Trial Outcomes & Findings for Avastin/Radiation (XRT)/Temozolomide (Temodar) Followed by Avastin/Temodar/Topotecan for Glioblastoma (NCT NCT01004874)

Last Updated: 2022-04-13

Results Overview

Percentage of participants surviving six 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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

6 months

Results posted on

2022-04-13

Participant Flow

Participant milestones

Participant milestones
Measure	Avastin, XRT, Temodar Followed by Avastin, Temodar, Topotecan Avastin, XRT, Temodar followed by Avastin, Temodar, Topotecan : Standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation in combination with Avastin at 10 mg/kg every other week. This will be followed by Avastin at 10 mg/kg every other week, temozolomide at 150 mg/m2 daily the first 5 days in combination with topotecan at 1.5 mg/m2 (patients not taking enzyme-inducing anti-epileptic drugs) or 2.0 mg/m2 (patients taking enzyme-inducing anti-epileptic drugs) on Days 2-6 of each 28-day cycle.
Overall Study STARTED	80
Overall Study COMPLETED	80
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Avastin/Radiation (XRT)/Temozolomide (Temodar) Followed by Avastin/Temodar/Topotecan for Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Avastin, XRT, Temodar Followed by Avastin, Temodar, Topotecan n=80 Participants Avastin, XRT, Temodar followed by Avastin, Temodar, Topotecan : Standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation in combination with Avastin at 10 mg/kg every other week. This will be followed by Avastin at 10 mg/kg every other week, temozolomide at 150 mg/m2 daily the first 5 days in combination with topotecan at 1.5 mg/m2 (patients not taking enzyme-inducing anti-epileptic drugs) or 2.0 mg/m2 (patients taking enzyme-inducing anti-epileptic drugs) on Days 2-6 of each 28-day cycle.
Age, Continuous	53.7 years STANDARD_DEVIATION 9.6 • n=39 Participants
Sex: Female, Male Female	29 Participants n=39 Participants
Sex: Female, Male Male	51 Participants n=39 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Intent to treat

Outcome measures

Outcome measures
Measure	Bevacizumab, XRT, Temozolomide, Topotecan n=80 Participants Bevacizumab, XRT, Temozolomide followed by Bevacizumab, Temozolomide, Topotecan : Standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation in combination with Bevacizumab at 10 mg/kg every other week. This will be followed by Bevacizumab at 10 mg/kg every other week, temozolomide at 150 mg/m2 daily the first 5 days in combination with topotecan at 1.5 mg/m2 (patients not taking enzyme-inducing anti-epileptic drugs) or 2.0 mg/m2 (patients taking enzyme-inducing anti-epileptic drugs) on Days 2-6 of each 28-day cycle.
6-month Progression-free Survival	88.8 percentage of participants Interval 79.5 to 94.0

SECONDARY outcome

Timeframe: One year and two years

Population: Intent to treat

Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date.

Outcome measures

Outcome measures
Measure	Bevacizumab, XRT, Temozolomide, Topotecan n=80 Participants Bevacizumab, XRT, Temozolomide followed by Bevacizumab, Temozolomide, Topotecan : Standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation in combination with Bevacizumab at 10 mg/kg every other week. This will be followed by Bevacizumab at 10 mg/kg every other week, temozolomide at 150 mg/m2 daily the first 5 days in combination with topotecan at 1.5 mg/m2 (patients not taking enzyme-inducing anti-epileptic drugs) or 2.0 mg/m2 (patients taking enzyme-inducing anti-epileptic drugs) on Days 2-6 of each 28-day cycle.
One and Two Year Overall Survival One year Overall Survival	73.8 percentage of participants Interval 62.6 to 82.0
One and Two Year Overall Survival Two year Overall Survival	35.6 percentage of participants Interval 23.9 to 47.6

SECONDARY outcome

Timeframe: 27 months

Population: Intent to treat

OS was defined as time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.

Outcome measures

Outcome measures
Measure	Bevacizumab, XRT, Temozolomide, Topotecan n=80 Participants Bevacizumab, XRT, Temozolomide followed by Bevacizumab, Temozolomide, Topotecan : Standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation in combination with Bevacizumab at 10 mg/kg every other week. This will be followed by Bevacizumab at 10 mg/kg every other week, temozolomide at 150 mg/m2 daily the first 5 days in combination with topotecan at 1.5 mg/m2 (patients not taking enzyme-inducing anti-epileptic drugs) or 2.0 mg/m2 (patients taking enzyme-inducing anti-epileptic drugs) on Days 2-6 of each 28-day cycle.
Median Overall Survival	17.2 months Interval 15.5 to 21.5

SECONDARY outcome

Timeframe: 27 months

Population: Intent to treat

Number of times a CNS hemorrhage or systemic hemorrhage was experienced

Outcome measures

Outcome measures
Measure	Bevacizumab, XRT, Temozolomide, Topotecan n=80 Participants Bevacizumab, XRT, Temozolomide followed by Bevacizumab, Temozolomide, Topotecan : Standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation in combination with Bevacizumab at 10 mg/kg every other week. This will be followed by Bevacizumab at 10 mg/kg every other week, temozolomide at 150 mg/m2 daily the first 5 days in combination with topotecan at 1.5 mg/m2 (patients not taking enzyme-inducing anti-epileptic drugs) or 2.0 mg/m2 (patients taking enzyme-inducing anti-epileptic drugs) on Days 2-6 of each 28-day cycle.
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage Grade 2 central nervous system (CNS) hemorrhage	1 participants
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage Grade 3 CNS hemorrhage	0 participants
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage Grade 4 CNS hemorrhage	2 participants

SECONDARY outcome

Timeframe: 27 months

Population: Intent to treat

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

Outcome measures

Outcome measures
Measure	Bevacizumab, XRT, Temozolomide, Topotecan n=80 Participants Bevacizumab, XRT, Temozolomide followed by Bevacizumab, Temozolomide, Topotecan : Standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation in combination with Bevacizumab at 10 mg/kg every other week. This will be followed by Bevacizumab at 10 mg/kg every other week, temozolomide at 150 mg/m2 daily the first 5 days in combination with topotecan at 1.5 mg/m2 (patients not taking enzyme-inducing anti-epileptic drugs) or 2.0 mg/m2 (patients taking enzyme-inducing anti-epileptic drugs) on Days 2-6 of each 28-day cycle.
Number of Patients Experiencing a Greater Than or Equal to Grade 4 Hematologic or a Greater Than or Equal to Grade 3 Non-hematologic Toxicity Greater than equal Gr.4 hematologic toxicites	23 participants
Number of Patients Experiencing a Greater Than or Equal to Grade 4 Hematologic or a Greater Than or Equal to Grade 3 Non-hematologic Toxicity Greater than equal Gr.3 non-hematologic toxicites	17 participants

SECONDARY outcome

Timeframe: 27 months

Population: Intent to treat

PFS was defined as time in months from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.

Outcome measures

Outcome measures
Measure	Bevacizumab, XRT, Temozolomide, Topotecan n=80 Participants Bevacizumab, XRT, Temozolomide followed by Bevacizumab, Temozolomide, Topotecan : Standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation in combination with Bevacizumab at 10 mg/kg every other week. This will be followed by Bevacizumab at 10 mg/kg every other week, temozolomide at 150 mg/m2 daily the first 5 days in combination with topotecan at 1.5 mg/m2 (patients not taking enzyme-inducing anti-epileptic drugs) or 2.0 mg/m2 (patients taking enzyme-inducing anti-epileptic drugs) on Days 2-6 of each 28-day cycle.
Median Progression-free Survival	11.1 months Interval 9.4 to 13.6

Adverse Events

Avastin, XRT, Temodar Followed by Avastin, Temodar, Topotecan

Serious events: 17 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Avastin, XRT, Temodar Followed by Avastin, Temodar, Topotecan n=80 participants at risk Avastin, XRT, Temodar followed by Avastin, Temodar, Topotecan : Standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation in combination with Avastin at 10 mg/kg every other week. This will be followed by Avastin at 10 mg/kg every other week, temozolomide at 150 mg/m2 daily the first 5 days in combination with topotecan at 1.5 mg/m2 (patients not taking enzyme-inducing anti-epileptic drugs) or 2.0 mg/m2 (patients taking enzyme-inducing anti-epileptic drugs) on Days 2-6 of each 28-day cycle.
General disorders Death NOS	2.5% 2/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
General disorders Fever	2.5% 2/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Infections and infestations Abdominal infection	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Infections and infestations Infections and infestations - Other, specify: Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Infections and infestations Infections and infestations - Other, specify: Septic Shock	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Infections and infestations Urinary tract infection	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Infections and infestations Wound infection	2.5% 2/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Investigations Neutrophil count decreased	6.2% 5/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Investigations Platelet count decreased	8.8% 7/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Investigations White blood cell decreased	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Metabolism and nutrition disorders Hyperglycemia	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Metabolism and nutrition disorders Hypokalemia	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Metabolism and nutrition disorders Hyponatremia	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Nervous system disorders Cognitive disturbance	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Nervous system disorders Intracranial hemorrhage	3.8% 3/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Nervous system disorders Ischemia cerebrovascular	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Nervous system disorders Seizure	5.0% 4/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Psychiatric disorders Confusion	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Vascular disorders Hypertension	1.2% 1/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Vascular disorders Thromboembolic event	3.8% 3/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.

Other adverse events

Other adverse events
Measure	Avastin, XRT, Temodar Followed by Avastin, Temodar, Topotecan n=80 participants at risk Avastin, XRT, Temodar followed by Avastin, Temodar, Topotecan : Standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation in combination with Avastin at 10 mg/kg every other week. This will be followed by Avastin at 10 mg/kg every other week, temozolomide at 150 mg/m2 daily the first 5 days in combination with topotecan at 1.5 mg/m2 (patients not taking enzyme-inducing anti-epileptic drugs) or 2.0 mg/m2 (patients taking enzyme-inducing anti-epileptic drugs) on Days 2-6 of each 28-day cycle.
Investigations Neutrophil count decreased	21.2% 17/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.
Investigations Platelet count decreased	32.5% 26/80 • 27 months Adverse events gathered in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0 and converted to v.4.0 for entry into ClinicalTrials.gov.

Additional Information

Dr. Annick Desjardins, MD, FRCPC

Duke University Medical Center

Phone: 9196846173

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place