Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT01154452
Recruitment Status : Completed
First Posted : June 30, 2010
Results First Posted : July 22, 2016
Last Update Posted : August 15, 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 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
Enrollment 78
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 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
Hide Arm/Group Description RO4929097: 10mg PO QD, GDC-0449: 150 mg PO QD RO4929097: 15 mg PO QD, GDC-0449: 150 mg PO QD ARM 1 - RO4929097: 15 mg PO QD ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
Period Title: Phase Ib
Started 6 4 0 0
Completed 3 3 0 0
Not Completed 3 1 0 0
Reason Not Completed
Not Treated             1             0             0             0
Adverse Event             2             1             0             0
Period Title: Phase II
Started 0 0 35 33
Completed 0 0 30 27
Not Completed 0 0 5 6
Reason Not Completed
Withdrawal by Subject             0             0             1             2
Adverse Event             0             0             4             4
Arm/Group Title 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
Hide Arm/Group Description RO4929097: 10mg PO QD, GDC-0449: 150 mg PO QD RO4929097: 15 mg PO QD, GDC-0449: 150 mg PO QD ARM 1 - RO4929097: 15 mg PO QD ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD Total of all reporting groups
Overall Number of Baseline Participants 6 4 35 33 78
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 4 participants 35 participants 33 participants 78 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6
 100.0%
3
  75.0%
25
  71.4%
27
  81.8%
61
  78.2%
>=65 years
0
   0.0%
1
  25.0%
10
  28.6%
6
  18.2%
17
  21.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 4 participants 35 participants 33 participants 78 participants
Female
2
  33.3%
2
  50.0%
15
  42.9%
15
  45.5%
34
  43.6%
Male
4
  66.7%
2
  50.0%
20
  57.1%
18
  54.5%
44
  56.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants 4 participants 35 participants 33 participants 78 participants
6 4 35 33 78
1.Primary Outcome
Title 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)
Hide Description [Not Specified]
Time Frame Up to 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Phase Ib Participants
Hide Arm/Group Description:
All Phase Ib Participants
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: mg
15
2.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description Progression-free survival (PFS) of the combination of RO4929097 with and without GDC-0449 in patients with advanced sarcoma. (Phase II)
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I (Gamma-secretase Inhibitor RO4929097) Arm II (Vismodegib and Gamma-secretase Inhibitor RO4929097)
Hide Arm/Group Description:

Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO QD on days 1-21.

Gamma-Secretase Inhibitor RO4929097: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Patients receive vismodegib PO and gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO QD on days 1-21.

Gamma-Secretase Inhibitor RO4929097: Given PO

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Vismodegib: Given PO
Overall Number of Participants Analyzed 35 33
Measure Type: Number
Unit of Measure: percentage of participants
60 60
3.Secondary Outcome
Title Response Rate (CR + PR) as Assessed by RECIST 1.1 (Phase Ib and II)
Hide Description Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions
Time Frame Up to 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 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
Hide Arm/Group Description:
RO4929097: 10mg PO QD, GDC-0449: 150 mg PO QD
RO4929097: 15 mg PO QD, GDC-0449: 150 mg PO QD
ARM 1 - RO4929097: 15 mg PO QD
ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
Overall Number of Participants Analyzed 3 3 30 27
Measure Type: Number
Unit of Measure: participants
Stable Disease 2 2 17 16
Progression of Disease 1 1 13 11
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 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
Hide Arm/Group Description RO4929097: 10mg PO QD, GDC-0449: 150 mg PO QD RO4929097: 15 mg PO QD, GDC-0449: 150 mg PO QD ARM 1 - RO4929097: 15 mg PO QD ARM 2: GDC-0449 150 mg PO QD and RO4929097 15 mg PO QD
All-Cause Mortality
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
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
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/6 (33.33%)      2/4 (50.00%)      11/35 (31.43%)      8/33 (24.24%)    
Blood and lymphatic system disorders         
Anemia † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 2/35 (5.71%)  2 1/33 (3.03%)  1
Gastrointestinal disorders         
Dysphagia † 1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/35 (0.00%)  0 0/33 (0.00%)  0
Small intestinal obstruction † 1  0/6 (0.00%)  0 1/4 (25.00%)  1 1/35 (2.86%)  1 0/33 (0.00%)  0
Abdominal pain † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 1/33 (3.03%)  1
Constipation † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 0/35 (0.00%)  0 1/33 (3.03%)  1
Retroperitoneal hemorrhage † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 0/35 (0.00%)  0 1/33 (3.03%)  1
Vomiting † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 0/35 (0.00%)  0 1/33 (3.03%)  1
General disorders         
Death NOS † 1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/35 (0.00%)  0 0/33 (0.00%)  0
Multi-organ failure † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
Pain † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
Infections and infestations         
Urinary tract infection † 1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/35 (0.00%)  0 0/33 (0.00%)  0
Wound infection † 1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/35 (0.00%)  0 0/33 (0.00%)  0
Lung infection † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
Prostate infection † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
Sepsis † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
Sinusitis † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
Skin infection † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
Investigations         
Lymphocyte count decreased † 1  1/6 (16.67%)  1 1/4 (25.00%)  1 2/35 (5.71%)  3 0/33 (0.00%)  0
Alanine aminotransferase increased † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 2/35 (5.71%)  2 0/33 (0.00%)  0
Alkaline phosphatase increased † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
Aspartate aminotransferase increased † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
Metabolism and nutrition disorders         
Hypophosphatemia † 1  1/6 (16.67%)  1 1/4 (25.00%)  2 0/35 (0.00%)  0 0/33 (0.00%)  0
Hyponatremia † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 0/35 (0.00%)  0 1/33 (3.03%)  1
Musculoskeletal and connective tissue disorders         
Neck pain † 1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/35 (0.00%)  0 0/33 (0.00%)  0
Pain in extremity † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Treatment related secondary malignancy † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 0/35 (0.00%)  0 1/33 (3.03%)  1
Tumor pain † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 0/35 (0.00%)  0 2/33 (6.06%)  2
Respiratory, thoracic and mediastinal disorders         
Pleuritic pain † 1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/35 (0.00%)  0 0/33 (0.00%)  0
Pleural effusion † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
Resp, thoracic & mediastinal disorder Other, spec † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
Vascular disorders         
Thromboembolic event † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 1/35 (2.86%)  1 0/33 (0.00%)  0
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/6 (66.67%)      4/4 (100.00%)      26/35 (74.29%)      23/33 (69.70%)    
Blood and lymphatic system disorders         
Anemia † 1  1/6 (16.67%)  12 3/4 (75.00%)  42 11/35 (31.43%)  56 8/33 (24.24%)  32
Eye disorders         
Blurred vision † 1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/35 (0.00%)  0 0/33 (0.00%)  0
Gastrointestinal disorders         
Constipation † 1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/35 (0.00%)  0 1/33 (3.03%)  1
Nausea † 1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/35 (0.00%)  0 3/33 (9.09%)  4
Dysgeusia † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 0/35 (0.00%)  0 2/33 (6.06%)  2
General disorders         
Fatigue † 1  0/6 (0.00%)  0 2/4 (50.00%)  3 0/35 (0.00%)  0 2/33 (6.06%)  2
Investigations         
Activated partial thromboplastin time prolonged † 1  1/6 (16.67%)  1 1/4 (25.00%)  2 0/35 (0.00%)  0 0/33 (0.00%)  0
Lymphocyte count decreased † 1  2/6 (33.33%)  3 3/4 (75.00%)  12 6/35 (17.14%)  32 2/33 (6.06%)  5
Neutrophil count decreased † 1  1/6 (16.67%)  2 1/4 (25.00%)  1 1/35 (2.86%)  1 2/33 (6.06%)  3
White blood cell decreased † 1  1/6 (16.67%)  1 1/4 (25.00%)  1 3/35 (8.57%)  3 1/33 (3.03%)  3
Alanine aminotransferase increased † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 3/35 (8.57%)  6 2/33 (6.06%)  2
Blood bilirubin increased † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 2/35 (5.71%)  3 0/33 (0.00%)  0
Alkaline phosphatase increased † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 3/35 (8.57%)  20 2/33 (6.06%)  6
Aspartate aminotransferase increased † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 3/35 (8.57%)  7 1/33 (3.03%)  1
CPK increased † 1  0/6 (0.00%)  0 0/4 (0.00%)  0 0/35 (0.00%)  0 2/33 (6.06%)  3
Metabolism and nutrition disorders         
Hypercalcemia † 1  1/6 (16.67%)  1 0/4 (0.00%)  0 0/35 (0.00%)  0 0/33 (0.00%)  0
Hyperglycemia † 1  1/6 (16.67%)  1 2/4 (50.00%)  4 6/35 (17.14%)  34 5/33 (15.15%)  10
Hypoalbuminemia † 1  1/6 (16.67%)  11 3/4 (75.00%)  18 9/35 (25.71%)  21 4/33 (12.12%)  16
Hypocalcemia † 1  2/6 (33.33%)  13 1/4 (25.00%)  2 7/35 (20.00%)  13 1/33 (3.03%)  3
Hypokalemia † 1  1/6 (16.67%)  2 1/4 (25.00%)  1 0/35 (0.00%)  0 1/33 (3.03%)  1
Hyponatremia † 1  1/6 (16.67%)  1 1/4 (25.00%)  1 1/35 (2.86%)  1 0/33 (0.00%)  0
Hypophosphatemia † 1  1/6 (16.67%)  4 3/4 (75.00%)  26 14/35 (40.00%)  50 12/33 (36.36%)  26
Anorexia † 1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/35 (0.00%)  0 0/33 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Musculoskeletal & conn tissue disorder Other, spec † 1  1/6 (16.67%)  3 0/4 (0.00%)  0 1/35 (2.86%)  2 2/33 (6.06%)  2
Muscle weakness upper limb † 1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/35 (0.00%)  0 0/33 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Pleuritic pain † 1  0/6 (0.00%)  0 1/4 (25.00%)  1 0/35 (0.00%)  0 0/33 (0.00%)  0
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Roche has discontinued further development of the Notch inhibitor (RO4929097) and this Phase II trial was prematurely closed.
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
Layout table for Results Point of Contact information
Name/Title: Dr. Mrinal Gounder
Organization: Memorial Sloan Kettering Cancer Center
Phone: 646-888-4167
EMail: gounderm@mskcc.org
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01154452    
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 ( U.S. NIH Grant/Contract )
P30CA008748 ( U.S. NIH Grant/Contract )
U01CA069856 ( U.S. NIH Grant/Contract )
First Submitted: June 29, 2010
First Posted: June 30, 2010
Results First Submitted: March 18, 2016
Results First Posted: July 22, 2016
Last Update Posted: August 15, 2018