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Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor

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ClinicalTrials.gov Identifier: NCT01404650
Recruitment Status : Completed
First Posted : July 28, 2011
Results First Posted : October 4, 2016
Last Update Posted : October 4, 2016
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gastrointestinal Stromal Tumor
Intervention Drug: AUY922
Enrollment 25
Recruitment Details This multi-center trial evaluated AUY922 monotherapy as treatment for patients with gastrointestinal stromal tumor (GIST) refractory to, or intolerant of, imatinib and sunitinib. Between Dec 2011 and Jan 2015, 25 patients enrolled in the trial. Thirty-four patients (34) were planned to be enrolled but enrollment stopped early due to slow accrual.
Pre-assignment Details  
Arm/Group Title AUY922
Hide Arm/Group Description AUY922: 70 mg/m2 IV over 60 minutes on Days 1, 8, and 15 of each cycle. Treatment cycles repeated every 21 days. Patients are evaluated for response at 6 and 12 weeks and then every 9 weeks (i.e., every 3 cycles) thereafter until evidence of disease progression or intolerable toxicity.
Period Title: Overall Study
Started 25 [1]
Completed 25
Not Completed 0
[1]
Twenty-five patients received a median of 2 cycles of AUY922.
Arm/Group Title AUY922
Hide Arm/Group Description AUY922: 70 mg/m2 IV over 60 minutes on Days 1, 8, and 15 of each cycle. Treatment cycles repeated every 21 days. Patients are evaluated for response at 6 and 12 weeks and then every 9 weeks (i.e., every 3 cycles) thereafter until evidence of disease progression or intolerable toxicity.
Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
<=18 years
0
   0.0%
Between 18 and 65 years
16
  64.0%
>=65 years
9
  36.0%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 25 participants
63
(20 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
11
  44.0%
Male
14
  56.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
5
  20.0%
White
20
  80.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 25 participants
25
1.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description Measured from time of randomization until objective tumor progression or death; assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Progressive disease (PD) defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest (nadir) sum since the treatment started, or the appearance of one or more new lesions.
Time Frame At 6 and 12 weeks then every 9 weeks thereafter until progression or intolerable toxicity, up to 4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title AUY922
Hide Arm/Group Description:
AUY922: 70 mg/m2 IV over 60 minutes on Days 1, 8, and 15 of each cycle. Treatment cycles repeated every 21 days. Patients are evaluated for response at 6 and 12 weeks and then every 9 weeks (i.e., every 3 cycles) thereafter until evidence of disease progression or intolerable toxicity.
Overall Number of Participants Analyzed 25
Median (95% Confidence Interval)
Unit of Measure: months
3.9
(2.5 to 5.3)
2.Secondary Outcome
Title Response Rate (RR)
Hide Description Defined as the proportion of complete and partial responses, assessed per RECIST v1.1. Complete response (CR) defined as a disappearance of all lesions; partial response (PR) defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking the baseline sum LD as reference. Stable Disease (SD) defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for progressive disease, taking as reference the smallest (nadir) sum LD since start of treatment.
Time Frame At 6 and 12 weeks then every 9 weeks thereafter until progressive disease or intolerable toxicity, for up to 4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Of 25 patients enrolled, 4 patients were not evaluable for response due to treatment discontinuation prior to first disease evaluation.
Arm/Group Title AUY922
Hide Arm/Group Description:
AUY922: 70 mg/m2 IV over 60 minutes on Days 1, 8, and 15 of each cycle. Treatment cycles repeated every 21 days. Patients are evaluated for response at 6 and 12 weeks and then every 9 weeks (i.e., every 3 cycles) thereafter until evidence of disease progression or intolerable toxicity.
Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: percentage of participants
Stable Disease 60
Objective Response 4
Progressive Disease 20
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description Evidence of survival was obtained by clinic visit or telephone contact from the time of first dose until death from any cause.
Time Frame Every 3 months until patient death or lost to follow-up, for up to 4 years.
Hide Outcome Measure Data
Hide Analysis Population Description
All 25 patients who received treatment were included in the analysis of overall survival.
Arm/Group Title AUY922
Hide Arm/Group Description:
AUY922: 70 mg/m2 IV over 60 minutes on Days 1, 8, and 15 of each cycle. Treatment cycles repeated every 21 days. Patients are evaluated for response at 6 and 12 weeks and then every 9 weeks (i.e., every 3 cycles) thereafter until evidence of disease progression or intolerable toxicity.
Overall Number of Participants Analyzed 25
Median (95% Confidence Interval)
Unit of Measure: months
8.5
(5.2 to 16.7)
4.Secondary Outcome
Title Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Hide Description Worst toxicity grades per patient were tabulated for select adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 4.0
Time Frame Days 1, 8 and 15 of each 21-day cycle plus 30 days after treatment discontinuation.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study drug.
Arm/Group Title AUY922
Hide Arm/Group Description:
AUY922: 70 mg/m2 IV over 60 minutes on Days 1, 8, and 15 of each cycle. Treatment cycles repeated every 21 days. Patients are evaluated for response at 6 and 12 weeks and then every 9 weeks (i.e., every 3 cycles) thereafter until evidence of disease progression or intolerable toxicity.
Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: participants
Anemia 10
Leukopenia 1
Thrombocytopenia 1
Diarrhea 16
Fatigue 13
Nausea 11
Vomiting 7
Asthenia 5
Abdominal Pain 3
Headache 3
Pain 3
Alkaline phosphatase increased 2
Anorexia 2
Dehydration 2
Dysgeusia 2
Blurred vision 9
Flashing lights 7
Delayed light/darl adaptation 4
Night Blindness 3
Floaters 2
Decreased color perception 2
Light sensitivity 4
Vision darkening 2
Vision change NOS 3
Time Frame Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
Adverse Event Reporting Description Patients were permitted to continue treatment in the absence of disease progression or intolerable toxicity. 25 patients received a median of 2 cycles (6 weeks) of treatment
 
Arm/Group Title AUY922
Hide Arm/Group Description AUY922: 70 mg/m2 IV over 60 minutes on Days 1, 8, and 15 of each cycle. Treatment cycles repeated every 21 days. Patients are evaluated for response at 6 and 12 weeks and then every 9 weeks (i.e., every 3 cycles) thereafter until evidence of disease progression or intolerable toxicity.
All-Cause Mortality
AUY922
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
AUY922
Affected / at Risk (%) # Events
Total   8/25 (32.00%)    
Cardiac disorders   
Chest pain  1  1/25 (4.00%)  1
Gastrointestinal disorders   
Gastrointestinal hemmorhage  1  3/25 (12.00%)  4
Intestinal obstruction  1  2/25 (8.00%)  2
Abdominal pain  1  1/25 (4.00%)  1
Infections and infestations   
Bacteraemia  1  1/25 (4.00%)  1
Septic shock  1  1/25 (4.00%)  1
Injury, poisoning and procedural complications   
Feeding tube complication  1  1/25 (4.00%)  1
Psychiatric disorders   
Confusional state  1  1/25 (4.00%)  1
Respiratory, thoracic and mediastinal disorders   
Pulmonary embolism  1  1/25 (4.00%)  1
Vascular disorders   
Haemorrhage  1  1/25 (4.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, NCI CTCAE 4.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AUY922
Affected / at Risk (%) # Events
Total   25/25 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  10/25 (40.00%) 
Eye disorders   
Blurred vision  1  9/25 (36.00%) 
Flashing lights  1  7/25 (28.00%) 
Delayed light/dark adaptation  1  4/25 (16.00%) 
Decreased color perception  1  2/25 (8.00%) 
Night blindness  1  3/25 (12.00%) 
Floaters  1  2/25 (8.00%) 
Light sensitivity  1  4/25 (16.00%) 
vision change NOS  1 [1]  3/25 (12.00%) 
Vision darkening  1  2/25 (8.00%) 
Gastrointestinal disorders   
Abdominal pain  1  3/25 (12.00%) 
Constipation  1  3/25 (12.00%) 
Nausea  1  11/25 (44.00%) 
Diarrhea  1  16/25 (64.00%) 
Vomiting  1  7/25 (28.00%) 
Anorexia  1  2/25 (8.00%) 
General disorders   
Fatigue  1  13/25 (52.00%) 
Investigations   
Alkaline phosphatase increased  1  2/25 (8.00%) 
Metabolism and nutrition disorders   
Dehydration  1  2/25 (8.00%) 
Musculoskeletal and connective tissue disorders   
Asthenia  1  5/25 (20.00%) 
Nervous system disorders   
Headache  1  3/25 (12.00%) 
Pain  1  3/25 (12.00%) 
Dysgeusia  1  2/25 (8.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, NCI CTCAE 4.0
[1]
NOS=not otherwise specified
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 sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
Results Point of Contact
Name/Title: Johanna Bendell, MD
Organization: Sarah Cannon Research Institute
Phone: 877-691-7274
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01404650     History of Changes
Other Study ID Numbers: SCRI GI 148
First Submitted: July 21, 2011
First Posted: July 28, 2011
Results First Submitted: May 13, 2016
Results First Posted: October 4, 2016
Last Update Posted: October 4, 2016