Trial Outcomes & Findings for Temozolomide and Radiation Therapy With or Without Cediranib Maleate in Treating Patients With Newly Diagnosed Glioblastoma (NCT NCT01062425)

Last Updated: 2022-07-26

Results Overview

Six-month progression-free survival is the rate of patients who have NOT progressed at six months, where progressive disease is defined as any of the following: ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration. Progression will be determined by central review of MRI exams, assessed using MacDonald criteria for progression versus response on 2D T1 and T2 weighted images.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

261 participants

Primary outcome timeframe

From randomization to 6 months.

Results posted on

2022-07-26

Participant Flow

After patient registration, sites submitted tissue for central histology and methyltransferase (MGMT) gene methylation evaluation. If tissue was evaluable and a patient continued on study, then treatment arm was assigned. Two hundred sixty-one patients were registered, 103 did not continue to treatment assignment, 158 had treatment assigned.

Participant milestones

Participant milestones
Measure	Placebo, TMZ, and RT Placebo (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + placebo followed by placebo monotherapy (4 weeks) followed by TMZ + placebo for 12 cycle maximum	Cediranib, TMZ, and RT Cediranib (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + cediranib followed by cediranib monotherapy (4 weeks) followed by TMZ + cediranib for 12 cycle maximum
Overall Study STARTED	55	103
Overall Study COMPLETED	52	97
Overall Study NOT COMPLETED	3	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo, TMZ, and RT Placebo (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + placebo followed by placebo monotherapy (4 weeks) followed by TMZ + placebo for 12 cycle maximum	Cediranib, TMZ, and RT Cediranib (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + cediranib followed by cediranib monotherapy (4 weeks) followed by TMZ + cediranib for 12 cycle maximum
Overall Study Protocol Violation	3	6

Baseline Characteristics

Temozolomide and Radiation Therapy With or Without Cediranib Maleate in Treating Patients With Newly Diagnosed Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo, TMZ, and RT n=52 Participants Placebo (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + placebo followed by placebo monotherapy (4 weeks) followed by TMZ + placebo for 12 cycle maximum	Cediranib, TMZ, and RT n=97 Participants Cediranib (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + cediranib followed by cediranib monotherapy (4 weeks) followed by TMZ + cediranib for 12 cycle maximum	Total n=149 Participants Total of all reporting groups
Age, Continuous	59 years n=5 Participants	61 years n=7 Participants	60 years n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	44 Participants n=7 Participants	68 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	53 Participants n=7 Participants	81 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to 6 months.

Population: Randomized eligible patients with evaluable data at six months. (From the randomized eligible patients, 2 patients withdrew prior to 6 months and 1 did not have an evaluable scan on the placebo arm, while 4 withdrew before 6 months, 3 did not have an evaluable scan, and 2 did not receive protocol treatment on the cediranib arm.)

Outcome measures

Outcome measures
Measure	Placebo, TMZ, and RT n=49 Participants Placebo (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + placebo followed by placebo monotherapy (4 weeks) followed by TMZ + placebo for 12 cycle maximum	Cediranib, TMZ, and RT n=88 Participants Cediranib (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + cediranib followed by cediranib monotherapy (4 weeks) followed by TMZ + cediranib for 12 cycle maximum
6-month Progression-free Survival Rate	24.5 percentage of participants Interval 12.5 to 36.5	46.6 percentage of participants Interval 36.2 to 57.0

SECONDARY outcome

Timeframe: From randomization to time of death due to any cause. Patients are followed until death. Analysis occurs after all patients have been potentially followed for six months.

Population: All randomized and eligible patients.

OS will be estimated using the Kaplan-Meier method and differences between treatment arms will be tested using the log rank test. Multivariate analyses with the Cox proportional hazard model for OS will be performed with the stratification variables as fixed variables to assess the treatment effect adjusting patient-specific risk factors.

Outcome measures

Outcome measures
Measure	Placebo, TMZ, and RT n=52 Participants Placebo (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + placebo followed by placebo monotherapy (4 weeks) followed by TMZ + placebo for 12 cycle maximum	Cediranib, TMZ, and RT n=97 Participants Cediranib (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + cediranib followed by cediranib monotherapy (4 weeks) followed by TMZ + cediranib for 12 cycle maximum
Overall Survival (OS)	13.8 Months Interval 9.6 to 18.9	14.5 Months Interval 12.3 to 19.7

SECONDARY outcome

Timeframe: From randomization to time of first progression or death due to any cause. Patients are followed until death. Analysis occurs after all patients have been potentially followed for six months.

Population: All randomized and eligible patients.

Progression-free survival time is defined as time from randomization to date of first progression or death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive without progression are censored at the date of last contact. Progression is defined as any of the following: ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration.

Outcome measures

Outcome measures
Measure	Placebo, TMZ, and RT n=52 Participants Placebo (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + placebo followed by placebo monotherapy (4 weeks) followed by TMZ + placebo for 12 cycle maximum	Cediranib, TMZ, and RT n=97 Participants Cediranib (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + cediranib followed by cediranib monotherapy (4 weeks) followed by TMZ + cediranib for 12 cycle maximum
Progression-free Survival (PFS)	2.7 Months Interval 2.5 to 3.7	6.2 Months Interval 4.5 to 8.1

SECONDARY outcome

Timeframe: From randomization to six months.

Population: All randomized and eligible patients who started protocol treatment.

The number of patients with reported grade 3 and higher treatment-related toxicities as assessed by Common Terminology Criteria for Adverse Events version 4.0

Outcome measures

Outcome measures
Measure	Placebo, TMZ, and RT n=52 Participants Placebo (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + placebo followed by placebo monotherapy (4 weeks) followed by TMZ + placebo for 12 cycle maximum	Cediranib, TMZ, and RT n=92 Participants Cediranib (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + cediranib followed by cediranib monotherapy (4 weeks) followed by TMZ + cediranib for 12 cycle maximum
Incidence of Grade 3+ Toxicities	35 participants	77 participants

Adverse Events

Placebo, TMZ, and RT

Serious events: 23 serious events

Other events: 49 other events

Deaths: 0 deaths

Cediranib, TMZ, and RT

Serious events: 53 serious events

Other events: 88 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld, M.S.

NRG Oncology

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Placebo, TMZ, and RT n=52 participants at risk Placebo (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + placebo followed by placebo monotherapy (4 weeks) followed by TMZ + placebo for 12 cycle maximum	Cediranib, TMZ, and RT n=92 participants at risk Cediranib (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + cediranib followed by cediranib monotherapy (4 weeks) followed by TMZ + cediranib for 12 cycle maximum
Blood and lymphatic system disorders Anemia	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	4.3% 4/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Blood and lymphatic system disorders Bone marrow hypocellular	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	2.2% 2/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Blood and lymphatic system disorders Febrile neutropenia	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Blood and lymphatic system disorders Leukocytosis	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	0.00% 0/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Cardiac disorders Atrial fibrillation	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Endocrine disorders Hypothyroidism	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Eye disorders Blurred vision	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Constipation	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Diarrhea	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	6.5% 6/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Dry mouth	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Hemorrhoidal hemorrhage	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Nausea	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	4.3% 4/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Pancreatitis	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Retroperitoneal hemorrhage	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	0.00% 0/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Vomiting	3.8% 2/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	2.2% 2/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Chills	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Death NOS	3.8% 2/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Edema limbs	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	2.2% 2/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Fatigue	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	6.5% 6/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Fever	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	2.2% 2/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Gait disturbance	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	0.00% 0/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Non-cardiac chest pain	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Abdominal infection	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Bladder infection	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Encephalomyelitis infection	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Infections and infestations - Other	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Lung infection	3.8% 2/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Mucosal infection	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Sepsis	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	2.2% 2/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Soft tissue infection	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Tooth infection	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	0.00% 0/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Urinary tract infection	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	0.00% 0/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Wound infection	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	0.00% 0/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Injury, poisoning and procedural complications Dermatitis radiation	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	0.00% 0/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Injury, poisoning and procedural complications Fall	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	0.00% 0/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Injury, poisoning and procedural complications Postoperative hemorrhage	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Investigations Alanine aminotransferase increased	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	2.2% 2/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Investigations Aspartate aminotransferase increased	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Investigations Creatinine increased	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	1.1% 1/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.

Other adverse events
Measure	Placebo, TMZ, and RT n=52 participants at risk Placebo (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + placebo followed by placebo monotherapy (4 weeks) followed by TMZ + placebo for 12 cycle maximum	Cediranib, TMZ, and RT n=92 participants at risk Cediranib (3 days) followed by radiation therapy (RT) + daily temozolomide (TMZ) + cediranib followed by cediranib monotherapy (4 weeks) followed by TMZ + cediranib for 12 cycle maximum
Blood and lymphatic system disorders Anemia	38.5% 20/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	29.3% 27/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	9.6% 5/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	4.3% 4/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Ear and labyrinth disorders Ear pain	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	2.2% 2/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Ear and labyrinth disorders Hearing impaired	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	2.2% 2/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Ear and labyrinth disorders Tinnitus	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	6.5% 6/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Endocrine disorders Hypothyroidism	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	6.5% 6/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Eye disorders Blurred vision	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	14.1% 13/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Eye disorders Eye disorders - Other	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	5.4% 5/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Abdominal pain	3.8% 2/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	19.6% 18/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Constipation	46.2% 24/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	44.6% 41/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Diarrhea	15.4% 8/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	57.6% 53/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Dry mouth	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	6.5% 6/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Dyspepsia	7.7% 4/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	7.6% 7/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Dysphagia	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	7.6% 7/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Gastroesophageal reflux disease	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	6.5% 6/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Mucositis oral	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	6.5% 6/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Nausea	38.5% 20/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	64.1% 59/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Gastrointestinal disorders Vomiting	7.7% 4/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	32.6% 30/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Chills	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	6.5% 6/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Edema face	11.5% 6/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	3.3% 3/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Edema limbs	9.6% 5/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	7.6% 7/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Fatigue	78.8% 41/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	83.7% 77/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Fever	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	7.6% 7/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Gait disturbance	15.4% 8/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	8.7% 8/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Malaise	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	5.4% 5/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
General disorders Pain	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	6.5% 6/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Mucosal infection	7.7% 4/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	9.8% 9/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Infections and infestations Urinary tract infection	9.6% 5/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	6.5% 6/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Injury, poisoning and procedural complications Bruising	0.00% 0/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	7.6% 7/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Injury, poisoning and procedural complications Dermatitis radiation	19.2% 10/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	16.3% 15/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Injury, poisoning and procedural complications Fall	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	5.4% 5/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Investigations Alanine aminotransferase increased	26.9% 14/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	44.6% 41/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Investigations Alkaline phosphatase increased	3.8% 2/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	8.7% 8/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Investigations Aspartate aminotransferase increased	11.5% 6/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	27.2% 25/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Investigations Blood bilirubin increased	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	10.9% 10/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Investigations CD4 lymphocytes decreased	5.8% 3/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	3.3% 3/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Investigations Creatinine increased	9.6% 5/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	17.4% 16/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Investigations Hemoglobin increased	1.9% 1/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	6.5% 6/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Investigations Investigations - Other	19.2% 10/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	22.8% 21/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.
Investigations Lymphocyte count decreased	32.7% 17/52 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.	38.0% 35/92 • Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE). All randomized and eligible patients who started protocol treatment.