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Bevacizumab and Sorafenib in Treating Patients With Recurrent Glioblastoma Multiforme

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00621686
Recruitment Status : Completed
First Posted : February 22, 2008
Results First Posted : January 4, 2017
Last Update Posted : May 8, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Brain and Central Nervous System Tumors
Interventions Biological: bevacizumab
Drug: sorafenib tosylate
Enrollment 54
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Sorafenib + Bevacizumab/Group A Sorafenib + Bevacizumab /Group B
Hide Arm/Group Description Patients receive oral sorafenib 400 mg (200 mg twice daily) days 1-5 and 8-12 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days. Patients receive oral sorafenib 200 mg once daily on days 1-14 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days.
Period Title: Overall Study
Started 19 35
Completed 19 35
Not Completed 0 0
Arm/Group Title Sorafenib + Bevacizumab/Group A Sorafenib + Bevacizumab /Group B Total
Hide Arm/Group Description Patients receive oral sorafenib 400 mg (200 mg twice daily) days 1-5 and 8-12 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days. Patients receive oral sorafenib 200 mg once daily on days 1-14 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days. Total of all reporting groups
Overall Number of Baseline Participants 19 35 54
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 19 participants 35 participants 54 participants
54
(25 to 68)
55
(28 to 76)
55
(25 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 35 participants 54 participants
Female
7
  36.8%
12
  34.3%
19
  35.2%
Male
12
  63.2%
23
  65.7%
35
  64.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants 35 participants 54 participants
19 35 54
1.Primary Outcome
Title 6-month Progression-free Survival
Hide Description Primary Endpoint: 6-month progression free survival (PFS6): The proportion of successes will be estimated using the binomial point estimator (number of successes divided by the total number of evaluable patients) and the binomial 95% confidence interval estimated. To be classified as a success, an evaluable patient must be alive and progression-free 6 months after registration to the study. Patients who die prior to 6 months after study registration will be considered to have failed. Progression is defined as a >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions compared to pretreatment MRI and/or CT scan.
Time Frame at 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sorafenib + Bevacizumab/Group A Sorafenib + Bevacizumab /Group B
Hide Arm/Group Description:
Patients receive oral sorafenib 400 mg (200 mg twice daily) days 1-5 and 8-12 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days.
Patients receive oral sorafenib 200 mg once daily on days 1-14 and 5mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days.
Overall Number of Participants Analyzed 19 35
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.263
(0.101 to 0.514)
0.171
(0.072 to 0.343)
2.Secondary Outcome
Title Time to Progression
Hide Description Time to progression (TTP) is defined to be the length of time from study registration to a) date of disease progression as defined by section 11.0 of the protocol, or b) last follow-up. If a patient dies without documentation of disease progression, the patient will be considered to have had a tumor progression at the time of death unless there is sufficient documented evidence to conclude no progression occurred prior to death. Time to progression curves were compared via the log-rank test. Progression is defined as a >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions or unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions compared to pretreatment MRI and/or CT scan.
Time Frame Time from study registration to a) date of disease progression, or b) last follow-up; Up to 15 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sorafenib + Bevacizumab/Group A Sorafenib + Bevacizumab /Group B
Hide Arm/Group Description:
Patients receive oral sorafenib 400 mg (200 mg twice daily) days 1-5 and 8-12 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days.
Patients receive oral sorafenib 200 mg once daily on days 1-14 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days.
Overall Number of Participants Analyzed 19 35
Median (95% Confidence Interval)
Unit of Measure: months
3.61
(1.84 to 5.95)
2.66
(2.07 to 3.25)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib + Bevacizumab/Group A, Sorafenib + Bevacizumab /Group B
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.069
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Overall Survival
Hide Description Overall survival (OS) is defined as the length of time from date of registration to a) date of death due to any cause or b) last follow-up.
Time Frame Time from date of registration to a) date of death due to any cause or b) last follow-up; Up to 15 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sorafenib + Bevacizumab/Group A Sorafenib + Bevacizumab /Group B
Hide Arm/Group Description:
Patients receive oral sorafenib 400 mg (200 mg twice daily) days 1-5 and 8-12 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days.
Patients receive oral sorafenib 200 mg once daily on days 1-14 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days.
Overall Number of Participants Analyzed 19 35
Median (95% Confidence Interval)
Unit of Measure: months
5.58
(4.11 to 8.48)
5.62
(3.22 to 8.67)
Time Frame Adverse event assessments were collected ≤21 days prior to registration, prior to each new treatment cycle, at PD, withdrawal, or removal, and 28-42 days after treatment discontinuation; for up to 2 years.
Adverse Event Reporting Description This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 for adverse event monitoring and reporting. The CTCAE v3.0 can be accessed from the CTEP home page http://ctep.cancer.gov.
 
Arm/Group Title Sorafenib + Bevacizumab/Group A Sorafenib + Bevacizumab /Group B
Hide Arm/Group Description Patients receive oral sorafenib 400 mg (200 mg twice daily) days 1-5 and 8-12 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days. Patients receive oral sorafenib 200 mg once daily on days 1-14 and 5 mg/kg bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days.
All-Cause Mortality
Sorafenib + Bevacizumab/Group A Sorafenib + Bevacizumab /Group B
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Sorafenib + Bevacizumab/Group A Sorafenib + Bevacizumab /Group B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/19 (47.37%)      9/35 (25.71%)    
Blood and lymphatic system disorders     
Hemoglobin decreased  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Eye disorders     
Photophobia  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Gastrointestinal disorders     
Abdominal pain  1  0/19 (0.00%)  0 2/35 (5.71%)  2
Constipation  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Diarrhea  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Nausea  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Pancreatitis  1  1/19 (5.26%)  1 0/35 (0.00%)  0
General disorders     
Chest pain  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Disease progression  1  0/19 (0.00%)  0 2/35 (5.71%)  2
Fatigue  1  2/19 (10.53%)  3 3/35 (8.57%)  4
Fever  1  0/19 (0.00%)  0 2/35 (5.71%)  2
Infections and infestations     
Abdominal infection  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Anorectal infection  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Infection  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Pneumonia  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Injury, poisoning and procedural complications     
Wound dehiscence  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Investigations     
Alanine aminotransferase increased  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Amylase increased  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Platelet count decreased  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Weight loss  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Metabolism and nutrition disorders     
Anorexia  1  0/19 (0.00%)  0 2/35 (5.71%)  2
Blood glucose increased  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Dehydration  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Serum calcium decreased  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Serum phosphate decreased  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Muscle weakness  1  2/19 (10.53%)  3 1/35 (2.86%)  1
Pain in extremity  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Nervous system disorders     
Ataxia  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Depressed level of consciousness  1  1/19 (5.26%)  1 1/35 (2.86%)  1
Dizziness  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Headache  1  1/19 (5.26%)  1 2/35 (5.71%)  2
Mini mental status examination abnormal  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Seizure  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Speech disorder  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Psychiatric disorders     
Anxiety  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Confusion  1  0/19 (0.00%)  0 2/35 (5.71%)  2
Renal and urinary disorders     
Glomerular filtration rate decreased  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Urinary incontinence  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Dyspnea  1  1/19 (5.26%)  1 2/35 (5.71%)  2
Skin and subcutaneous tissue disorders     
Hand-and-foot syndrome  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Vascular disorders     
Hemorrhage  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Hypertension  1  0/19 (0.00%)  0 2/35 (5.71%)  2
Thrombosis  1  3/19 (15.79%)  4 0/35 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Sorafenib + Bevacizumab/Group A Sorafenib + Bevacizumab /Group B
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/19 (100.00%)      35/35 (100.00%)    
Blood and lymphatic system disorders     
Hemoglobin decreased  1  8/19 (42.11%)  25 16/35 (45.71%)  26
Cardiac disorders     
Ventricular tachycardia  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Eye disorders     
Cataract  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Optic nerve disorder  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Vision blurred  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Gastrointestinal disorders     
Abdominal pain  1  4/19 (21.05%)  6 5/35 (14.29%)  7
Diarrhea  1  9/19 (47.37%)  22 11/35 (31.43%)  24
Dry mouth  1  1/19 (5.26%)  2 1/35 (2.86%)  2
Dysphagia  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Ear, nose and throat examination abnormal  1  7/19 (36.84%)  11 8/35 (22.86%)  20
Flatulence  1  1/19 (5.26%)  1 1/35 (2.86%)  2
Mucositis oral  1  5/19 (26.32%)  6 8/35 (22.86%)  18
Nausea  1  7/19 (36.84%)  15 13/35 (37.14%)  22
Oral pain  1  1/19 (5.26%)  3 0/35 (0.00%)  0
Pancreatitis  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Vomiting  1  3/19 (15.79%)  5 5/35 (14.29%)  6
General disorders     
Disease progression  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Edema limbs  1  1/19 (5.26%)  3 1/35 (2.86%)  2
Fatigue  1  18/19 (94.74%)  118 34/35 (97.14%)  220
Fever  1  2/19 (10.53%)  2 1/35 (2.86%)  1
Pain  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Infections and infestations     
Abdominal infection  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Bronchitis  1  1/19 (5.26%)  2 0/35 (0.00%)  0
Infectious colitis  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Pharyngitis  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Pneumonia  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Sinusitis  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Skin infection  1  1/19 (5.26%)  1 1/35 (2.86%)  1
Stoma site infection  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Upper aerodigestive tract infection  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Injury, poisoning and procedural complications     
Wound dehiscence  1  0/19 (0.00%)  0 3/35 (8.57%)  6
Investigations     
Alanine aminotransferase increased  1  2/19 (10.53%)  3 2/35 (5.71%)  2
Aspartate aminotransferase increased  1  0/19 (0.00%)  0 1/35 (2.86%)  2
Bilirubin increased  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Leukocyte count decreased  1  4/19 (21.05%)  10 9/35 (25.71%)  14
Lipase increased  1  3/19 (15.79%)  3 3/35 (8.57%)  5
Lymphocyte count decreased  1  3/19 (15.79%)  6 13/35 (37.14%)  29
Neutrophil count decreased  1  2/19 (10.53%)  3 1/35 (2.86%)  3
Platelet count decreased  1  10/19 (52.63%)  52 17/35 (48.57%)  31
Weight loss  1  5/19 (26.32%)  39 10/35 (28.57%)  30
Metabolism and nutrition disorders     
Anorexia  1  8/19 (42.11%)  22 10/35 (28.57%)  26
Blood glucose increased  1  4/19 (21.05%)  4 1/35 (2.86%)  1
Dehydration  1  1/19 (5.26%)  1 1/35 (2.86%)  1
Serum albumin decreased  1  2/19 (10.53%)  2 2/35 (5.71%)  2
Serum calcium decreased  1  1/19 (5.26%)  1 2/35 (5.71%)  2
Serum phosphate decreased  1  6/19 (31.58%)  10 7/35 (20.00%)  13
Serum potassium decreased  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Serum sodium decreased  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  0/19 (0.00%)  0 2/35 (5.71%)  2
Joint pain  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Muscle weakness  1  3/19 (15.79%)  3 1/35 (2.86%)  5
Muscle weakness lower limb  1  1/19 (5.26%)  3 0/35 (0.00%)  0
Muscle weakness right-sided  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Myalgia  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Pain in extremity  1  0/19 (0.00%)  0 2/35 (5.71%)  2
Nervous system disorders     
Abducens nerve disorder  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Ataxia  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Cognitive disturbance  1  2/19 (10.53%)  3 0/35 (0.00%)  0
Depressed level of consciousness  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Encephalopathy  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Headache  1  4/19 (21.05%)  11 3/35 (8.57%)  5
Mini mental status examination abnormal  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Nystagmus  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Peripheral motor neuropathy  1  1/19 (5.26%)  1 4/35 (11.43%)  9
Peripheral sensory neuropathy  1  0/19 (0.00%)  0 3/35 (8.57%)  5
Seizure  1  0/19 (0.00%)  0 5/35 (14.29%)  5
Speech disorder  1  1/19 (5.26%)  4 0/35 (0.00%)  0
Psychiatric disorders     
Confusion  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Depression  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Insomnia  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Renal and urinary disorders     
Protein urine positive  1  0/19 (0.00%)  0 2/35 (5.71%)  3
Reproductive system and breast disorders     
Erectile dysfunction  1  1/19 (5.26%)  2 0/35 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Dyspnea  1  1/19 (5.26%)  3 2/35 (5.71%)  5
Hemorrhage nasal  1  0/19 (0.00%)  0 1/35 (2.86%)  2
Pharyngeal examination abnormal  1  2/19 (10.53%)  2 4/35 (11.43%)  9
Pharyngeal mucositis  1  2/19 (10.53%)  2 6/35 (17.14%)  11
Pharyngolaryngeal pain  1  1/19 (5.26%)  2 0/35 (0.00%)  0
Pneumonitis  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Skin and subcutaneous tissue disorders     
Alopecia  1  1/19 (5.26%)  1 0/35 (0.00%)  0
Dry skin  1  1/19 (5.26%)  5 0/35 (0.00%)  0
Hand-and-foot syndrome  1  7/19 (36.84%)  40 12/35 (34.29%)  30
Rash acneiform  1  2/19 (10.53%)  4 0/35 (0.00%)  0
Rash desquamating  1  7/19 (36.84%)  14 12/35 (34.29%)  29
Skin disorder  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Vascular disorders     
Hypertension  1  9/19 (47.37%)  22 25/35 (71.43%)  84
Hypotension  1  0/19 (0.00%)  0 1/35 (2.86%)  1
Thrombosis  1  0/19 (0.00%)  0 2/35 (5.71%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Evanthia Galanis, M.D.
Organization: Mayo Clinic
Phone: 507/284-3559
EMail: Galanis.evanthia@mayo.edu
Publications of Results:
Galanis E, Jaeckle KA, Anderson S, et al.: NCCTG phase II trial of bevacizumab in combination with sorafenib in recurrent GBM. [Abstract] J Clin Oncol 28 (Suppl 15): A-2018, 2010.
Layout table for additonal information
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00621686    
Other Study ID Numbers: NCCTG-N0776
NCI-2009-00832 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
CDR0000587614 ( Registry Identifier: PDQ (Physician Data Query) )
First Submitted: February 21, 2008
First Posted: February 22, 2008
Results First Submitted: November 7, 2016
Results First Posted: January 4, 2017
Last Update Posted: May 8, 2018