Radiation Therapy With or Without Temozolomide in Treating Older Patients With Newly Diagnosed Glioblastoma Multiforme

• Sponsor: Canadian Cancer Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00482677
• Collaborator: European Organisation for Research and Treatment of Cancer - EORTC (Other), Trans Tasman Radiation Oncology Group (Other)
• Enrollment: 562
• Locations: 22
• Arms: 2
• Actual Duration (Months): 111.3
• Patients Per Site: 25.5
• Patients Per Site Per Month: 0.2

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, 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 may kill more tumor cells. It is not yet known whether radiation therapy and temozolomide are more effective than radiation therapy alone in treating glioblastoma multiforme.

PURPOSE: This randomized phase III trial is studying radiation therapy and temozolomide to see how well they work compared with radiation therapy alone in treating patients with newly diagnosed glioblastoma multiforme.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: temozolomide; Genetic: DNA methylation analysis; Procedure: quality-of-life assessment; Radiation: Radiation	Phase 3

Detailed Description

OBJECTIVES:

Primary

• Compare overall survival rates in older patients with newly diagnosed glioblastoma multiforme treated with short-course radiotherapy with or without temozolomide.

Secondary

• Compare progression-free survival of patients treated with these regimens.

• Compare the nature, severity, and frequency of adverse events in patients treated with these regimens.

• Compare the quality of life of patient treated with these regimens.

• Determine the methylation status of the O6-methylguanine-DNA methyltransferase promoter.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to center, age (65-70 years vs 71-75 years vs ≥ 76 years), ECOG performance status (0-1 vs 2), and extent of resection at surgery (biopsy only vs complete or incomplete resection). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy once daily on days 1-5, 8-12, and 15-19 in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients undergo radiotherapy as in arm I and receive oral temozolomide once daily on days 1-25.

Beginning 4 weeks after completion of radiotherapy and temozolomide, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with temozolomide alone repeats every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity.

Patients complete quality of life questionnaires at baseline and periodically during study treatment.

Tissue samples are collected at baseline and analyzed for methylation status of the O6-methylguanine-DNA methyltransferase promoter.

After completion of study treatment, patients are followed every 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 562 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase III Study of Temozolomide and Short-Course Radiation Versus Short-Course Radiation Alone In The Treatment of Newly Diagnosed Glioblastoma Multiforme in Elderly Patients
• Actual Study Start Date: May 1, 2007
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Aug 10, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Temozolomide Temozolomide and short course radiation	Drug: temozolomide; Temozolomide (concurrent with radiation) 75 mg/m2 PO 3 weeks once a day, daily, from the first day to the last day of radiotherapy, but for no longer than 28 days, and then adjuvantly for up to 12 cycles (150 mg/m2 for the first 5 days of each cycle). Adjuvant TMZ may be escalated to 200mg/m2 in C2 onward if appropriate.; Genetic: DNA methylation analysis; A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms; Procedure: quality-of-life assessment; prior to randomization until end of study
Active Comparator: Radiation Short course radiation alone	Genetic: DNA methylation analysis; A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms; Procedure: quality-of-life assessment; prior to randomization until end of study; Radiation: Radiation; Short course radiotherapy

Outcome Measures

Primary Outcome Measures

1. Overall Survival [7 years]

   Time from date of randomization to the date of death of any causes, or censored at last known alive date.

Secondary Outcome Measures

1. Progression-free Survival [7 years]

   Time from date of randomization to the date of disease progression or death whichever came first, or censored at last disease assessment date.

2. Adverse Events [7 years]

   Evaluated according to CTCAE V3.0

3. Methylation Status of the O6-methylguanine-DNA Methyltransferase Promoter [7 years]

   Overall survival for patients by Methylation status of the O6-methylguanine-DNA methyltransferase promoter

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histopathologically confirmed glioblastoma multiforme

• Grade IV disease by WHO classification

• Newly diagnosed disease

• Initial diagnostic surgery or biopsy performed within the past 4 weeks

• Not a candidate for standard radiotherapy (60Gy/30 fractions over 6 weeks) in combination with temozolomide

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Absolute granulocyte count ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

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

• Bilirubin ≤ 1.5 times ULN

• ALT and AST < 2.5 times ULN

• No known hypersensitivity to temozolomide or compounds with similar chemical composition to temozolomide

• No history of other malignancies except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other curatively treated solid tumors with no evidence of disease for at least 5 years

• No serious active infection (e.g., wound infection requiring parenteral antibiotics) or other serious underlying medical conditions that would preclude study treatment

• No other condition (e.g., psychological or geographical) that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy

• No prior radiotherapy

• No prior or concurrent investigational therapy

• No concurrent surgical procedures for tumor debulking

• No concurrent stereotactic boost radiotherapy

• No other concurrent chemotherapy, immunotherapy, or biological therapy

• No concurrent epoetin alfa

• Concurrent corticosteroids allowed provided the patient has been on a stable or decreasing dose for at least 14 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
2	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
3	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia	Canada	V3V 1Z2
4	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6
5	BCCA - Vancouver Island Cancer Centre	Victoria	British Columbia	Canada	V8R 6V5
6	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
7	Atlantic Health Sciences Corporation	Saint John	New Brunswick	Canada	E2L 4L2
8	QEII Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 1V7
9	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
10	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
11	Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
12	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
13	CHUM - Hopital Notre-Dame	Montreal	Quebec	Canada	H2L 4M1
14	McGill University - Dept. Oncology	Montreal	Quebec	Canada	H2W 1S6
15	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec	Canada	J1H 5N4
16	Centre hospitalier regional de Trois-Rivieres	Trois-Rivieres	Quebec	Canada	G8Z 3R9
17	Klinikum Der J.W. Goethe Universitaet	Frankfurt		Germany	60590
18	Universitaetsklinikum Freiburg	Freiburg		Germany	79106
19	Universitaetsklinikum Leipzig	Leipzig		Germany	04103
20	Universitaetsklinikum Tuebingen	Tuebingen		Germany	72076
21	Hiroshima University Hospital	Hiroshima		Japan	734-8551
22	Maastro - Maastricht Radiation Oncology	Maastricht		Netherlands	6201

Sponsors and Collaborators

• Canadian Cancer Trials Group
• European Organisation for Research and Treatment of Cancer - EORTC
• Trans Tasman Radiation Oncology Group

Investigators

• Study Chair: Normand Laperriere, MD, FRCPC, Princess Margaret Hospital, Canada
• Study Chair: James R. Perry, MD, FRCPC, Toronto Sunnybrook Regional Cancer Centre
• Study Chair: Alba A. Brandes, MD, Ospedale Bellaria
• Study Chair: Johan Menten, MD, PhD, University Hospital, Gasthuisberg

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Canadian Cancer Trials Group
• ClinicalTrials.gov Identifier: NCT00482677
• Other Study ID Numbers: CE6; CAN-NCIC-CE6; EORTC-26062-22061; TROG 08.02; SPRI-CAN-NCIC-CE.6; CDR0000547163; NCT00493207
• First Posted: Jun 5, 2007
• Last Update Posted: Apr 9, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Canadian Cancer Trials Group: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma
• Additional relevant MeSH terms: Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Temozolomide

Study Results

Participant Flow

Arm/Group Title	Temozolomide	Radiation
Arm/Group Description	Temozolomide and short course radiation temozolomide: Temozolomide (concurrent with radiation) 75 mg/m2 PO 3 weeks once a day, daily, from the first day to the last day of radiotherapy, but for no longer than 28 days, and then adjuvantly for up to 12 cycles (150 mg/m2 for the first 5 days of each cycle). Adjuvant TMZ may be escalated to 200mg/m2 in C2 onward if appropriate. DNA methylation analysis: A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms quality-of-life assessment: prior to randomization until end of study	Short course radiation alone DNA methylation analysis: A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms quality-of-life assessment: prior to randomization until end of study Radiation: Short course radiotherapy
Period Title: Overall Study
STARTED	281	281
COMPLETED	281	281
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Temozolomide	Radiation	Total
Arm/Group Description	Temozolomide and short course radiation temozolomide: Temozolomide (concurrent with radiation) 75 mg/m2 PO 3 weeks once a day, daily, from the first day to the last day of radiotherapy, but for no longer than 28 days, and then adjuvantly for up to 12 cycles (150 mg/m2 for the first 5 days of each cycle). Adjuvant TMZ may be escalated to 200mg/m2 in C2 onward if appropriate. DNA methylation analysis: A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms quality-of-life assessment: prior to randomization until end of study	Short course radiation alone DNA methylation analysis: A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms quality-of-life assessment: prior to randomization until end of study Radiation: Short course radiotherapy	Total of all reporting groups
Overall Participants	281	281	562
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	73	73	73
Sex: Female, Male (Count of Participants)
Female	110 39.1%	109 38.8%	219 39%
Male	171 60.9%	172 61.2%	343 61%
Region of Enrollment (participants) [Number]
Canada	101 35.9%	98 34.9%	199 35.4%
Netherlands	48 17.1%	49 17.4%	97 17.3%
Japan	8 2.8%	9 3.2%	17 3%
Germany	124 44.1%	125 44.5%	249 44.3%
ECOG Performance Status (Count of Participants)
0, 1	215 76.5%	217 77.2%	432 76.9%
2	66 23.5%	64 22.8%	130 23.1%
Resection (Count of Participants)
Biopsy only	84 29.9%	82 29.2%	166 29.5%
Complete/incomplete resection	197 70.1%	199 70.8%	396 70.5%
Mini Mental Status Examination (participants) [Median (Full Range) ]
Median (Full Range) [participants]	27 9.6%	27 9.6%	27 4.8%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Time from date of randomization to the date of death of any causes, or censored at last known alive date.
Time Frame	7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Temozolomide	Radiation
Arm/Group Description	Temozolomide and short course radiation temozolomide: Temozolomide (concurrent with radiation) 75 mg/m2 PO 3 weeks once a day, daily, from the first day to the last day of radiotherapy, but for no longer than 28 days, and then adjuvantly for up to 12 cycles (150 mg/m2 for the first 5 days of each cycle). Adjuvant TMZ may be escalated to 200mg/m2 in C2 onward if appropriate. DNA methylation analysis: A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms quality-of-life assessment: prior to randomization until end of study	Short course radiation alone DNA methylation analysis: A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms quality-of-life assessment: prior to randomization until end of study Radiation: Short course radiotherapy
Measure Participants	281	281
Median (95% Confidence Interval) [Months]	9.33	7.62

2. Secondary Outcome

Title	Progression-free Survival
Description	Time from date of randomization to the date of disease progression or death whichever came first, or censored at last disease assessment date.
Time Frame	7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Temozolomide	Radiation
Arm/Group Description	Temozolomide and short course radiation temozolomide: Temozolomide (concurrent with radiation) 75 mg/m2 PO 3 weeks once a day, daily, from the first day to the last day of radiotherapy, but for no longer than 28 days, and then adjuvantly for up to 12 cycles (150 mg/m2 for the first 5 days of each cycle). Adjuvant TMZ may be escalated to 200mg/m2 in C2 onward if appropriate. DNA methylation analysis: A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms quality-of-life assessment: prior to randomization until end of study	Short course radiation alone DNA methylation analysis: A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms quality-of-life assessment: prior to randomization until end of study Radiation: Short course radiotherapy
Measure Participants	281	281
Median (95% Confidence Interval) [Months]	5.29	3.94

3. Secondary Outcome

Title	Adverse Events
Description	Evaluated according to CTCAE V3.0
Time Frame	7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Methylation Status of the O6-methylguanine-DNA Methyltransferase Promoter
Description	Overall survival for patients by Methylation status of the O6-methylguanine-DNA methyltransferase promoter
Time Frame	7 years

Outcome Measure Data

Analysis Population Description

Patients with MGMT promoter methylated.

Arm/Group Title	Temozolomide	Radiation
Arm/Group Description	Temozolomide and short course radiation temozolomide: Temozolomide (concurrent with radiation) 75 mg/m2 PO 3 weeks once a day, daily, from the first day to the last day of radiotherapy, but for no longer than 28 days, and then adjuvantly for up to 12 cycles (150 mg/m2 for the first 5 days of each cycle). Adjuvant TMZ may be escalated to 200mg/m2 in C2 onward if appropriate. DNA methylation analysis: A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms quality-of-life assessment: prior to randomization until end of study	Short course radiation alone DNA methylation analysis: A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms quality-of-life assessment: prior to randomization until end of study Radiation: Short course radiotherapy
Measure Participants	88	77
Median (95% Confidence Interval) [Months]	13.47	7.69

Adverse Events

Arm/Group Title	Temozolomide		Radiation
Arm/Group Description	Temozolomide and short course radiation temozolomide: Temozolomide (concurrent with radiation) 75 mg/m2 PO 3 weeks once a day, daily, from the first day to the last day of radiotherapy, but for no longer than 28 days, and then adjuvantly for up to 12 cycles (150 mg/m2 for the first 5 days of each cycle). Adjuvant TMZ may be escalated to 200mg/m2 in C2 onward if appropriate. DNA methylation analysis: A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms quality-of-life assessment: prior to randomization until end of study		Short course radiation alone DNA methylation analysis: A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms quality-of-life assessment: prior to randomization until end of study Radiation: Short course radiotherapy
All Cause Mortality
	Temozolomide		Radiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Temozolomide		Radiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	158/271 (58.3%)		135/271 (49.8%)
Blood and lymphatic system disorders
Febrile neutropenia	5/271 (1.8%)		1/271 (0.4%)
Hemoglobin	0/271 (0%)		1/271 (0.4%)
Cardiac disorders
Cardiac ischemia/infarction	1/271 (0.4%)		2/271 (0.7%)
Cardiopulmonary arrest	2/271 (0.7%)		0/271 (0%)
Left ventricular systolic dysfunction	1/271 (0.4%)		0/271 (0%)
Pain Cardiac/heart	1/271 (0.4%)		0/271 (0%)
Supraventricular arrhythmia Atrial fibrillation	2/271 (0.7%)		1/271 (0.4%)
Ventricular arrhythmia Ventricular tachycardia	1/271 (0.4%)		0/271 (0%)
Eye disorders
Blurred vision	2/271 (0.7%)		1/271 (0.4%)
Glaucoma	1/271 (0.4%)		0/271 (0%)
Neuropathy: cranial CN II	2/271 (0.7%)		3/271 (1.1%)
Pain Eye	0/271 (0%)		1/271 (0.4%)
Gastrointestinal disorders
Constipation	2/271 (0.7%)		2/271 (0.7%)
Diarrhea	1/271 (0.4%)		0/271 (0%)
Dysphagia	7/271 (2.6%)		5/271 (1.8%)
Hemorrhage, GI Lower GI NOS	1/271 (0.4%)		0/271 (0%)
Hemorrhage, GI Rectum	0/271 (0%)		1/271 (0.4%)
Ileus	1/271 (0.4%)		0/271 (0%)
Incontinence, anal	0/271 (0%)		2/271 (0.7%)
Nausea	2/271 (0.7%)		1/271 (0.4%)
Pain Abdomen NOS	2/271 (0.7%)		1/271 (0.4%)
Pancreatitis	2/271 (0.7%)		0/271 (0%)
Perforation, GI Colon	2/271 (0.7%)		1/271 (0.4%)
Perforation, GI Esophagus	1/271 (0.4%)		0/271 (0%)
Ulcer, GI Stomach	0/271 (0%)		1/271 (0.4%)
Vomiting	4/271 (1.5%)		2/271 (0.7%)
General disorders
Constitutional Symptoms - Other	1/271 (0.4%)		1/271 (0.4%)
Death Death NOS	7/271 (2.6%)		7/271 (2.6%)
Death Disease progression NOS	1/271 (0.4%)		3/271 (1.1%)
Edema: head and neck	1/271 (0.4%)		3/271 (1.1%)
Edema: limb	1/271 (0.4%)		1/271 (0.4%)
Fatigue	17/271 (6.3%)		16/271 (5.9%)
Fever	5/271 (1.8%)		3/271 (1.1%)
Gait/walking	1/271 (0.4%)		1/271 (0.4%)
Pain Pain NOS	0/271 (0%)		1/271 (0.4%)
Syndromes - Other	1/271 (0.4%)		0/271 (0%)
Hepatobiliary disorders
Cholecystitis	1/271 (0.4%)		0/271 (0%)
Infections and infestations
Infection (documented clinically) Colon	1/271 (0.4%)		0/271 (0%)
Infection (documented clinically) Lung	2/271 (0.7%)		4/271 (1.5%)
Infection (documented clinically) Muscle	1/271 (0.4%)		0/271 (0%)
Infection (documented clinically) Peritoneal cavity	1/271 (0.4%)		0/271 (0%)
Infection - Other	2/271 (0.7%)		2/271 (0.7%)
Infection with normal ANC Abdomen NOS	1/271 (0.4%)		0/271 (0%)
Infection with normal ANC Bladder	0/271 (0%)		1/271 (0.4%)
Infection with normal ANC Blood	4/271 (1.5%)		0/271 (0%)
Infection with normal ANC Brain	1/271 (0.4%)		0/271 (0%)
Infection with normal ANC Colon	1/271 (0.4%)		0/271 (0%)
Infection with normal ANC Lung	6/271 (2.2%)		2/271 (0.7%)
Infection with normal ANC Peritoneal cavity	1/271 (0.4%)		0/271 (0%)
Infection with normal ANC Skin	0/271 (0%)		1/271 (0.4%)
Infection with normal ANC Soft tissue NOS	0/271 (0%)		1/271 (0.4%)
Infection with normal ANC Upper airway NOS	0/271 (0%)		1/271 (0.4%)
Infection with normal ANC Urinary tract NOS	1/271 (0.4%)		1/271 (0.4%)
Infection with normal ANC Wound	1/271 (0.4%)		1/271 (0.4%)
Infection with unknown ANC Blood	1/271 (0.4%)		0/271 (0%)
Infection with unknown ANC Bronchus	1/271 (0.4%)		0/271 (0%)
Infection with unknown ANC Lung	1/271 (0.4%)		3/271 (1.1%)
Infection with unknown ANC Skin	0/271 (0%)		1/271 (0.4%)
Infection with unknown ANC Urinary tract NOS	1/271 (0.4%)		0/271 (0%)
Injury, poisoning and procedural complications
Dermatitis Radiation	0/271 (0%)		1/271 (0.4%)
Fracture	6/271 (2.2%)		7/271 (2.6%)
Thrombosis/embolism (vascular access)	3/271 (1.1%)		2/271 (0.7%)
Wound complication, non-infectious	1/271 (0.4%)		0/271 (0%)
Investigations
ADH	0/271 (0%)		1/271 (0.4%)
GGT	1/271 (0.4%)		0/271 (0%)
Platelets	4/271 (1.5%)		2/271 (0.7%)
Weight loss	0/271 (0%)		1/271 (0.4%)
Metabolism and nutrition disorders
Acidosis	1/271 (0.4%)		0/271 (0%)
Anorexia	4/271 (1.5%)		3/271 (1.1%)
Dehydration	3/271 (1.1%)		2/271 (0.7%)
Diabetes	2/271 (0.7%)		1/271 (0.4%)
Hyperglycemia	2/271 (0.7%)		2/271 (0.7%)
Hypernatremia	0/271 (0%)		1/271 (0.4%)
Hypokalemia	0/271 (0%)		1/271 (0.4%)
Musculoskeletal and connective tissue disorders
Joint-function	1/271 (0.4%)		0/271 (0%)
Muscle weakness Extremity-lower	8/271 (3%)		2/271 (0.7%)
Muscle weakness Extremity-upper	2/271 (0.7%)		1/271 (0.4%)
Muscle weakness Left-sided	3/271 (1.1%)		4/271 (1.5%)
Muscle weakness Right-sided	3/271 (1.1%)		2/271 (0.7%)
Muscle weakness Whole body/generalized	5/271 (1.8%)		5/271 (1.8%)
Pain Back	3/271 (1.1%)		1/271 (0.4%)
Pain Bone	0/271 (0%)		2/271 (0.7%)
Pain Extremity-limb	1/271 (0.4%)		0/271 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain Tumor pain	0/271 (0%)		1/271 (0.4%)
Nervous system disorders
Arachnoiditis	1/271 (0.4%)		0/271 (0%)
Ataxia	6/271 (2.2%)		6/271 (2.2%)
CNS hemorrhage	2/271 (0.7%)		2/271 (0.7%)
CNS ischemia	5/271 (1.8%)		2/271 (0.7%)
CNS necrosis	0/271 (0%)		1/271 (0.4%)
CSF leak	1/271 (0.4%)		0/271 (0%)
Cognitive disturbance	16/271 (5.9%)		11/271 (4.1%)
Dizziness	1/271 (0.4%)		1/271 (0.4%)
Encephalopathy	0/271 (0%)		1/271 (0.4%)
Hydrocephalus	3/271 (1.1%)		0/271 (0%)
Involuntary movement	0/271 (0%)		1/271 (0.4%)
Memory impairment	1/271 (0.4%)		3/271 (1.1%)
Neurology - Other	2/271 (0.7%)		3/271 (1.1%)
Neuropathy-motor	29/271 (10.7%)		22/271 (8.1%)
Neuropathy-sensory	1/271 (0.4%)		3/271 (1.1%)
Neuropathy: cranial CN III	1/271 (0.4%)		0/271 (0%)
Neuropathy: cranial CN VII	1/271 (0.4%)		0/271 (0%)
Neuropathy: cranial CN VIII	0/271 (0%)		1/271 (0.4%)
Pain Head/headache	5/271 (1.8%)		7/271 (2.6%)
Pyramidal tract dysfunction	1/271 (0.4%)		1/271 (0.4%)
Seizure	27/271 (10%)		20/271 (7.4%)
Somnolence	11/271 (4.1%)		20/271 (7.4%)
Speech impairment	16/271 (5.9%)		21/271 (7.7%)
Syncope	1/271 (0.4%)		3/271 (1.1%)
Psychiatric disorders
Confusion	17/271 (6.3%)		23/271 (8.5%)
Mood alteration Agitation	7/271 (2.6%)		3/271 (1.1%)
Mood alteration Anxiety	1/271 (0.4%)		1/271 (0.4%)
Mood alteration Depression	4/271 (1.5%)		1/271 (0.4%)
Personality	0/271 (0%)		2/271 (0.7%)
Psychosis	0/271 (0%)		1/271 (0.4%)
Renal and urinary disorders
Cystitis	0/271 (0%)		1/271 (0.4%)
Hemorrhage, GU Kidney	1/271 (0.4%)		0/271 (0%)
Incontinence, urinary	0/271 (0%)		2/271 (0.7%)
Renal failure	1/271 (0.4%)		1/271 (0.4%)
Urinary retention	1/271 (0.4%)		0/271 (0%)
Reproductive system and breast disorders
Hemorrhage, GU Prostate	0/271 (0%)		1/271 (0.4%)
Respiratory, thoracic and mediastinal disorders
Aspiration	2/271 (0.7%)		3/271 (1.1%)
Cough	1/271 (0.4%)		0/271 (0%)
Dyspnea	2/271 (0.7%)		6/271 (2.2%)
Hemorrhage pulmonary Nose	2/271 (0.7%)		0/271 (0%)
Hypoxia	1/271 (0.4%)		0/271 (0%)
Pleural effusion	1/271 (0.4%)		0/271 (0%)
Pneumonitis	4/271 (1.5%)		5/271 (1.8%)
Pneumothorax	1/271 (0.4%)		1/271 (0.4%)
Pulmonary - Other	2/271 (0.7%)		1/271 (0.4%)
Pulmonary hypertension	1/271 (0.4%)		0/271 (0%)
Skin and subcutaneous tissue disorders
Decubitus	1/271 (0.4%)		0/271 (0%)
Dermatology - Other	0/271 (0%)		1/271 (0.4%)
Erythema multiforme	0/271 (0%)		1/271 (0.4%)
Petechiae	1/271 (0.4%)		0/271 (0%)
Rash	1/271 (0.4%)		1/271 (0.4%)
Ulceration	1/271 (0.4%)		0/271 (0%)
Vascular disorders
Hematoma	0/271 (0%)		1/271 (0.4%)
Hypertension	1/271 (0.4%)		0/271 (0%)
Hypotension	2/271 (0.7%)		0/271 (0%)
Phlebitis	1/271 (0.4%)		0/271 (0%)
Thrombosis/thrombus/embolism	25/271 (9.2%)		10/271 (3.7%)
Other (Not Including Serious) Adverse Events
	Temozolomide		Radiation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	260/271 (95.9%)		256/271 (94.5%)
Ear and labyrinth disorders
Hearing (without monitoring program)	15/271 (5.5%)		14/271 (5.2%)
Eye disorders
Blurred vision	15/271 (5.5%)		21/271 (7.7%)
Gastrointestinal disorders
Constipation	74/271 (27.3%)		29/271 (10.7%)
Diarrhea	19/271 (7%)		5/271 (1.8%)
Dysphagia	20/271 (7.4%)		18/271 (6.6%)
Nausea	77/271 (28.4%)		42/271 (15.5%)
Vomiting	38/271 (14%)		15/271 (5.5%)
General disorders
Edema: limb	50/271 (18.5%)		35/271 (12.9%)
Fatigue	158/271 (58.3%)		147/271 (54.2%)
Gait/walking	22/271 (8.1%)		19/271 (7%)
Injury, poisoning and procedural complications
Dermatitis Radiation	22/271 (8.1%)		22/271 (8.1%)
Metabolism and nutrition disorders
Anorexia	41/271 (15.1%)		38/271 (14%)
Musculoskeletal and connective tissue disorders
Muscle weakness Extremity-lower	42/271 (15.5%)		34/271 (12.5%)
Muscle weakness Whole body/generalized	17/271 (6.3%)		18/271 (6.6%)
Pain Muscle	16/271 (5.9%)		8/271 (3%)
Nervous system disorders
Ataxia	30/271 (11.1%)		29/271 (10.7%)
Cognitive disturbance	55/271 (20.3%)		46/271 (17%)
Dizziness	43/271 (15.9%)		25/271 (9.2%)
Memory impairment	66/271 (24.4%)		64/271 (23.6%)
Neurology - Other	19/271 (7%)		16/271 (5.9%)
Neuropathy-motor	77/271 (28.4%)		65/271 (24%)
Neuropathy-sensory	24/271 (8.9%)		15/271 (5.5%)
Pain Head/headache	64/271 (23.6%)		78/271 (28.8%)
Seizure	73/271 (26.9%)		57/271 (21%)
Somnolence	24/271 (8.9%)		39/271 (14.4%)
Speech impairment	68/271 (25.1%)		77/271 (28.4%)
Tremor	18/271 (6.6%)		16/271 (5.9%)
Psychiatric disorders
Confusion	66/271 (24.4%)		65/271 (24%)
Insomnia	31/271 (11.4%)		31/271 (11.4%)
Mood alteration Agitation	26/271 (9.6%)		16/271 (5.9%)
Mood alteration Anxiety	19/271 (7%)		12/271 (4.4%)
Mood alteration Depression	37/271 (13.7%)		20/271 (7.4%)
Renal and urinary disorders
Incontinence, urinary	22/271 (8.1%)		17/271 (6.3%)
Urinary frequency	19/271 (7%)		16/271 (5.9%)
Respiratory, thoracic and mediastinal disorders
Cough	23/271 (8.5%)		27/271 (10%)
Dyspnea	30/271 (11.1%)		25/271 (9.2%)
Skin and subcutaneous tissue disorders
Alopecia	69/271 (25.5%)		77/271 (28.4%)
Pruritus	17/271 (6.3%)		8/271 (3%)
Rash	29/271 (10.7%)		19/271 (7%)
Vascular disorders
Thrombosis/thrombus/embolism	34/271 (12.5%)		23/271 (8.5%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

All Principal Investigators ARE 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.