Back to results

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

Primary Purpose

Gastrointestinal Stromal Tumor

Status

Unknown status

Phase

Phase 2

Locations

Taiwan

Study Type

Interventional

Intervention

AUY922

About this trial

This is an interventional treatment trial for Gastrointestinal Stromal Tumor focused on measuring GIST(Gastrointestinal stromal tumor), HSP(Heat Shock Protein), Biomarker

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
At least one measurable lesion according to the RECIST criteria (version 1.1)
Aged between 20-75 years
With Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
Life expectancy ≥ 4 months
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.
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.
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
Willing to have tumor biopsy at screening (all patients) and able to comply with study requirement at 4 weeks post treatment
With ability to understand and the willingness to sign Informed Consent Form.

Exclusion Criteria:

Have received imatinib or sunitinib, chemotherapy, any investigational agents or participate in any investigational drug study within 28 days before enrolment
Have major surgery within 28 days before enrolment (diagnostic biopsy or line placement is not considered major surgery)
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.
With known CNS metastasis
Symptoms of heart failure or greater to Class III (by NYHA criteria) or history of uncontrolled dysrrhythmias
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
Myocardial infarction or active ischemic heart within 6 months
Screening QTc >450 msec in males; QTc >470 msec in females, or previous history of QTc prolongation while taking other medications
Presence of active infection or systemic use of antimicrobials within 72 hours prior to enrolment
Treatment with therapeutic doses of coumadin-type anticoagulants. [Maximum daily dose of 2mg, for line patency permitted]
Patients who are unable to comply protocol requirement, i.e. tumor tissue sampling or blood sampling for pharmacodynamic and pharmacokinetics study
Patients who have know hypersensitivity or prior therapy of any HSP90 inhibitor compound or its derivatives

Sites / Locations

National Health Research of Institutes, Taiwan Cooperative Oncology GroupRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AUY922

Arm Description

AUY922

Outcomes

Primary Outcome Measures

disaese control rate

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

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

Full Information

NCT ID

NCT01389583

First Posted

July 6, 2011

Last Updated

February 23, 2015

Sponsor

National Health Research Institutes, Taiwan

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

1. Study Identification

Unique Protocol Identification Number

NCT01389583

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2013

Overall Recruitment Status

Unknown status

Study Start Date

October 2011 (undefined)

Primary Completion Date

May 2015 (Anticipated)

Study Completion Date

October 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Health Research Institutes, Taiwan

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastrointestinal Stromal Tumor

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

AUY922

Arm Type

Experimental

Arm Description

AUY922

Intervention Type

Drug

Intervention Name(s)

AUY922

Intervention Description

70 mg/m2 60-min i.v. infusion weekly

Primary Outcome Measure Information:

Title

disaese control rate

Description

Time Frame

4 months

Secondary Outcome Measure Information:

Title

response rate

Description

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 At least one measurable lesion according to the RECIST criteria (version 1.1) Aged between 20-75 years With Eastern Cooperative Oncology Group (ECOG) performance score 0-2. Life expectancy ≥ 4 months 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. 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. 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 Willing to have tumor biopsy at screening (all patients) and able to comply with study requirement at 4 weeks post treatment With ability to understand and the willingness to sign Informed Consent Form. Exclusion Criteria: Have received imatinib or sunitinib, chemotherapy, any investigational agents or participate in any investigational drug study within 28 days before enrolment Have major surgery within 28 days before enrolment (diagnostic biopsy or line placement is not considered major surgery) 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. With known CNS metastasis Symptoms of heart failure or greater to Class III (by NYHA criteria) or history of uncontrolled dysrrhythmias 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 Myocardial infarction or active ischemic heart within 6 months Screening QTc >450 msec in males; QTc >470 msec in females, or previous history of QTc prolongation while taking other medications Presence of active infection or systemic use of antimicrobials within 72 hours prior to enrolment Treatment with therapeutic doses of coumadin-type anticoagulants. [Maximum daily dose of 2mg, for line patency permitted] Patients who are unable to comply protocol requirement, i.e. tumor tissue sampling or blood sampling for pharmacodynamic and pharmacokinetics study Patients who have know hypersensitivity or prior therapy of any HSP90 inhibitor compound or its derivatives

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Brong-rong Chen, BS

Phone

886-2-2653-4401

Ext

25162

brong@nhri.org.tw

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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

Organizational Affiliation

National Health Research of Institutes, Taiwan Cooperative Oncology Group

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Health Research of Institutes, Taiwan Cooperative Oncology Group

City

Tainan

Country

Taiwan

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kun-Huei Yeh, PhD

First Name & Middle Initial & Last Name & Degree

Chueh-Chuan Yen, PhD

First Name & Middle Initial & Last Name & Degree

Ken-Hong Lim, MD

First Name & Middle Initial & Last Name & Degree

Jen-Shi Chen

First Name & Middle Initial & Last Name & Degree

Cheng-Chung Wu, MS

First Name & Middle Initial & Last Name & Degree

Chang-Fang Chiu, PhD

First Name & Middle Initial & Last Name & Degree

Kuan-Der Lee, PhD

First Name & Middle Initial & Last Name & Degree

Kun-Ming Rau, MPH

First Name & Middle Initial & Last Name & Degree

Ann-Lii Cheng, PhD

First Name & Middle Initial & Last Name & Degree

Yu-Lin Lin, MD

First Name & Middle Initial & Last Name & Degree

Ta-Chung Chao, MD

First Name & Middle Initial & Last Name & Degree

Wen-Liang Fang, MD

First Name & Middle Initial & Last Name & Degree

Ruey-Kuen Hsieh, MD

First Name & Middle Initial & Last Name & Degree

Chun-Nan Yeh, MD

First Name & Middle Initial & Last Name & Degree

Youngsen Yang, MD

First Name & Middle Initial & Last Name & Degree

Tseng-Hsi Lin, PhD

First Name & Middle Initial & Last Name & Degree

Mei-Due Yang, PhD

First Name & Middle Initial & Last Name & Degree

Li-Yuan Bai, MD

First Name & Middle Initial & Last Name & Degree

Wu-Chou Su, MD

First Name & Middle Initial & Last Name & Degree

Yan-Shen Shan, PhD

First Name & Middle Initial & Last Name & Degree

Nai-Jung Chiang, MD

First Name & Middle Initial & Last Name & Degree

Yen-Yang Chen, MD

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs