Trial Outcomes & Findings for Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor (NCT NCT01404650)
NCT ID: NCT01404650
Last Updated: 2016-10-04
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
At 6 and 12 weeks then every 9 weeks thereafter until progression or intolerable toxicity, up to 4 years.
Results posted on
2016-10-04
Participant Flow
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.
Participant milestones
| Measure |
AUY922
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 Study
STARTED
|
25
|
|
Overall Study
COMPLETED
|
25
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of Hsp90 Inhibitor AUY922 for the Treatment of Patients With Refractory Gastrointestinal Stromal Tumor
Baseline characteristics by cohort
| Measure |
AUY922
n=25 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=99 Participants
|
|
Age, Continuous
|
63 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
25 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: At 6 and 12 weeks then every 9 weeks thereafter until progression or intolerable toxicity, up to 4 years.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.
Outcome measures
| Measure |
AUY922
n=25 Participants
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.
|
|---|---|
|
Progression-free Survival (PFS)
|
3.9 months
Interval 2.5 to 5.3
|
SECONDARY outcome
Timeframe: At 6 and 12 weeks then every 9 weeks thereafter until progressive disease or intolerable toxicity, for up to 4 years.Population: Of 25 patients enrolled, 4 patients were not evaluable for response due to treatment discontinuation prior to first disease evaluation.
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.
Outcome measures
| Measure |
AUY922
n=21 Participants
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.
|
|---|---|
|
Response Rate (RR)
Stable Disease
|
60 percentage of participants
|
|
Response Rate (RR)
Objective Response
|
4 percentage of participants
|
|
Response Rate (RR)
Progressive Disease
|
20 percentage of participants
|
SECONDARY outcome
Timeframe: Every 3 months until patient death or lost to follow-up, for up to 4 years.Population: All 25 patients who received treatment were included in the analysis of overall survival.
Evidence of survival was obtained by clinic visit or telephone contact from the time of first dose until death from any cause.
Outcome measures
| Measure |
AUY922
n=25 Participants
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 Survival (OS)
|
8.5 months
Interval 5.2 to 16.7
|
SECONDARY outcome
Timeframe: Days 1, 8 and 15 of each 21-day cycle plus 30 days after treatment discontinuation.Population: All participants who received at least one dose of study drug.
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
Outcome measures
| Measure |
AUY922
n=25 Participants
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.
|
|---|---|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Anemia
|
10 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Leukopenia
|
1 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Thrombocytopenia
|
1 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Diarrhea
|
16 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Fatigue
|
13 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Nausea
|
11 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Vomiting
|
7 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Asthenia
|
5 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Abdominal Pain
|
3 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Headache
|
3 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Pain
|
3 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Alkaline phosphatase increased
|
2 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Anorexia
|
2 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Dehydration
|
2 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Dysgeusia
|
2 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Blurred vision
|
9 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Flashing lights
|
7 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Delayed light/darl adaptation
|
4 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Night Blindness
|
3 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Floaters
|
2 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Decreased color perception
|
2 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Light sensitivity
|
4 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Vision darkening
|
2 participants
|
|
Number of Patients With Adverse Events as a Measure of Safety and Tolerability
Vision change NOS
|
3 participants
|
Adverse Events
AUY922
Serious events: 8 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AUY922
n=25 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Gastrointestinal hemmorhage
|
12.0%
3/25 • Number of events 4 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Gastrointestinal disorders
Intestinal obstruction
|
8.0%
2/25 • Number of events 2 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Vascular disorders
Haemorrhage
|
4.0%
1/25 • Number of events 1 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Infections and infestations
Bacteraemia
|
4.0%
1/25 • Number of events 1 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Injury, poisoning and procedural complications
Feeding tube complication
|
4.0%
1/25 • Number of events 1 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
4.0%
1/25 • Number of events 1 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Infections and infestations
Septic shock
|
4.0%
1/25 • Number of events 1 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Psychiatric disorders
Confusional state
|
4.0%
1/25 • Number of events 1 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Gastrointestinal disorders
Abdominal pain
|
4.0%
1/25 • Number of events 1 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Cardiac disorders
Chest pain
|
4.0%
1/25 • Number of events 1 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
Other adverse events
| Measure |
AUY922
n=25 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
12.0%
3/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Gastrointestinal disorders
Constipation
|
12.0%
3/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Gastrointestinal disorders
Nausea
|
44.0%
11/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Gastrointestinal disorders
Diarrhea
|
64.0%
16/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Gastrointestinal disorders
Vomiting
|
28.0%
7/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
General disorders
Fatigue
|
52.0%
13/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Investigations
Alkaline phosphatase increased
|
8.0%
2/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Musculoskeletal and connective tissue disorders
Asthenia
|
20.0%
5/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Eye disorders
Blurred vision
|
36.0%
9/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Eye disorders
Flashing lights
|
28.0%
7/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Eye disorders
Delayed light/dark adaptation
|
16.0%
4/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Eye disorders
Decreased color perception
|
8.0%
2/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Nervous system disorders
Headache
|
12.0%
3/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Blood and lymphatic system disorders
Anemia
|
40.0%
10/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Nervous system disorders
Pain
|
12.0%
3/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Gastrointestinal disorders
Anorexia
|
8.0%
2/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Metabolism and nutrition disorders
Dehydration
|
8.0%
2/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Nervous system disorders
Dysgeusia
|
8.0%
2/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Eye disorders
Night blindness
|
12.0%
3/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Eye disorders
Floaters
|
8.0%
2/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Eye disorders
Light sensitivity
|
16.0%
4/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Eye disorders
vision change NOS
|
12.0%
3/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
|
Eye disorders
Vision darkening
|
8.0%
2/25 • Adverse events collected on Days 1, 8 and 15 of each 21-day cycle and up to 30 days post-treatment.
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
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER