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Bevacizumab With or Without Trebananib in Treating Patients With Recurrent Brain Tumors

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: NCT01609790
Recruitment Status : Active, not recruiting
First Posted : June 1, 2012
Results First Posted : February 27, 2017
Last Update Posted : June 13, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Giant Cell Glioblastoma
Glioblastoma
Gliosarcoma
Oligodendroglioma
Recurrent Brain Neoplasm
Recurrent Glioblastoma
Interventions Biological: Bevacizumab
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Other: Placebo
Biological: Trebananib
Enrollment 137
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort 1: Safety Run-In Cohort 2: Bevacizumab+Placebo Cohort 2: Bevacizumab+AMG 386
Hide Arm/Group Description Bevacizumab every 2 weeks + AMG 386 weekly until disease progression. Bevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386 Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
Period Title: Overall Study
Started 7 65 65
Completed 6 [1] 58 [1] 57 [1]
Not Completed 1 7 8
Reason Not Completed
Protocol Violation             1             7             8
[1]
Subjects with data available for analysis are considered to have completed the study.
Arm/Group Title Cohort 1: Safety Run-In Cohort 2: Bevacizumab+Placebo Cohort 2: Bevacizumab+AMG 386 Total
Hide Arm/Group Description Bevacizumab every 2 weeks + AMG 386 weekly until disease progression. Bevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386 Bevacizumab every 2 weeks + AMG 386 weekly until disease progression. Total of all reporting groups
Overall Number of Baseline Participants 6 58 57 121
Hide Baseline Analysis Population Description
All eligible patients.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 6 participants 58 participants 57 participants 121 participants
56
(28 to 75)
58
(22 to 79)
57
(30 to 80)
58
(22 to 80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 58 participants 57 participants 121 participants
Female
1
  16.7%
22
  37.9%
25
  43.9%
48
  39.7%
Male
5
  83.3%
36
  62.1%
32
  56.1%
73
  60.3%
1.Primary Outcome
Title Number of Patients Experiencing of Dose-limiting Toxicity (Cohort 1)
Hide Description Dose-limiting toxicity (DLT), defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and meets any of the criteria below. Any DLT must be a toxicity possibly related to protocol treatment during first 4 weeks: grade 4 hematologic toxicity, grade 3/4 thrombocytopenia, or grade 3/4 non-hematologic toxicity; Gastrointestinal fistula, bowel perforation, intracranial hemorrhage, wound dehiscence, or reversible posterior leukoencephalopathy of any grade; Delay of treatment > 28 days. If 2+ of patients experience a DLT among 6 eligible patients, this drug combination will be considered unsafe and a lower dose of AMG will be explored; otherwise conclude that this drug combination is safe. The probability of claiming safe dose is no more than 16% when the true DLT rate is >45%, and the probability of claiming safe dose is at least 78% when the true DLT rate is <= 15%.
Time Frame From start of treatment to 4 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients who started study treatment
Arm/Group Title Safety Run-In
Hide Arm/Group Description:
Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: participants
0
2.Primary Outcome
Title Six-month Progression-free Survival (Cohort 2)
Hide Description As determined by central review of MRI exams, assessed using RANO criteria for progression that is defined by any of the following: > 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared to the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids; Significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation of therapy, not due to co-morbid events; Any new lesion; Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose; Failure to return for evaluation due to death or deteriorating condition; Clear progression of non-measurable disease.
Time Frame From randomization to six months.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized patients evaluable for 6 months progression-free survival (PFS).
Arm/Group Title Cohort 2: Bevacizumab+Placebo Cohort 2: Bevacizumab+AMG 386
Hide Arm/Group Description:
Bevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386
Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
Overall Number of Participants Analyzed 56 53
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
41.1
(28.2 to 54.0)
22.6
(11.4 to 33.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Bevacizumab+Placebo, Cohort 2: Bevacizumab+AMG 386
Comments Assuming a 36% 6-month (6m) rate in the placebo arm [from the March 2009 Food and Drug Administration (FDA) briefing], a 55% rate in the AMG 386 arm, and an exponential distribution corresponds to median PFS of 4.1 and 7 months, respectively, with a hazard ratio of 0.59 (AMG 386 arm vs. placebo arm). A total of 114 patients (57 per arm) will yield 85% power to detect an absolute 19% difference of 6m PFS rate at a 1-sided alpha level of 0.15 based on a 2-sample proportion test.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.98
Comments [Not Specified]
Method Z-test
Comments One-sided test, significance level 0.15
3.Secondary Outcome
Title Incidence of Grade 3+ Treatment-related Toxicity, Measured by CTCAE v. 4 (Cohort 2)
Hide Description Adverse events (AEs) are graded by using CTCAE 4.0. Possibly/probably/definitely related to protocol treatment AEs are considered.
Time Frame From start of treatment up to 3 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized and eligible patients who started protocol treatment.
Arm/Group Title Cohort 2: Bevacizumab+Placebo Cohort 2: Bevacizumab+AMG 386
Hide Arm/Group Description:
Bevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386
Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
Overall Number of Participants Analyzed 57 57
Measure Type: Number
Unit of Measure: participants
21 20
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Bevacizumab+Placebo, Cohort 2: Bevacizumab+AMG 386
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.85
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
4.Secondary Outcome
Title Overall Survival (Cohort 2)
Hide Description Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur when all patients had been potentially followed for at least 6 months.
Time Frame From randomization up to 3 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and eligible patients.
Arm/Group Title Cohort 2: Bevacizumab+Placebo Cohort 2: Bevacizumab+AMG 386
Hide Arm/Group Description:
Bevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386
Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
Overall Number of Participants Analyzed 58 57
Median (95% Confidence Interval)
Unit of Measure: Months
11.5
(8.4 to 14.2)
7.5
(6.8 to 10.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Bevacizumab+Placebo, Cohort 2: Bevacizumab+AMG 386
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.09
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
0.95 to 2.27
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Progression-free Survival (Cohort 2)
Hide Description Progression-free survival time is measured from randomization to the date of first progression or death or, otherwise, the last follow-up date on which the patient was reported alive. This analysis was planned to occur when all patients had been potentially followed for at least 6 months.
Time Frame From randomization up to 3 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and eligible patients.
Arm/Group Title Cohort 2: Bevacizumab+Placebo Cohort 2: Bevacizumab+AMG 386
Hide Arm/Group Description:
Bevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386
Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
Overall Number of Participants Analyzed 58 57
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.8
(3.8 to 7.1)
4.2
(3.7 to 5.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Bevacizumab+Placebo, Cohort 2: Bevacizumab+AMG 386
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.51
Confidence Interval (2-Sided) 95%
1.02 to 2.24
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Radiographic Response Rate (Cohort 2)
Hide Description Proportion of patients with best overall response of complete response (CR) or partial response (PR) recorded from the start of the treatment until disease progression/recurrence. Response determined by site-reported radiology review of MRI exams using Response Assessment in Neuro-Oncology Criteria (RANO) criteria. CR: Complete disappearance of all enhancing measurable disease (MD) + non-measurable disease (NMD) sustained >= 4 wks; No new lesions; Stable or improved non-enhancing (T2/FLAIR) lesions; Off corticosteroids (or on physiologic replacement doses only); Stable/improved clinically. PR: >= 50% decrease vs. baseline of sum of products of perpendicular diameters of all measurable enhancing lesions sustained >= 4 wks; No progression of NMD; No new lesions; Stable/improved non-enhancing (T2/FLAIR) lesions on <= dose of corticosteroids vs. baseline scan; Corticosteroid dose at evaluation scan <= baseline scan dose; Stable or improved clinically. NMD only cannot be a CR or PR.
Time Frame From randomization up to 3 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized and eligible patients.
Arm/Group Title Cohort 2: Bevacizumab+Placebo Cohort 2: Bevacizumab+AMG 386
Hide Arm/Group Description:
Bevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386
Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
Overall Number of Participants Analyzed 58 57
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
5.9
(0 to 12.3)
4.2
(0 to 9.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Bevacizumab+Placebo, Cohort 2: Bevacizumab+AMG 386
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Patients Requiring Dose Reduction/Interruption or Discontinuation in the First 2 and Subsequent Courses (Cohort 1)
Hide Description Feasibility of trebananib weekly in combination with bevacizumab every 2 weeks, measured by the percentage of patients requiring dose reduction/interruption or discontinuation in the first 2 and subsequent courses (Cohort 1)
Time Frame From randomization up to 3 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Eligible patients
Arm/Group Title Safety Run-In
Hide Arm/Group Description:
Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
In first 2 cycles
6
 100.0%
In first 6 cycles
3
  50.0%
In first 12 cycles
5
  83.3%
8.Other Pre-specified Outcome
Title Tumor Genotype, Expression Profile, and Circulating Angiogenesis Biomarkers (Cohort 2)
Hide Description Biomarker data has not yet been obtained and therefore this outcome measure cannot yet be reported.
Time Frame From randomization to date of death or last followup. Statistical analysis occurs when tumor genotype, expression profile and circulating angiogenesis biomarkers have been determined from the tissue specimens.
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description Randomized and eligible patients who started protocol treatment are included in the adverse event tables. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
 
Arm/Group Title Cohort 1: Safety Run-In Cohort 2: Bevacizumab+Placebo Cohort 2: Bevacizumab+AMG 386
Hide Arm/Group Description Bevacizumab every 2 weeks + AMG 386 weekly until disease progression. Bevacizumab every 2 weeks + placebo weekly until disease progression. Patients who progress will be allowed to cross over and receive treatment with bevacizumab + AMG 386 Bevacizumab every 2 weeks + AMG 386 weekly until disease progression.
All-Cause Mortality
Cohort 1: Safety Run-In Cohort 2: Bevacizumab+Placebo Cohort 2: Bevacizumab+AMG 386
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cohort 1: Safety Run-In Cohort 2: Bevacizumab+Placebo Cohort 2: Bevacizumab+AMG 386
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/6 (83.33%)   22/57 (38.60%)   20/57 (35.09%) 
Cardiac disorders       
Ventricular fibrillation * 1  0/6 (0.00%)  0/57 (0.00%)  1/57 (1.75%) 
Endocrine disorders       
Hyperthyroidism * 1  0/6 (0.00%)  0/57 (0.00%)  1/57 (1.75%) 
Gastrointestinal disorders       
Retroperitoneal hemorrhage * 1  0/6 (0.00%)  0/57 (0.00%)  1/57 (1.75%) 
General disorders       
Edema limbs * 1  0/6 (0.00%)  1/57 (1.75%)  1/57 (1.75%) 
Flu like symptoms * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Gait disturbance * 1  0/6 (0.00%)  3/57 (5.26%)  0/57 (0.00%) 
Non-cardiac chest pain * 1  0/6 (0.00%)  0/57 (0.00%)  1/57 (1.75%) 
Infections and infestations       
Infections and infestations - Other * 1  0/6 (0.00%)  0/57 (0.00%)  1/57 (1.75%) 
Lung infection * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Meningitis * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Sepsis * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Skin infection * 1  1/6 (16.67%)  1/57 (1.75%)  1/57 (1.75%) 
Urinary tract infection * 1  2/6 (33.33%)  1/57 (1.75%)  1/57 (1.75%) 
Wound infection * 1  0/6 (0.00%)  0/57 (0.00%)  1/57 (1.75%) 
Injury, poisoning and procedural complications       
Fall * 1  0/6 (0.00%)  1/57 (1.75%)  1/57 (1.75%) 
Hip fracture * 1  1/6 (16.67%)  0/57 (0.00%)  0/57 (0.00%) 
Spinal fracture * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Wound dehiscence * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Investigations       
Aspartate aminotransferase increased * 1  1/6 (16.67%)  0/57 (0.00%)  0/57 (0.00%) 
Lymphocyte count decreased * 1  0/6 (0.00%)  0/57 (0.00%)  1/57 (1.75%) 
Platelet count decreased * 1  0/6 (0.00%)  0/57 (0.00%)  1/57 (1.75%) 
Metabolism and nutrition disorders       
Hyperglycemia * 1  1/6 (16.67%)  1/57 (1.75%)  1/57 (1.75%) 
Hyponatremia * 1  0/6 (0.00%)  3/57 (5.26%)  0/57 (0.00%) 
Metabolism and nutrition disorders - Other * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthritis * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Generalized muscle weakness * 1  0/6 (0.00%)  2/57 (3.51%)  1/57 (1.75%) 
Muscle weakness lower limb * 1  0/6 (0.00%)  1/57 (1.75%)  2/57 (3.51%) 
Muscle weakness upper limb * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other * 1  1/6 (16.67%)  2/57 (3.51%)  3/57 (5.26%) 
Nervous system disorders       
Aphonia * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Ataxia * 1  0/6 (0.00%)  0/57 (0.00%)  1/57 (1.75%) 
Cerebrospinal fluid leakage * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Cognitive disturbance * 1  0/6 (0.00%)  2/57 (3.51%)  1/57 (1.75%) 
Depressed level of consciousness * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Dizziness * 1  0/6 (0.00%)  0/57 (0.00%)  1/57 (1.75%) 
Dysphasia * 1  0/6 (0.00%)  2/57 (3.51%)  0/57 (0.00%) 
Encephalopathy * 1  0/6 (0.00%)  2/57 (3.51%)  0/57 (0.00%) 
Headache * 1  0/6 (0.00%)  1/57 (1.75%)  1/57 (1.75%) 
Intracranial hemorrhage * 1  0/6 (0.00%)  1/57 (1.75%)  1/57 (1.75%) 
Memory impairment * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Nervous system disorders - Other * 1  0/6 (0.00%)  0/57 (0.00%)  2/57 (3.51%) 
Seizure * 1  2/6 (33.33%)  4/57 (7.02%)  4/57 (7.02%) 
Stroke * 1  0/6 (0.00%)  2/57 (3.51%)  1/57 (1.75%) 
Transient ischemic attacks * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Psychiatric disorders       
Confusion * 1  0/6 (0.00%)  2/57 (3.51%)  3/57 (5.26%) 
Delirium * 1  0/6 (0.00%)  1/57 (1.75%)  1/57 (1.75%) 
Renal and urinary disorders       
Acute kidney injury * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Adult respiratory distress syndrome * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Pleural effusion * 1  0/6 (0.00%)  1/57 (1.75%)  0/57 (0.00%) 
Respiratory failure  1  0/6 (0.00%)  0/57 (0.00%)  1/57 (1.75%) 
Vascular disorders       
Hypertension * 1  0/6 (0.00%)  1/57 (1.75%)  3/57 (5.26%) 
Thromboembolic event * 1  0/6 (0.00%)  1/57 (1.75%)  2/57 (3.51%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1: Safety Run-In Cohort 2: Bevacizumab+Placebo Cohort 2: Bevacizumab+AMG 386
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   57/57 (100.00%)   54/57 (94.74%) 
Blood and lymphatic system disorders       
Anemia * 1  3/6 (50.00%)  14/57 (24.56%)  9/57 (15.79%) 
Cardiac disorders       
Sinus tachycardia * 1  1/6 (16.67%)  1/57 (1.75%)  0/57 (0.00%) 
Ear and labyrinth disorders       
Hearing impaired * 1  1/6 (16.67%)  0/57 (0.00%)  2/57 (3.51%) 
Endocrine disorders       
Cushingoid * 1  1/6 (16.67%)  0/57 (0.00%)  2/57 (3.51%) 
Eye disorders       
Blurred vision * 1  0/6 (0.00%)  4/57 (7.02%)  7/57 (12.28%) 
Dry eye * 1  1/6 (16.67%)  1/57 (1.75%)  1/57 (1.75%) 
Eye disorders - Other * 1  0/6 (0.00%)  5/57 (8.77%)  9/57 (15.79%) 
Gastrointestinal disorders       
Abdominal pain * 1  0/6 (0.00%)  4/57 (7.02%)  5/57 (8.77%) 
Constipation * 1  3/6 (50.00%)  15/57 (26.32%)  6/57 (10.53%) 
Diarrhea * 1  2/6 (33.33%)  13/57 (22.81%)  8/57 (14.04%) 
Dry mouth * 1  0/6 (0.00%)  3/57 (5.26%)  1/57 (1.75%) 
Dyspepsia * 1  0/6 (0.00%)  6/57 (10.53%)  3/57 (5.26%) 
Dysphagia * 1  1/6 (16.67%)  1/57 (1.75%)  3/57 (5.26%) 
Fecal incontinence * 1  1/6 (16.67%)  2/57 (3.51%)  0/57 (0.00%) 
Gastrointestinal disorders - Other * 1  1/6 (16.67%)  3/57 (5.26%)  1/57 (1.75%) 
Mucositis oral * 1  1/6 (16.67%)  4/57 (7.02%)  4/57 (7.02%) 
Nausea * 1  2/6 (33.33%)  14/57 (24.56%)  8/57 (14.04%) 
Vomiting * 1  2/6 (33.33%)  11/57 (19.30%)  2/57 (3.51%) 
General disorders       
Chills * 1  0/6 (0.00%)  3/57 (5.26%)  0/57 (0.00%) 
Edema face * 1  0/6 (0.00%)  1/57 (1.75%)  4/57 (7.02%) 
Edema limbs * 1  2/6 (33.33%)  12/57 (21.05%)  12/57 (21.05%) 
Fatigue * 1  4/6 (66.67%)  38/57 (66.67%)  37/57 (64.91%) 
Fever * 1  1/6 (16.67%)  6/57 (10.53%)  0/57 (0.00%) 
Gait disturbance * 1  1/6 (16.67%)  13/57 (22.81%)  7/57 (12.28%) 
General disorders and administration site conditions - Other * 1  0/6 (0.00%)  4/57 (7.02%)  2/57 (3.51%) 
Injection site reaction * 1  1/6 (16.67%)  1/57 (1.75%)  1/57 (1.75%) 
Localized edema * 1  0/6 (0.00%)  4/57 (7.02%)  1/57 (1.75%) 
Malaise * 1  1/6 (16.67%)  1/57 (1.75%)  0/57 (0.00%) 
Non-cardiac chest pain * 1  1/6 (16.67%)  2/57 (3.51%)  2/57 (3.51%) 
Pain * 1  2/6 (33.33%)  8/57 (14.04%)  8/57 (14.04%) 
Infections and infestations       
Esophageal infection * 1  1/6 (16.67%)  0/57 (0.00%)  0/57 (0.00%) 
Soft tissue infection * 1  1/6 (16.67%)  0/57 (0.00%)  0/57 (0.00%) 
Upper respiratory infection * 1  0/6 (0.00%)  3/57 (5.26%)  3/57 (5.26%) 
Urinary tract infection * 1  1/6 (16.67%)  1/57 (1.75%)  4/57 (7.02%) 
Vaginal infection * 1  1/6 (16.67%)  0/57 (0.00%)  0/57 (0.00%) 
Injury, poisoning and procedural complications       
Bruising * 1  0/6 (0.00%)  4/57 (7.02%)  4/57 (7.02%) 
Fall * 1  2/6 (33.33%)  5/57 (8.77%)  9/57 (15.79%) 
Fracture * 1  1/6 (16.67%)  1/57 (1.75%)  1/57 (1.75%) 
Investigations       
Activated partial thromboplastin time prolonged * 1  0/6 (0.00%)  2/57 (3.51%)  3/57 (5.26%) 
Alanine aminotransferase increased * 1  3/6 (50.00%)  15/57 (26.32%)  9/57 (15.79%) 
Alkaline phosphatase increased * 1  2/6 (33.33%)  5/57 (8.77%)  4/57 (7.02%) 
Aspartate aminotransferase increased * 1  0/6 (0.00%)  9/57 (15.79%)  6/57 (10.53%) 
Blood bilirubin increased * 1  0/6 (0.00%)  3/57 (5.26%)  3/57 (5.26%) 
CPK increased * 1  1/6 (16.67%)  0/57 (0.00%)  0/57 (0.00%) 
Creatinine increased * 1  1/6 (16.67%)  1/57 (1.75%)  2/57 (3.51%) 
Investigations - Other * 1  1/6 (16.67%)  3/57 (5.26%)  3/57 (5.26%) 
Lymphocyte count decreased * 1  2/6 (33.33%)  17/57 (29.82%)  15/57 (26.32%) 
Neutrophil count decreased * 1  0/6 (0.00%)  6/57 (10.53%)  4/57 (7.02%) 
Platelet count decreased * 1  1/6 (16.67%)  10/57 (17.54%)  10/57 (17.54%) 
Weight gain * 1  1/6 (16.67%)  0/57 (0.00%)  3/57 (5.26%) 
Weight loss * 1  2/6 (33.33%)  6/57 (10.53%)  2/57 (3.51%) 
White blood cell decreased * 1  1/6 (16.67%)  11/57 (19.30%)  10/57 (17.54%) 
Metabolism and nutrition disorders       
Anorexia * 1  2/6 (33.33%)  10/57 (17.54%)  5/57 (8.77%) 
Dehydration * 1  1/6 (16.67%)  2/57 (3.51%)  3/57 (5.26%) 
Hyperglycemia * 1  2/6 (33.33%)  22/57 (38.60%)  16/57 (28.07%) 
Hyperkalemia * 1  0/6 (0.00%)  4/57 (7.02%)  2/57 (3.51%) 
Hypermagnesemia * 1  0/6 (0.00%)  3/57 (5.26%)  5/57 (8.77%) 
Hypernatremia * 1  1/6 (16.67%)  1/57 (1.75%)  2/57 (3.51%) 
Hypoalbuminemia * 1  2/6 (33.33%)  5/57 (8.77%)  5/57 (8.77%) 
Hypocalcemia * 1  2/6 (33.33%)  3/57 (5.26%)  5/57 (8.77%) 
Hypoglycemia * 1  1/6 (16.67%)  2/57 (3.51%)  2/57 (3.51%) 
Hypokalemia * 1  1/6 (16.67%)  8/57 (14.04%)  5/57 (8.77%) 
Hypomagnesemia * 1  1/6 (16.67%)  6/57 (10.53%)  4/57 (7.02%) 
Hyponatremia * 1  2/6 (33.33%)  9/57 (15.79%)  7/57 (12.28%) 
Hypophosphatemia * 1  1/6 (16.67%)  8/57 (14.04%)  5/57 (8.77%) 
Metabolism and nutrition disorders - Other * 1  0/6 (0.00%)  5/57 (8.77%)  1/57 (1.75%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  2/6 (33.33%)  11/57 (19.30%)  5/57 (8.77%) 
Arthritis * 1  1/6 (16.67%)  0/57 (0.00%)  2/57 (3.51%) 
Back pain * 1  2/6 (33.33%)  7/57 (12.28%)  2/57 (3.51%) 
Bone pain * 1  1/6 (16.67%)  2/57 (3.51%)  0/57 (0.00%) 
Flank pain * 1  1/6 (16.67%)  0/57 (0.00%)  0/57 (0.00%) 
Generalized muscle weakness * 1  3/6 (50.00%)  9/57 (15.79%)  10/57 (17.54%) 
Muscle weakness left-sided * 1  1/6 (16.67%)  12/57 (21.05%)  6/57 (10.53%) 
Muscle weakness lower limb * 1  1/6 (16.67%)  5/57 (8.77%)  8/57 (14.04%) 
Muscle weakness right-sided * 1  0/6 (0.00%)  3/57 (5.26%)  4/57 (7.02%) 
Muscle weakness upper limb * 1  1/6 (16.67%)  2/57 (3.51%)  1/57 (1.75%) 
Musculoskeletal and connective tissue disorder - Other * 1  0/6 (0.00%)  2/57 (3.51%)  3/57 (5.26%) 
Myalgia * 1  1/6 (16.67%)  3/57 (5.26%)  3/57 (5.26%) 
Neck pain * 1  1/6 (16.67%)  2/57 (3.51%)  1/57 (1.75%) 
Pain in extremity * 1  2/6 (33.33%)  9/57 (15.79%)  9/57 (15.79%) 
Nervous system disorders       
Amnesia * 1  1/6 (16.67%)  1/57 (1.75%)  2/57 (3.51%) 
Ataxia * 1  2/6 (33.33%)  5/57 (8.77%)  4/57 (7.02%) 
Cognitive disturbance * 1  0/6 (0.00%)  8/57 (14.04%)  2/57 (3.51%) 
Concentration impairment * 1  1/6 (16.67%)  0/57 (0.00%)  2/57 (3.51%) 
Depressed level of consciousness * 1  1/6 (16.67%)  2/57 (3.51%)  0/57 (0.00%) 
Dizziness * 1  2/6 (33.33%)  11/57 (19.30%)  11/57 (19.30%) 
Dysarthria * 1  0/6 (0.00%)  6/57 (10.53%)  6/57 (10.53%) 
Dysgeusia * 1  1/6 (16.67%)  0/57 (0.00%)  1/57 (1.75%) 
Dysphasia * 1  1/6 (16.67%)  10/57 (17.54%)  7/57 (12.28%) 
Facial muscle weakness * 1  2/6 (33.33%)  0/57 (0.00%)  0/57 (0.00%) 
Facial nerve disorder * 1  1/6 (16.67%)  0/57 (0.00%)  0/57 (0.00%) 
Headache * 1  2/6 (33.33%)  32/57 (56.14%)  19/57 (33.33%) 
Lethargy * 1  1/6 (16.67%)  1/57 (1.75%)  1/57 (1.75%) 
Memory impairment * 1  1/6 (16.67%)  11/57 (19.30%)  10/57 (17.54%) 
Nervous system disorders - Other * 1  1/6 (16.67%)  9/57 (15.79%)  7/57 (12.28%) 
Paresthesia * 1  1/6 (16.67%)  7/57 (12.28%)  8/57 (14.04%) 
Peripheral sensory neuropathy * 1  2/6 (33.33%)  5/57 (8.77%)  5/57 (8.77%) 
Seizure * 1  1/6 (16.67%)  11/57 (19.30%)  5/57 (8.77%) 
Somnolence * 1  1/6 (16.67%)  0/57 (0.00%)  1/57 (1.75%) 
Tremor * 1  0/6 (0.00%)  5/57 (8.77%)  3/57 (5.26%) 
Psychiatric disorders       
Agitation * 1  1/6 (16.67%)  1/57 (1.75%)  2/57 (3.51%) 
Anxiety * 1  0/6 (0.00%)  9/57 (15.79%)  4/57 (7.02%) 
Confusion * 1  3/6 (50.00%)  7/57 (12.28%)  6/57 (10.53%) 
Depression * 1  1/6 (16.67%)  9/57 (15.79%)  9/57 (15.79%) 
Insomnia * 1  3/6 (50.00%)  9/57 (15.79%)  11/57 (19.30%) 
Renal and urinary disorders       
Hematuria * 1  2/6 (33.33%)  5/57 (8.77%)  5/57 (8.77%) 
Proteinuria * 1  1/6 (16.67%)  9/57 (15.79%)  7/57 (12.28%) 
Urinary frequency * 1  2/6 (33.33%)  3/57 (5.26%)  4/57 (7.02%) 
Urinary incontinence * 1  3/6 (50.00%)  5/57 (8.77%)  4/57 (7.02%) 
Urinary retention * 1  1/6 (16.67%)  0/57 (0.00%)  0/57 (0.00%) 
Urinary urgency * 1  1/6 (16.67%)  1/57 (1.75%)  0/57 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Allergic rhinitis * 1  1/6 (16.67%)  2/57 (3.51%)  1/57 (1.75%) 
Cough * 1  2/6 (33.33%)  12/57 (21.05%)  8/57 (14.04%) 
Dyspnea * 1  1/6 (16.67%)  7/57 (12.28%)  3/57 (5.26%) 
Epistaxis * 1  0/6 (0.00%)  7/57 (12.28%)  3/57 (5.26%) 
Hoarseness * 1  0/6 (0.00%)  6/57 (10.53%)  4/57 (7.02%) 
Laryngeal inflammation * 1  1/6 (16.67%)  1/57 (1.75%)  0/57 (0.00%) 
Nasal congestion * 1  0/6 (0.00%)  4/57 (7.02%)  0/57 (0.00%) 
Postnasal drip * 1  2/6 (33.33%)  1/57 (1.75%)  1/57 (1.75%) 
Productive cough * 1  2/6 (33.33%)  2/57 (3.51%)  1/57 (1.75%) 
Sore throat * 1  1/6 (16.67%)  4/57 (7.02%)  4/57 (7.02%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1  2/6 (33.33%)  3/57 (5.26%)  3/57 (5.26%) 
Dry skin * 1  0/6 (0.00%)  1/57 (1.75%)  6/57 (10.53%) 
Periorbital edema * 1  1/6 (16.67%)  0/57 (0.00%)  1/57 (1.75%) 
Pruritus * 1  2/6 (33.33%)  1/57 (1.75%)  4/57 (7.02%) 
Purpura * 1  0/6 (0.00%)  3/57 (5.26%)  1/57 (1.75%) 
Rash acneiform * 1  0/6 (0.00%)  4/57 (7.02%)  4/57 (7.02%) 
Rash maculo-papular * 1  1/6 (16.67%)  5/57 (8.77%)  2/57 (3.51%) 
Skin and subcutaneous tissue disorders - Other * 1  0/6 (0.00%)  5/57 (8.77%)  3/57 (5.26%) 
Vascular disorders       
Hematoma * 1  2/6 (33.33%)  1/57 (1.75%)  1/57 (1.75%) 
Hypertension * 1  3/6 (50.00%)  24/57 (42.11%)  25/57 (43.86%) 
Thromboembolic event * 1  1/6 (16.67%)  2/57 (3.51%)  7/57 (12.28%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Wendy Seiferheld, M.S.
Organization: NRG Oncology
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01609790     History of Changes
Other Study ID Numbers: NCI-2012-01969
NCI-2012-01969 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000734205
S13-00759
RTOG-1122
RTOG-1122 ( Other Identifier: NRG Oncology )
RTOG-1122 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
U10CA021661 ( U.S. NIH Grant/Contract )
First Submitted: May 30, 2012
First Posted: June 1, 2012
Results First Submitted: October 25, 2016
Results First Posted: February 27, 2017
Last Update Posted: June 13, 2019