Description:
A Phase II Study of AUY922, Novel HSP Inhibitor, in Patients with Advanced GIST Failed to or
Intolerance of Imatinib and Sunitinib Therapy
Primary endpoint:
•The primary endpoint of this study is to assess disease control rate (complete response +
partial response + stable disease≧4 months) of AUY922 in patients with advanced GIST failed
to imatinib and sunitinib
Secondary endpoints:
- To determinate the objective response rate (ORR, complete response + partial response)
- To determinate the time to tumor progression (TTP)
- To evaluate the safety and toxicity profiles of AUY922
- To evaluate the pharmacokinetics profile of AUY922 in Taiwan GIST population
- To access the pharmacodynamic effect of AUY922 on HSP client proteins in blood and tumor
if feasible , i.e. HSP70, in Taiwan GIST population
- To access the tissue biomarkers pre-treatment and 4wks post treatment if feasible, i.e.
HSP70, c-KIT, PDGFRA mutation, ...etc in Taiwan GIST population
Exploratory endpoints:
•PET imaging; sSUVmax
Title
- Brief Title: A Study of AUY922 for GIST(Gastrointestinal Stromal Tumor) Patients
- Official Title: A Phase II Study of AUY922, a Novel HSP Inhibitor, in Patients With Advanced GIST Failed to or Intolerance of Imatinib and Sunitinib Therapy
Clinical Trial IDs
- ORG STUDY ID:
T2211
- NCT ID:
NCT01389583
Conditions
- Gastrointestinal Stromal Tumor
Interventions
Drug | Synonyms | Arms |
---|
AUY922 | | AUY922 |
Purpose
A Phase II Study of AUY922, Novel HSP Inhibitor, in Patients with Advanced GIST Failed to or
Intolerance of Imatinib and Sunitinib Therapy
Primary endpoint:
•The primary endpoint of this study is to assess disease control rate (complete response +
partial response + stable disease≧4 months) of AUY922 in patients with advanced GIST failed
to imatinib and sunitinib
Secondary endpoints:
- To determinate the objective response rate (ORR, complete response + partial response)
- To determinate the time to tumor progression (TTP)
- To evaluate the safety and toxicity profiles of AUY922
- To evaluate the pharmacokinetics profile of AUY922 in Taiwan GIST population
- To access the pharmacodynamic effect of AUY922 on HSP client proteins in blood and tumor
if feasible , i.e. HSP70, in Taiwan GIST population
- To access the tissue biomarkers pre-treatment and 4wks post treatment if feasible, i.e.
HSP70, c-KIT, PDGFRA mutation, ...etc in Taiwan GIST population
Exploratory endpoints:
•PET imaging; sSUVmax
Detailed Description
This is an open-label; pharmacokinetic and pharmacodynamic phase II study of AUY922 in
patients with advanced GIST failed to or intolerance of imatinib and sunitinib therapy.
AUY922 is a novel HSP90 inhibitor and will be administered at dose of 70 mg/m2 i.v. infusion
on D1 every week. The Simon one sample two-stage minimax design was used with 15 suitable
patients to be accrued to the first stage. If at least two patients meet our primary endpoint
(complete response+partial response+stable disease≧4 months), an additional 10 patients would
be recruited to the second stage. AUY922 would be considered active in this patient
population, if there were more than 5 cases of non-progressive disease in the total cohort of
25 patients.
Trial Arms
Name | Type | Description | Interventions |
---|
AUY922 | Experimental | AUY922 | |
Eligibility Criteria
Inclusion Criteria:
1. Patients with histologically proven CD117-positive and/or c-kit or PDGFR mutation
gastrointestinal stromal tumor (GIST), which is metastatic or unresectable, locally
advanced, and have failed to or intolerance of prior imatinib and sunitinib treatment
2. At least one measurable lesion according to the RECIST criteria (version 1.1)
3. Aged between 20-75 years
4. With Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
5. Life expectancy ≥ 4 months
6. At least 4 weeks apart from prior systemic (including chemotherapy, approved targeted
therapy or investigational agent) and surgical treatment, and recovery from all prior
treatment-related toxicity to grade < 1 according to Common Terminology Criteria for
Adverse Events (CTCAE) v4.0.
7. With adequate organ and marrow function as defined below:
- WBC ≥ 3.00 × 103/ mm3 and absolute neutrophil count ≥ 1.50 × 103/ mm3
- Platelet count ≥ 100.0 × 103/mm3
- Hemoglobin level ≥ 9 gm/dL
- Serum creatinine (Cr) ≦1.5 x UNL or eGFR ≥ 60 ml/min (by Cockroft-Gault method)
- Serum bilirubin ≤ 1.5 x UNL , ALT ≤ 2.5x UNL. If obstructive jaundice with proper
drainage, serum bilirubin ≤ 3 x UNL is acceptable.
8. Women of childbearing potential and men must agree to use accepted methods of
contraception during the course of the study and at least 3 months after last dose of
treatment
9. Willing to have tumor biopsy at screening (all patients) and able to comply with study
requirement at 4 weeks post treatment
10. With ability to understand and the willingness to sign Informed Consent Form.
Exclusion Criteria:
1. Have received imatinib or sunitinib, chemotherapy, any investigational agents or
participate in any investigational drug study within 28 days before enrolment
2. Have major surgery within 28 days before enrolment (diagnostic biopsy or line
placement is not considered major surgery)
3. With active multiple cancers or history of other malignancy within the last three
years, except treated curable non-melanoma skin cancer, in-situ cervical cancer,
Dukes' A colorectal cancer.
4. With known CNS metastasis
5. Symptoms of heart failure or greater to Class III (by NYHA criteria) or history of
uncontrolled dysrrhythmias
6. Sinus bradycardia (resting heart rate <50 beats/min) secondary to intrinsic conduction
system disease; Patients with sinus bradycardia secondary to pharmacologic treatment
may enrol if they are allowed to withdraw the treatment and can result in
normalization of the resting heart rate to within normal limits
7. Myocardial infarction or active ischemic heart within 6 months
8. Screening QTc >450 msec in males; QTc >470 msec in females, or previous history of QTc
prolongation while taking other medications
9. Presence of active infection or systemic use of antimicrobials within 72 hours prior
to enrolment
10. Treatment with therapeutic doses of coumadin-type anticoagulants. [Maximum daily dose
of 2mg, for line patency permitted]
11. Patients who are unable to comply protocol requirement, i.e. tumor tissue sampling or
blood sampling for pharmacodynamic and pharmacokinetics study
12. Patients who have know hypersensitivity or prior therapy of any HSP90 inhibitor
compound or its derivatives
Maximum Eligible Age: | 75 Years |
Minimum Eligible Age: | 20 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | disaese control rate |
Time Frame: | 4 months |
Safety Issue: | |
Description: | The primary endpoint of this study is to assess disease control rate (complete response + partial response + stable disease≧4 months) of AUY922 in patients with advanced GIST failed to imatinib and sunitinib |
Secondary Outcome Measures
Measure: | response rate |
Time Frame: | 3 years |
Safety Issue: | |
Description: | To determinate the objective response rate (ORR, complete response + partial response)
To determinate the time to tumor progression (TTP)
To evaluate the safety and toxicity profiles of AUY922
To evaluate the pharmacokinetics profile of AUY922 in Taiwan GIST population
To access the pharmacodynamic effect of AUY922 on HSP client proteins in blood and tumor if feasible , i.e. HSP70, in Taiwan GIST population
To access the tissue biomarkers pre-treatment and 4wks post treatment if feasible, i.e. HSP70, c-KIT, PDGFRA mutation, ...etc in Taiwan GIST population |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Unknown status |
Lead Sponsor: | National Health Research Institutes, Taiwan |
Trial Keywords
- GIST(Gastrointestinal stromal tumor)
- HSP(Heat Shock Protein)
- Biomarker
Last Updated
February 25, 2015