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Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01154452
First received: June 29, 2010
Last updated: June 9, 2016
Last verified: April 2016
Results First Received: March 18, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Adult Alveolar Soft Part Sarcoma
Adult Angiosarcoma
Adult Desmoplastic Small Round Cell Tumor
Adult Epithelioid Hemangioendothelioma
Adult Epithelioid Sarcoma
Adult Extraskeletal Myxoid Chondrosarcoma
Adult Extraskeletal Osteosarcoma
Adult Fibrosarcoma
Adult Leiomyosarcoma
Adult Liposarcoma
Adult Malignant Mesenchymoma
Adult Malignant Peripheral Nerve Sheath Tumor
Adult Rhabdomyosarcoma
Adult Synovial Sarcoma
Adult Unclassified Pleomorphic Sarcoma
Chondrosarcoma
Clear Cell Sarcoma of the Kidney
Conjunctival Kaposi Sarcoma
Dermatofibrosarcoma Protuberans
Gastrointestinal Stromal Tumor
Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Metastatic Osteosarcoma
Ovarian Sarcoma
Recurrent Adult Soft Tissue Sarcoma
Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone
Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Recurrent Kaposi Sarcoma
Recurrent Osteosarcoma
Recurrent Uterine Corpus Sarcoma
Small Intestine Leiomyosarcoma
Stage III Adult Soft Tissue Sarcoma
Stage III Uterine Sarcoma
Stage IV Adult Soft Tissue Sarcoma
Stage IV Uterine Sarcoma
Unclassified Pleomorphic Sarcoma of Bone
Interventions: Drug: Gamma-Secretase Inhibitor RO4929097
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Vismodegib

  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
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
RO4929097 10mg RO4929097: 10mg PO QD, GDC-0449: 150 mg PO QD
RO4929097 15 mg RO4929097: 15 mg PO QD, GDC-0449: 150 mg PO QD
ARM 1 - RO4929097: 15 mg PO QD ARM 1 - RO4929097: 15 mg PO QD
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD

Participant Flow for 2 periods

Period 1:   Phase Ib
    RO4929097 10mg     RO4929097 15 mg     ARM 1 - RO4929097: 15 mg PO QD     ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD  
STARTED     6     4     0     0  
COMPLETED     3     3     0     0  
NOT COMPLETED     3     1     0     0  
Not Treated                 1                 0                 0                 0  
Adverse Event                 2                 1                 0                 0  

Period 2:   Phase II
    RO4929097 10mg     RO4929097 15 mg     ARM 1 - RO4929097: 15 mg PO QD     ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD  
STARTED     0     0     35     33  
COMPLETED     0     0     30     27  
NOT COMPLETED     0     0     5     6  
Withdrawal by Subject                 0                 0                 1                 2  
Adverse Event                 0                 0                 4                 4  



  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
RO4929097 10mg RO4929097: 10mg PO QD, GDC-0449: 150 mg PO QD
RO4929097 15 mg RO4929097: 15 mg PO QD, GDC-0449: 150 mg PO QD
ARM 1 - RO4929097: 15 mg PO QD ARM 1 - RO4929097: 15 mg PO QD
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
Total Total of all reporting groups

Baseline Measures
    RO4929097 10mg     RO4929097 15 mg     ARM 1 - RO4929097: 15 mg PO QD     ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD     Total  
Number of Participants  
[units: participants]
  6     4     35     33     78  
Age  
[units: participants]
         
<=18 years     0     0     0     0     0  
Between 18 and 65 years     6     3     25     27     61  
>=65 years     0     1     10     6     17  
Gender  
[units: participants]
         
Female     2     2     15     15     34  
Male     4     2     20     18     44  
Region of Enrollment  
[units: participants]
         
United States     6     4     35     33     78  



  Outcome Measures
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1.  Primary:   Maximum-tolerated Dose of Gamma-secretase Inhibitor RO4929097, Defined as the Dose Level Where no More Than 1 Out of 6 Patients Experience DLT at the Highest Dose Level Below the MAD, Graded According to NCI-CTCAE Version 4.0 (Phase Ib)   [ Time Frame: Up to 28 days ]

2.  Secondary:   Response Rate (CR + PR) as Assessed by RECIST 1.1 (Phase Ib and II)   [ Time Frame: Up to 4 months ]

3.  Primary:   Progression-free Survival (PFS) of the Combination of RO4929097 With and Without GDC-0449 in Patients With Advanced Sarcoma. (Phase II)   [ Time Frame: 1 year ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  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
Roche has discontinued further development of the Notch inhibitor (RO4929097) and this Phase II trial was prematurely closed.


  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. Mrinal Gounder
Organization: Memorial Sloan Kettering Cancer Center
phone: 646-888-4167
e-mail: gounderm@mskcc.org



Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01154452     History of Changes
Other Study ID Numbers: NCI-2011-01412
NCI-2011-01412 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000680558
MSKCC-10049
10-049 ( Other Identifier: Memorial Sloan-Kettering Cancer Center )
8406 ( Other Identifier: CTEP )
N01CM62206 ( US NIH Grant/Contract Award Number )
P30CA008748 ( US NIH Grant/Contract Award Number )
U01CA069856 ( US NIH Grant/Contract Award Number )
Study First Received: June 29, 2010
Results First Received: March 18, 2016
Last Updated: June 9, 2016
Health Authority: United States: Food and Drug Administration