Know Cancer

forgot password

A Phase II Study of AUY922, a Novel HSP Inhibitor, in Patients With Advanced GIST Failed to or Intolerance of Imatinib and Sunitinib Therapy

Phase 2
20 Years
75 Years
Not Enrolling
Gastrointestinal Stromal Tumor

Thank you

Trial Information

A Phase II Study of AUY922, a Novel HSP Inhibitor, in Patients With Advanced GIST Failed to or Intolerance of Imatinib and Sunitinib Therapy

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.

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

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

disaese control rate

Outcome 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

Outcome Time Frame:

4 months

Safety Issue:


Principal Investigator

Li-Tzong Chen, M.D. ,Ph.D

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Health Research of Institutes, Taiwan Cooperative Oncology Group


United States: Institutional Review Board

Study ID:




Start Date:

July 2011

Completion Date:

July 2019

Related Keywords:

  • Gastrointestinal Stromal Tumor
  • GIST(Gastrointestinal stromal tumor)
  • HSP(Heat Shock Protein)
  • Biomarker
  • Gastrointestinal Stromal Tumors