Reporting Description	Serious adverse events, only eligible patients are considered. Other adverse events, only eligible patients are considered
Arm/Group Title	Surgery, Chemoradiotherapy, Rest, Maintenance, FUP
Arm/Group Description	Patients must begin therapy within 31 days of surgery. Chemoradiotherapy = Radiation Therapy Dose: 54.0 Gy with a Boost of 5.4 Gy Temozolomide 90mg/m2/day daily for 42 days. Maintenance consists of 6 treatment cycles of combo chemotherapy with lomustine and temozolomide. Maintenance will begin 4 weeks following radiation. Five days of temozolomide (day 1 - 5) and one dose of lomustine (day 1) followed by 36 days of rest = 1 treatment cycle. lomustine: Capsule temozolomide: Capsule adjuvant therapy radiation therapy
All Cause Mortality
	Surgery, Chemoradiotherapy, Rest, Maintenance, FUP
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Surgery, Chemoradiotherapy, Rest, Maintenance, FUP
	Affected / at Risk (%)	# Events
Total	3/106 (2.8%)
Investigations
Neutrophil count decreased	1/106 (0.9%)	1
White blood cell decreased	1/106 (0.9%)	1
Metabolism and nutrition disorders
Anorexia	1/106 (0.9%)	1
Other (Not Including Serious) Adverse Events
	Surgery, Chemoradiotherapy, Rest, Maintenance, FUP
	Affected / at Risk (%)	# Events
Total	83/106 (78.3%)
Blood and lymphatic system disorders
Anemia	26/106 (24.5%)	26
Febrile neutropenia	5/106 (4.7%)	5
Hemolysis	1/106 (0.9%)	1
Endocrine disorders
Cushingoid	1/106 (0.9%)	1
Endocrine disorders - Other, specify	1/106 (0.9%)	1
Eye disorders
Extraocular muscle paresis	1/106 (0.9%)	1
Eye disorders - Other, specify	1/106 (0.9%)	1
Papilledema	1/106 (0.9%)	1
Gastrointestinal disorders
Abdominal pain	1/106 (0.9%)	1
Constipation	1/106 (0.9%)	1
Diarrhea	1/106 (0.9%)	1
Dysphagia	2/106 (1.9%)	2
Intra-abdominal hemorrhage	1/106 (0.9%)	1
Nausea	10/106 (9.4%)	10
Oral pain	1/106 (0.9%)	1
Vomiting	10/106 (9.4%)	10
General disorders
Edema limbs	1/106 (0.9%)	1
Fatigue	6/106 (5.7%)	6
Fever	1/106 (0.9%)	1
Gait disturbance	1/106 (0.9%)	1
Immune system disorders
Allergic reaction	2/106 (1.9%)	2
Infections and infestations
Anorectal infection	1/106 (0.9%)	1
Appendicitis	1/106 (0.9%)	1
Catheter related infection	1/106 (0.9%)	1
Gum infection	1/106 (0.9%)	1
Infections and infestations - Other, specify	5/106 (4.7%)	5
Meningitis	1/106 (0.9%)	1
Skin infection	2/106 (1.9%)	2
Upper respiratory infection	1/106 (0.9%)	1
Urinary tract infection	2/106 (1.9%)	2
Injury, poisoning and procedural complications
Burn	1/106 (0.9%)	1
Radiation recall reaction (dermatologic)	1/106 (0.9%)	1
Investigations
Alanine aminotransferase increased	4/106 (3.8%)	4
Alkaline phosphatase increased	1/106 (0.9%)	1
Aspartate aminotransferase increased	3/106 (2.8%)	3
Blood bilirubin increased	4/106 (3.8%)	4
GGT increased	2/106 (1.9%)	2
Investigations - Other, specify	1/106 (0.9%)	1
Lymphocyte count decreased	36/106 (34%)	36
Neutrophil count decreased	59/106 (55.7%)	59
Platelet count decreased	56/106 (52.8%)	56
Weight loss	1/106 (0.9%)	1
White blood cell decreased	48/106 (45.3%)	48
Metabolism and nutrition disorders
Anorexia	1/106 (0.9%)	1
Dehydration	2/106 (1.9%)	2
Glucose intolerance	1/106 (0.9%)	1
Hyperglycemia	1/106 (0.9%)	1
Hypoalbuminemia	1/106 (0.9%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/106 (1.9%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	1/106 (0.9%)	1
Nervous system disorders
Abducens nerve disorder	1/106 (0.9%)	1
Ataxia	1/106 (0.9%)	1
Depressed level of consciousness	7/106 (6.6%)	7
Dysphasia	3/106 (2.8%)	3
Headache	5/106 (4.7%)	5
Hydrocephalus	3/106 (2.8%)	3
IVth nerve disorder	1/106 (0.9%)	1
Memory impairment	3/106 (2.8%)	3
Nervous system disorders - Other, specify	3/106 (2.8%)	3
Oculomotor nerve disorder	1/106 (0.9%)	1
Peripheral motor neuropathy	5/106 (4.7%)	5
Peripheral sensory neuropathy	3/106 (2.8%)	3
Seizure	8/106 (7.5%)	8
Syncope	1/106 (0.9%)	1
Psychiatric disorders
Depression	2/106 (1.9%)	2
Personality change	1/106 (0.9%)	1
Psychosis	1/106 (0.9%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/106 (0.9%)	1
Hypoxia	2/106 (1.9%)	2
Skin and subcutaneous tissue disorders
Alopecia	1/106 (0.9%)	1
Erythema multiforme	1/106 (0.9%)	1
Rash maculo-papular	3/106 (2.8%)	3
Vascular disorders
Thromboembolic event	2/106 (1.9%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Must obtain prior Sponsor approval.