Trial Outcomes & Findings for Avastin in Combination With Radiation (XRT) & Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma (GBM) and Gliosarcomas (NCT NCT00597402)

NCT ID: NCT00597402

Last Updated: 2014-05-07

Results Overview

Percentage of participants surviving sixteen months from the start of study treatment. OS was defined as the time from the date of study treatment initiation to the date of death due to any cause.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 125 participants
• Primary outcome timeframe: 16 months
• Results posted on: 2014-05-07

Participant Flow

Participant milestones

Measure	Avastin, Radiation, Temozolomide, and Irinotecan Treatment with standard XRT (radiation) and daily temozolomide 75 mg/m2/day for 6.5 weeks of XRT. Avastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive 6 cycles of Avastin, temozolomide, and irinotecan. Beginning a minimum of 14 days after last XRT, Avastin at 10 mg/kg with irinotecan every other week; temozolomide will be given at 200 mg/m2/day on the 1st 5 days of each 28-day cycle. The irinotecan dose will depend on whether the patient is taking enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED:125 mg/m2.)
Overall Study STARTED	125
Overall Study COMPLETED	125
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Avastin in Combination With Radiation (XRT) & Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma (GBM) and Gliosarcomas

Baseline characteristics by cohort

Measure	Avastin, Radiation, Temozolomide, and Irinotecan n=125 Participants Treatment with standard XRT (radiation) and daily temozolomide 75 mg/m2/day for 6.5 weeks of XRT. Avastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive 6 cycles of Avastin, temozolomide, and irinotecan. Beginning a minimum of 14 days after last XRT, Avastin at 10 mg/kg with irinotecan every other week; temozolomide will be given at 200 mg/m2/day on the 1st 5 days of each 28-day cycle. The irinotecan dose will depend on whether the patient is taking enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED:125 mg/m2.)
Age, Continuous	54.6 years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	51 Participants n=5 Participants
Sex: Female, Male Male	74 Participants n=5 Participants

PRIMARY outcome

Timeframe: 16 months

Population: Intent to treat

Percentage of participants surviving sixteen months from the start of study treatment. OS was defined as the time from the date of study treatment initiation to the date of death due to any cause.

Outcome measures

Measure

Avastin, Radiation, Temozolomide, and Irinotecan n=125 Participants Treatment with standard XRT (radiation) and daily temozolomide 75 mg/m2/day for 6.5 weeks of XRT. Avastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive 6 cycles of Avastin, temozolomide, and irinotecan. Beginning a minimum of 14 days after last XRT, Avastin at 10 mg/kg with irinotecan every other week; temozolomide will be given at 200 mg/m2/day on the 1st 5 days of each 28-day cycle. The irinotecan dose will depend on whether the patient is taking enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED:125 mg/m2.)

16-month Overall Survival (OS)

64.8 percentage of participants Interval 55.7 to 72.5

SECONDARY outcome

Timeframe: 12 months

Percentage of participants surviving twelve months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.

Outcome measures

Measure

Avastin, Radiation, Temozolomide, and Irinotecan n=125 Participants Treatment with standard XRT (radiation) and daily temozolomide 75 mg/m2/day for 6.5 weeks of XRT. Avastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive 6 cycles of Avastin, temozolomide, and irinotecan. Beginning a minimum of 14 days after last XRT, Avastin at 10 mg/kg with irinotecan every other week; temozolomide will be given at 200 mg/m2/day on the 1st 5 days of each 28-day cycle. The irinotecan dose will depend on whether the patient is taking enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED:125 mg/m2.)

12-month Progression-free Survival (PFS)

63.2 percentage of participants Interval 54.1 to 71.0

SECONDARY outcome

Timeframe: 55 months

Number of times a CNS hemorrhage or systemic hemorrhage was experienced

Outcome measures

Measure	Avastin, Radiation, Temozolomide, and Irinotecan n=125 Participants Treatment with standard XRT (radiation) and daily temozolomide 75 mg/m2/day for 6.5 weeks of XRT. Avastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive 6 cycles of Avastin, temozolomide, and irinotecan. Beginning a minimum of 14 days after last XRT, Avastin at 10 mg/kg with irinotecan every other week; temozolomide will be given at 200 mg/m2/day on the 1st 5 days of each 28-day cycle. The irinotecan dose will depend on whether the patient is taking enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED:125 mg/m2.)
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage Gr.2 Central Nervous System (CNS) Hemorrhage	1 participants
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage Gr.3 Central Nervous System (CNS) Hemorrhage	0 participants
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage Gr.4 Central Nervous System (CNS) Hemorrhage	1 participants
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage Gr.5 Central Nervous System (CNS) Hemorrhage	0 participants
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage Gr.2 Systemic Hemorrhage	1 participants
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage Gr.3 Systemic Hemorrhage	0 participants
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage Gr.4 Systemic Hemorrhage	0 participants
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage Gr.5 Systemic Hemorrhage	0 participants

SECONDARY outcome

Timeframe: 55 months

Number of times a grade ≥ 4 hematologic or grade ≥ 3 non-hematologic toxicity was experienced

Outcome measures

Measure	Avastin, Radiation, Temozolomide, and Irinotecan n=125 Participants Treatment with standard XRT (radiation) and daily temozolomide 75 mg/m2/day for 6.5 weeks of XRT. Avastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive 6 cycles of Avastin, temozolomide, and irinotecan. Beginning a minimum of 14 days after last XRT, Avastin at 10 mg/kg with irinotecan every other week; temozolomide will be given at 200 mg/m2/day on the 1st 5 days of each 28-day cycle. The irinotecan dose will depend on whether the patient is taking enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED:125 mg/m2.)
Number of Patients Experiencing a Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity Grade ≥3 Non-hematologic Toxicities	49 participants
Number of Patients Experiencing a Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity Grade ≥ 4 Hematologic Toxicities	20 participants

Adverse Events

Avastin, Radiation, Temozolomide, and Irinotecan

Serious events: 35 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Measure	Avastin, Radiation, Temozolomide, and Irinotecan n=125 participants at risk Treatment with standard XRT (radiation) and daily temozolomide 75 mg/m2/day for 6.5 weeks of XRT. Avastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive 6 cycles of Avastin, temozolomide, and irinotecan. Beginning a minimum of 14 days after last XRT, Avastin at 10 mg/kg with irinotecan every other week; temozolomide will be given at 200 mg/m2/day on the 1st 5 days of each 28-day cycle. The irinotecan dose will depend on whether the patient is taking enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED:125 mg/m2.)
Blood and lymphatic system disorders Anemia	3.2% 4/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Cardiac disorders Atrial fibrillation	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Gastrointestinal disorders Colitis	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Gastrointestinal disorders Hemorrhoids	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
General disorders Death NOS	1.6% 2/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
General disorders Fatigue	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
General disorders Sudden death NOS	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Infections and infestations Bone infection	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Infections and infestations Infections and infestations - Other, specify	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Infections and infestations Infections and infestations - Other, specify: Infecti	1.6% 2/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Infections and infestations Lung infection	2.4% 3/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Infections and infestations Skin infection	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Infections and infestations Urinary tract infection	1.6% 2/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Investigations Neutrophil count decreased	2.4% 3/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Investigations Platelet count decreased	3.2% 4/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Investigations White blood cell decreased	2.4% 3/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Metabolism and nutrition disorders Dehydration	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Metabolism and nutrition disorders Hyperglycemia	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Metabolism and nutrition disorders Hyponatremia	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Nervous system disorders Cerebrospinal fluid leakage	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Nervous system disorders Cognitive disturbance	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Nervous system disorders Headache	1.6% 2/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Nervous system disorders Intracranial hemorrhage	1.6% 2/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Nervous system disorders Peripheral motor neuropathy	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Nervous system disorders Seizure	10.4% 13/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Psychiatric disorders Confusion	4.0% 5/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Psychiatric disorders Psychosis	0.80% 1/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Vascular disorders Thromboembolic event	5.6% 7/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.

Other adverse events

Measure	Avastin, Radiation, Temozolomide, and Irinotecan n=125 participants at risk Treatment with standard XRT (radiation) and daily temozolomide 75 mg/m2/day for 6.5 weeks of XRT. Avastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive 6 cycles of Avastin, temozolomide, and irinotecan. Beginning a minimum of 14 days after last XRT, Avastin at 10 mg/kg with irinotecan every other week; temozolomide will be given at 200 mg/m2/day on the 1st 5 days of each 28-day cycle. The irinotecan dose will depend on whether the patient is taking enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED:125 mg/m2.)
General disorders Fatigue	8.0% 10/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Investigations Neutrophil count decreased	20.0% 25/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.
Investigations Platelet count decreased	18.4% 23/125 • 55 months Adverse events collected using Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for ClinicalTrials.gov entry.

Additional Information

Annick Desjardins, MD, FRCPC

Duke University Medical Center

Phone: 9196846173

Email: annick.desjardins@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place