Trial Outcomes & Findings for Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma (NCT NCT00501891)

Last Updated: 2013-05-27

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. \[Optional: Macdonald criteria are standard criteria in neuro-oncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of: 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).\]

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

6 months

Results posted on

2013-05-27

Participant Flow

Participant milestones

Participant milestones
Measure	Bevacizumab and Temozolomide Patients will receive up to 12 cycles of Avastin and temozolomide, and each cycle is 28 days. Avastin will be administered at 10 mg/kg every other week beginning a minimum of 7 days after a biopsy or 28 days after a craniotomy. Temozolomide will be dosed at 50 mg/m2 daily in a 28-day cycle.
Overall Study STARTED	32
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab and Temozolomide n=32 Participants Patients will receive up to 12 cycles of Avastin and temozolomide, and each cycle is 28 days. Avastin will be administered at 10 mg/kg every other week beginning a minimum of 7 days after a biopsy or 28 days after a craniotomy. Temozolomide will be dosed at 50 mg/m2 daily in a 28-day cycle.
Age Continuous	54.4 years STANDARD_DEVIATION 12.8 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Intent to treat

Outcome measures

Outcome measures
Measure	Bevacizumab and Metronomic Temozolomide n=32 Participants Patients will receive up to 12 cycles of Avastin and temozolomide, and each cycle is 28 days. Avastin will be administered at 10 mg/kg every other week beginning a minimum of 7 days after a biopsy or 28 days after a craniotomy. Temozolomide will be dosed at 50 mg/m2 daily in a 28-day cycle.
6-Month Progression-free Survival	18.8 percentage of participants Interval 7.6 to 33.7

SECONDARY outcome

Timeframe: 27 months

Population: Intent to treat

The number of participants with complete or partial response as determined by a modification of the Macdonald criteria. Complete response was defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks. Partial Response was defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks.

Outcome measures

Outcome measures
Measure	Bevacizumab and Metronomic Temozolomide n=32 Participants Patients will receive up to 12 cycles of Avastin and temozolomide, and each cycle is 28 days. Avastin will be administered at 10 mg/kg every other week beginning a minimum of 7 days after a biopsy or 28 days after a craniotomy. Temozolomide will be dosed at 50 mg/m2 daily in a 28-day cycle.
Response Rate	9 Number of participants

SECONDARY outcome

Timeframe: 27 months

Population: Intent to treat

Number of participants experiencing a Central Nervous System (CNS) hemorrhage or systemic hemorrhage

Outcome measures

Outcome measures
Measure	Bevacizumab and Metronomic Temozolomide n=32 Participants Patients will receive up to 12 cycles of Avastin and temozolomide, and each cycle is 28 days. Avastin will be administered at 10 mg/kg every other week beginning a minimum of 7 days after a biopsy or 28 days after a craniotomy. Temozolomide will be dosed at 50 mg/m2 daily in a 28-day cycle.
Incidence and Severity of CNS Hemorrhage and Systemic Hemorrhage CNS Hemorrhage	0 participants
Incidence and Severity of CNS Hemorrhage and Systemic Hemorrhage Systemic Hemorrhage	0 participants

SECONDARY outcome

Timeframe: 27 months

Population: Intent to treat

Number of participants experiencing a grade ≥4 hematologic or grade ≥3 non-hematologic toxicity

Outcome measures

Outcome measures
Measure	Bevacizumab and Metronomic Temozolomide n=32 Participants Patients will receive up to 12 cycles of Avastin and temozolomide, and each cycle is 28 days. Avastin will be administered at 10 mg/kg every other week beginning a minimum of 7 days after a biopsy or 28 days after a craniotomy. Temozolomide will be dosed at 50 mg/m2 daily in a 28-day cycle.
Incidence of Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity Grade ≥ 4 hematologic toxicities	0 participants
Incidence of Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity Grade ≥ 3 non-hematologic toxicities	14 participants

Adverse Events

Bevacizumab and Temozolomide

Serious events: 8 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bevacizumab and Temozolomide n=32 participants at risk Patients will receive up to 12 cycles of Avastin and temozolomide, and each cycle is 28 days. Avastin will be administered at 10 mg/kg every other week beginning a minimum of 7 days after a biopsy or 28 days after a craniotomy. Temozolomide will be dosed at 50 mg/m2 daily in a 28-day cycle.
Gastrointestinal disorders Colitis	3.1% 1/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Gastrointestinal disorders Diarrhea	3.1% 1/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Gastrointestinal disorders Hemorrhoids	3.1% 1/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Gastrointestinal disorders Pancreatitis	3.1% 1/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
General disorders Death NOS	9.4% 3/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Infections and infestations Lung infection	3.1% 1/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Metabolism and nutrition disorders Dehydration	3.1% 1/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Metabolism and nutrition disorders Hyperglycemia	3.1% 1/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	3.1% 1/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Nervous system disorders Cognitive disturbance	3.1% 1/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Nervous system disorders Dysphasia	3.1% 1/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Nervous system disorders Seizure	3.1% 1/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.

Other adverse events

Other adverse events
Measure	Bevacizumab and Temozolomide n=32 participants at risk Patients will receive up to 12 cycles of Avastin and temozolomide, and each cycle is 28 days. Avastin will be administered at 10 mg/kg every other week beginning a minimum of 7 days after a biopsy or 28 days after a craniotomy. Temozolomide will be dosed at 50 mg/m2 daily in a 28-day cycle.
Nervous system disorders Cognitive disturbance	6.2% 2/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Nervous system disorders Depressed level of consciousness	12.5% 4/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Nervous system disorders Dysphasia	9.4% 3/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Nervous system disorders Memory impairment	18.8% 6/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Nervous system disorders Peripheral motor neuropathy	18.8% 6/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Psychiatric disorders Confusion	9.4% 3/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Psychiatric disorders Insomnia	6.2% 2/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Reproductive system and breast disorders Sexual dysfunction, NOS	6.2% 2/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Respiratory, thoracic and mediastinal disorders Dyspnea	9.4% 3/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Skin and subcutaneous tissue disorders Rash maculo-papular	6.2% 2/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Vascular disorders Hypertension	6.2% 2/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Eye disorders Blurred vision	18.8% 6/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Gastrointestinal disorders Nausea	9.4% 3/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
General disorders Fatigue	18.8% 6/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Nervous system disorders Ataxia	15.6% 5/32 • 27 months The adverse events were gather in Common Terminology Criteria for Adverse Events (CTCAE) v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.

Additional Information

Annick Desjardins, MD

The Preston Robert Tisch Brain Tumor Center at Duke

Phone: 919-684-6173

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place