Clinical Trials /

A Study of AUY922 for GIST(Gastrointestinal Stromal Tumor) Patients

NCT01389583

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

Related Conditions:
  • Gastrointestinal Stromal Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
AUY922AUY922

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

NameTypeDescriptionInterventions
AUY922ExperimentalAUY922
  • 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:Recruiting
Lead Sponsor:National Health Research Institutes, Taiwan

Trial Keywords

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

Last Updated

February 23, 2015