RO4929097and Bevacizumab in Treating Patients With Progressive or Recurrent Malignant Glioma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01189240
First received: August 25, 2010
Last updated: June 22, 2015
Last verified: June 2015
Results First Received: May 5, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Adult Anaplastic Astrocytoma
Adult Anaplastic Oligodendroglioma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Interventions: Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097
Biological: bevacizumab
Other: laboratory biomarker analysis
Other: pharmacological study

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Phase I trial started 8/2011 and enrollment closed 7/31/12. 13 total patients treated by RO4929097 (5, 10, 20mg/kg) in combo with bevacizumab. 1 treated pt ineligible for study. Analysis data for toxicity included 13 treated pts. Analytical dataset results other than toxicity included 12 eligible pts only. Pts enrolled from outpt medical clinics

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 Dose Finding - Level 1 5mg

Patients receive oral gamma-secretase/Notch signalling pathway inhibitor RO49290977 5mg on days 1-3, 8-10, 15-17, and 22-24, and bevacizumab IV over 30-90 minutes on days 1 and 15. Other: blood samples for pharmacological study; archived tumor tissue slides for laboratory biomarker analysis.

gamma-secretase/Notch signalling pathway inhibitor RO4929097: Given orally

bevacizumab: Given IV

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

Phase I Dose Finding Level 2 10mg

Patients receive oral gamma-secretase/Notch signalling pathway inhibitor RO49290977 10mg on days 1-3, 8-10, 15-17, and 22-24, and bevacizumab IV over 30-90 minutes on days 1 and 15. Other: blood samples for pharmacological study; archived tumor tissue slides for laboratory biomarker analysis.

gamma-secretase/Notch signalling pathway inhibitor RO4929097: Given orally

bevacizumab: Given IV

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies

Phase I Dose Finding Level 3 20mg

Patients receive oral gamma-secretase/Notch signalling pathway inhibitor RO49290977 20mg on days 1-3, 8-10, 15-17, and 22-24, and bevacizumab IV over 30-90 minutes on days 1 and 15. Other: blood samples for pharmacological study; archived tumor tissue slides for laboratory biomarker analysis.

gamma-secretase/Notch signalling pathway inhibitor RO4929097: Given orally

bevacizumab: Given IV

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies


Participant Flow:   Overall Study
    Phase I Dose Finding - Level 1 5mg     Phase I Dose Finding Level 2 10mg     Phase I Dose Finding Level 3 20mg  
STARTED     4     6     3  
COMPLETED     4     6     3  
NOT COMPLETED     0     0     0  



  Baseline Characteristics
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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.
1 pt not eligible for study and hence was not included in the analytical analysis

Reporting Groups
  Description
Phase I Dose Finding

Patients receive oral gamma-secretase/Notch signalling pathway inhibitor RO49290977 on days 1-3, 8-10, 15-17, and 22-24, and bevacizumab IV over 30-90 minutes on days 1 and 15. Other: blood samples for pharmacological study; archived tumor tissue slides for laboratory biomarker analysis.

gamma-secretase/Notch signalling pathway inhibitor RO4929097: Given orally

bevacizumab: Given IV

laboratory biomarker analysis: Correlative studies

pharmacological study: Correlative studies


Baseline Measures
    Phase I Dose Finding  
Number of Participants  
[units: participants]
  12  
Age  
[units: years]
Median (Full Range)
  56   (42 to 62)  
Gender  
[units: participants]
 
Female     7  
Male     5  
Race/Ethnicity, Customized  
[units: participants]
 
African American     2  
White     10  
Karnofsky Performance Status [1]
[units: participants]
 
90     6  
80     5  
70     0  
60     1  
Mini Mental State Examination (MMSE) [2]
[units: units on a scale]
Median (Full Range)
  29   (21 to 30)  
Prior Relapses  
[units: participants]
 
1 relapse     8  
2 relapes     3  
3 relapses     1  
Initial Procedure  
[units: participants]
 
biopsy     1  
Resection     11  
Initial Histological Diagnosis  
[units: participants]
 
Glioblastoma     10  
Other     2  
[1]

100-80: Able to carry on normal activity and to work; No special care needed.

70-50: Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed.

40-10: Unable to care for self; Requires equivalent of institutional or hospital care;diseases may be progressing rapidly.

0: Dead

[2]

Measure of Cognitive impairment

24-30 No cognitive impairment 18-23 Mild cognitive impairment 0-17 Severe cognitive impairment

Series of questions with a point value for each question which is summed to give a total final score.




  Outcome Measures

1.  Primary:   Maximum-tolerated Dose and the Recommended Phase II Dose of Gamma-secretase Inhibitor RO4929097 in Combination With Bevacizumab Determined by Dose-limiting Toxicity Rate (Phase I)   [ Time Frame: 28 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
Study closed prematurely by Roche as study was in final cohort level 3, 20mg/kg & to enroll 3 more pts to confirm MTD. Roche halted pt enrollment in all clinical trials with RO4929097 and cease production of drug & development of this agent.


  More Information
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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: Dr. Edward Pan
Organization: Adult Brain Tumor Consortium (ABTC)
e-mail: Edward.Pan@UTSouthwestern.edu


No publications provided


Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01189240     History of Changes
Other Study ID Numbers: NCI-2011-02509, NCI-2011-02509, CDR0000683099, ABTC-1002, ABTC-1002, U01CA137443
Study First Received: August 25, 2010
Results First Received: May 5, 2015
Last Updated: June 22, 2015
Health Authority: United States: Food and Drug Administration