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Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Recurrent or Progressive Glioblastoma

This study has been terminated.
(Stopped prematurely by Company due to decision to terminate all CTEP supplied drug for further development of RO4929097.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01122901
First received: May 11, 2010
Last updated: March 22, 2017
Last verified: March 2017
Results First Received: November 30, 2016  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: No masking;   Primary Purpose: Treatment
Conditions: Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Recurrent Adult Brain Tumor
Interventions: Drug: gamma-secretase/Notch signalling pathway inhibitor RO4929097
Procedure: therapeutic conventional surgery
Other: pharmacological study
Other: laboratory biomarker analysis

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients enrolled between April 2011 and May 2012 Patients enrolled in outpatient setting

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
Group A RO4929097 PO

Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO QD on days 1-3, 8-10, 15-17, and 22-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

pharmacological study: Correlative studies

Group B RO4929097 Pre Surgery

Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO QD on days -6 to -1. Patients undergo surgical resection on day 0. Within 30 days after surgical resection, patients receive gamma-secretase inhibitor RO4929097 as in group A.

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

therapeutic conventional surgery: Undergo surgery

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies


Participant Flow:   Overall Study
    Group A RO4929097 PO   Group B RO4929097 Pre Surgery
STARTED   40   7 
COMPLETED   40   7 
NOT COMPLETED   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.
No text entered.

Reporting Groups
  Description
Group A RO4929097 PO

Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO QD on days 1-3, 8-10, 15-17, and 22-24. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

pharmacological study: Correlative studies

Group B RO4929097 Pre Surgery

Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO QD on days -6 to -1. Patients undergo surgical resection on day 0. Within 30 days after surgical resection, patients receive gamma-secretase inhibitor RO4929097 as in group A.

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

therapeutic conventional surgery: Undergo surgery

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies

Total Total of all reporting groups

Baseline Measures
   Group A RO4929097 PO   Group B RO4929097 Pre Surgery   Total 
Overall Participants Analyzed 
[Units: Participants]
 40   7   47 
Age 
[Units: Years]
Median (Full Range)
 58 
 (35 to 75) 
 56 
 (43 to 77) 
 57 
 (35 to 77) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      13  32.5%      2  28.6%      15  31.9% 
Male      27  67.5%      5  71.4%      32  68.1% 
Karnofsky Performance Status Scale [1] 
[Units: Units on a scale]
Median (Full Range)
 80 
 (60 to 100) 
 80 
 (60 to 100) 
 80 
 (60 to 100) 
[1] Higher score better 100 normal no complaints/disease 90 capable normal activity few symptoms/disease 80 normal activity, some difficulty some symptoms/signs 70 caring for self not capable normal activity/work 60 requiring some help can take care of most personal requirements 50 requires help often requires frequent medical care 40 disabled requires special care/help 30 severely disabled hospital admission indicated but no risk of death 20 very ill urgently requiring admission requires supportive measures/treatment 10 moribund rapidly progressive fatal disease processes 0 death
Debulking [1] 
[Units: Participants]
Count of Participants
     
Yes   30   6   36 
No   10   1   11 
[1] surgical procedure to remove brain tumor


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Overall Median Progression-free Survival (6-month PFS)   [ Time Frame: At 6 months ]

2.  Primary:   Efficiency of Neurosphere Generation After Pretreatment With RO4929097 (Group B)   [ Time Frame: At time of surgery ]

3.  Secondary:   Radiographic Response Rate According to the Radiographic Assessment in Neuro-Oncology Criteria (Group A) and Group (B)   [ Time Frame: Up to 6 months after completion of treatment ]

4.  Secondary:   Number of Participants With Toxicities Associated With Study Drug (Group A and Group B)   [ Time Frame: Up to 30 days after completion of study treatment ]

5.  Secondary:   Overall Survival   [ Time Frame: 2 years ]

6.  Secondary:   Expression Levels of Notch Pathway Components and Downstream (Group B)   [ Time Frame: At the time of surgery ]

7.  Secondary:   Tumor Propagation (Group B)   [ Time Frame: At the time of surgery ]

8.  Secondary:   Progression Free Survival   [ Time Frame: 2 years ]


  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 terminated prematurely by Company due to their decision to terminate drug supply for further development of this drug. All CTEP-sponsored trials using RO4929097 were closed to accrual and all patients had to be off treatment by 7/31/12.


  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: David Peereboom, MD
Organization: Adult Brain Tumor Consortium
phone: 410-955-8837
e-mail: jfisher@jhmi.edu



Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01122901     History of Changes
Other Study ID Numbers: NCI-2012-02931
NCI-2012-02931 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000672628
ABTC-0906 ( Other Identifier: Adult Brain Tumor Consortium )
ABTC-0906 ( Other Identifier: CTEP )
U01CA137443 ( U.S. NIH Grant/Contract )
Study First Received: May 11, 2010
Results First Received: November 30, 2016
Last Updated: March 22, 2017