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Bevacizumab With or Without Anti-Endoglin Monoclonal Antibody TRC105 in Treating Patients With Recurrent Glioblastoma Multiforme

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ClinicalTrials.gov Identifier: NCT01648348
Recruitment Status : Completed
First Posted : July 24, 2012
Results First Posted : May 23, 2018
Last Update Posted : May 23, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Adult Mixed Glioma
Recurrent Adult Brain Neoplasm
Interventions: Biological: Anti-Endoglin Chimeric Monoclonal Antibody TRC105
Biological: Bevacizumab
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Other: Quality-of-Life Assessment

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Phase I: Bev + TRC105 (Dose 0, Cohort A) Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 (as 3 mg/kg IV) and 11 (as 3 mg/kg IV) of course 1 and days 1 (as 6 mg/kg IV)and 8 (as 6 mg/kg IV) of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Phase I: Bev + TRC105 (Dose 1, Cohort A) Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 (as 3 mg/kg IV) and 11 (as 5 mg/kg IV) of course 1 and days 1 (as 8 mg/kg IV)and 8 (as 8 mg/kg IV) of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Phase I: Bev + TRC105 (Dose 2, Cohort A) Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 (as 3 mg/kg IV) and 11 (as 7 mg/kg IV) of course 1 and days 1 (as 10 mg/kg IV)and 8 (as 10 mg/kg IV) of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Phase I: Bev + TRC105 (Dose 2, Cohort B) Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 (as 3 mg/kg IV) and 11 (as 7 mg/kg IV) of course 1 and days 1 (as 10 mg/kg IV)and 8 (as 10 mg/kg IV) of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Phase II: Bev + TRC105 (Arm I) Experimental: Arm I (bevacizumab and TRC105): Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on day 1 and 10 mg/kg anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Phase II: Bev Alone (Arm II) Active Comparator: Arm II (bevacizumab): Patients receive bevacizumab as in arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Participant Flow:   Overall Study
    Phase I: Bev + TRC105 (Dose 0, Cohort A)   Phase I: Bev + TRC105 (Dose 1, Cohort A)   Phase I: Bev + TRC105 (Dose 2, Cohort A)   Phase I: Bev + TRC105 (Dose 2, Cohort B)   Phase II: Bev + TRC105 (Arm I)   Phase II: Bev Alone (Arm II)
STARTED   5   3   4   3   52   49 
COMPLETED   3   3   3   3   49   43 
NOT COMPLETED   2   0   1   0   3   6 
Cancel                1                0                0                0                3                6 
Replaced for MTD analysis                1                0                1                0                0                0 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Phase I: Bev + TRC105 (Dose 0-2) Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on day 1 and anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 (as 3 mg/kg IV) and 11 (as 3/5/7 mg/kg IV) of course 1 and days 1 (as 6/8/10 mg/kg IV)and 8 (as 6/8/10 mg/kg IV) of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Phase II: Bev + TRC105 (Arm I) Experimental: Arm I (bevacizumab and TRC105): Patients receive 10 mg/kg bevacizumab IV over 30-90 minutes on day 1 and 10 mg/kg anti-endoglin monoclonal antibody TRC105 IV over 1-4 hours on days 8 and 11 of course 1 and days 1 and 8 of all subsequent courses. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Phase II: Bev Alone (Arm II) Active Comparator: Arm II (bevacizumab): Patients receive bevacizumab as in arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Total Total of all reporting groups

Baseline Measures
   Phase I: Bev + TRC105 (Dose 0-2)   Phase II: Bev + TRC105 (Arm I)   Phase II: Bev Alone (Arm II)   Total 
Overall Participants Analyzed 
[Units: Participants]
 15   52   49   116 
Age 
[Units: Years]
Mean (Standard Deviation)
 53.4  (6.6)   56.8  (12.3)   55.6  (10.2)   55.8  (10.8) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      4  26.7%      17  32.7%      12  24.5%      33  28.4% 
Male      11  73.3%      35  67.3%      37  75.5%      83  71.6% 
Region of Enrollment 
[Units: Participants]
       
United States   15   52   49   116 


  Outcome Measures

1.  Primary:   Maximum Tolerated Dose (MTD) (Phase I) as Measured by the Number of Participants With Dose Limiting Toxicities   [ Time Frame: 28 days ]

2.  Primary:   Progression-free Survival (PFS) (Phase II)   [ Time Frame: The time from study randomization to documentation of disease progression, assessed up to 2 years ]

3.  Secondary:   Overall Toxicity Rate for Grade 3 or Higher Adverse Events Considered at Least Possibly Related to Treatment (Phase II)   [ Time Frame: Up to 2 years ]

4.  Secondary:   Overall Survival (Phase II)   [ Time Frame: The time from start of study therapy to death due to any cause, assessed up to 2 years ]

5.  Secondary:   Progression Free Survival at 6 Months (PFS6) (Phase II) as Measured by the Percentage of Participants With Progression Free Survival at 6 Months   [ Time Frame: The time from study randomization to documentation of disease progression, assessed at 6 months ]

6.  Secondary:   Quality of Life (QOL) as Assessed by the EORTC QLQ-C15-PAL Questionnaire [Item 15: Global Health Status/Quality of Life] (Phase II)   [ Time Frame: Baseline and 4 weeks ]

7.  Secondary:   QOL Assessed by EORTC-QLQ-BN20 Patient Questionnaire [Items 1-20] (Phase II)   [ Time Frame: Baseline and 4 weeks ]

8.  Secondary:   QOL Assessed by WIWI Questionnaire (Phase II)   [ Time Frame: Up to 4 weeks ]

9.  Other Pre-specified:   Change in DCE-MRI Utility   [ Time Frame: Baseline to up to 2 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  

10.  Other Pre-specified:   Change in MRI ADC Utility   [ Time Frame: Baseline to up to 2 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  

11.  Other Pre-specified:   Changes in Tumor and Circulating Biomarkers   [ Time Frame: Baseline to up to 2 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.  


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Evanthia Galanis, M.D.
Organization: Mayo Clinic
phone: (507) 284-1370
e-mail: galanis.evanthia@mayo.edu



Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01648348     History of Changes
Other Study ID Numbers: NCI-2012-01989
NCI-2012-01989 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000737109
N1174
NCCTG-N1174
N1174 ( Other Identifier: Alliance for Clinical Trials in Oncology )
N1174 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
U10CA025224 ( U.S. NIH Grant/Contract )
First Submitted: July 20, 2012
First Posted: July 24, 2012
Results First Submitted: September 21, 2017
Results First Posted: May 23, 2018
Last Update Posted: May 23, 2018