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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by National Health Research Institutes, Taiwan
Sponsor:
Collaborators:
National Taiwan University Hospital
Taipei Veterans General Hospital, Taiwan
Mackay Memorial Hospital
Taichung Veterans General Hospital
China Medical University Hospital
National Cheng-Kung University Hospital
Chang Gung Memorial Hospital
Information provided by (Responsible Party):
National Health Research Institutes, Taiwan
ClinicalTrials.gov Identifier:
NCT01389583
First received: July 6, 2011
Last updated: September 14, 2013
Last verified: September 2013
  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


Condition Intervention Phase
Gastrointestinal Stromal Tumor
Drug: AUY922
Phase 2

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

Resource links provided by NLM:


Further study details as provided by National Health Research Institutes, Taiwan:

Primary Outcome Measures:
  • disaese control rate [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    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:
  • response rate [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    • 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


Estimated Enrollment: 25
Study Start Date: October 2011
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: AUY922
    70 mg/m2 60-min i.v. infusion weekly
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.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01389583

Contacts
Contact: Brong-rong Chen, BS 886-2-2653-4401 ext 25162 brong@nhri.org.tw

Locations
Taiwan
National Health Research of Institutes, Taiwan Cooperative Oncology Group Recruiting
Tainan, Taiwan
Principal Investigator: Kun-Huei Yeh, PhD         
Principal Investigator: Chueh-Chuan Yen, PhD         
Principal Investigator: Ken-Hong Lim, MD         
Principal Investigator: Jen-Shi Chen         
Principal Investigator: Cheng-Chung Wu, MS         
Principal Investigator: Chang-Fang Chiu, PhD         
Principal Investigator: Kuan-Der Lee, PhD         
Principal Investigator: Kun-Ming Rau, MPH         
Sub-Investigator: Ann-Lii Cheng, PhD         
Sub-Investigator: Yu-Lin Lin, MD         
Sub-Investigator: Ta-Chung Chao, MD         
Sub-Investigator: Wen-Liang Fang, MD         
Sub-Investigator: Ruey-Kuen Hsieh, MD         
Sub-Investigator: Chun-Nan Yeh, MD         
Sub-Investigator: Youngsen Yang, MD         
Sub-Investigator: Tseng-Hsi Lin, PhD         
Sub-Investigator: Mei-Due Yang, PhD         
Sub-Investigator: Li-Yuan Bai, MD         
Sub-Investigator: Wu-Chou Su, MD         
Sub-Investigator: Yan-Shen Shan, PhD         
Sub-Investigator: Nai-Jung Chiang, MD         
Sub-Investigator: Yen-Yang Chen, MD         
Sponsors and Collaborators
National Health Research Institutes, Taiwan
National Taiwan University Hospital
Taipei Veterans General Hospital, Taiwan
Mackay Memorial Hospital
Taichung Veterans General Hospital
China Medical University Hospital
National Cheng-Kung University Hospital
Chang Gung Memorial Hospital
Investigators
Principal Investigator: Li-Tzong Chen, M.D. ,Ph.D National Health Research of Institutes, Taiwan Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Health Research Institutes, Taiwan
ClinicalTrials.gov Identifier: NCT01389583     History of Changes
Other Study ID Numbers: T2211
Study First Received: July 6, 2011
Last Updated: September 14, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by National Health Research Institutes, Taiwan:
GIST(Gastrointestinal stromal tumor)
HSP(Heat Shock Protein)
Biomarker

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue

ClinicalTrials.gov processed this record on November 27, 2014