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The Efficacy and Safety of Temozolomide in SDH-deficient GIST (GIST)

Primary Purpose

Gastrointestinal Stromal Tumors

Status
Not yet recruiting
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Temozolomide capsule
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastrointestinal Stromal Tumors

Eligibility Criteria

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

Inclusion Criteria: Age 20 years or older, at the time of acquisition of informed consent Histologically confirmed GIST with CD117(+), DOG-1(+) Wild type GIST without KIT or PDGFRα gene mutations determined by Sanger sequencing and panel sequencing Eastern Cooperative Oncology Group (ECOG) performance status 0 ~ 2 Resolution of all adverse events with prior treatments to grade 0 or 1 by NCI-CTCAE version 5.0 At least one measurable lesion by RECIST version 1.1. Adequate bone marrow, hepatic, renal, and other organ functions, before adjuvant imatinib treatment Neutrophil >1,500/mm3 Platelet > 100,000/mm3 Hemoglobin >8.0 g/dL Total bilirubin < 1.5 x upper limit of normal (ULN) AST/ALT < 2.5 x ULN Creatinine <1.5 x ULN Life expectancy ≥12 weeks Disease progression or discontinuation of treatment due to intolerable toxicity at least with palliative 1st line imatinib . Washout period of previous TKIs or chemotherapy for more than 4 times the half life ((Imitinib and regorafenib need 1 week and sunitinib need 2 weeks.) Provision of a signed written informed consent Exclusion Criteria: Confirmed GIST with KIT or PDGFRα gene mutations determined by Sanger sequencing and panel sequencing Women of child-bearing potential who are pregnant or breast feeding Women or men who are not willing to use effective contraception entering the study period or until at least 6 months after the last study drug administration If any of the following applies within ≤ 6 months prior to starting study enrollment : Myocardial Infarction, severe instable angina, coronary/peripheral bypass, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack, treatment required severe arrhythmia Uncontrolled infection Acute and chronic liver disease and all chronic liver impairment.(But Patients with stable chronic hepatitis B are eligible Acute, or chronic medical or psychiatric condition or laboratory abnormality such as active uncontrolled infection that difficult to study participation in the judgment of the investigator Known diagnosis of HIV infection (HIV testing is not mandatory). History of another primary malignancy that is currently clinically significant or currently requires active intervention. Alcohol or substance abuse disorder The patients with NTRK fusion 5)

Sites / Locations

  • Asan Medical Center, University of Ulsan College of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

temozolomide treatment

Arm Description

Outcomes

Primary Outcome Measures

Objective respone rate in SDH deficiency wild type GIST
complet response+partial response defined by RECIST v1.1

Secondary Outcome Measures

Full Information

First Posted
December 14, 2022
Last Updated
June 11, 2023
Sponsor
Asan Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05661643
Brief Title
The Efficacy and Safety of Temozolomide in SDH-deficient GIST
Acronym
GIST
Official Title
A Phase 2 Study to Evaluate the Efficacy and Safety of Temozolomide in Advanced Gastrointestinal Stromal Tumor Patients With SDH Deficiency
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 30, 2023 (Anticipated)
Primary Completion Date
December 1, 2026 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this clinical trial is to investigate the efficacy and safety of temozolomide in SDH deficiency GIST patients.
Detailed Description
Wild type GISTs are less responsive to imatinib with a response rate of 23.1-44.6% and a median progressiion-free survival of 12.3-12.8 months. The efficacy of imatinib is limited in particular in SDH deficienctGIST with a reported response of 2%. Therefore, the development of a new therapeutic agents is urgently needed. Recently, a study of TKI-resistant SDH-deficient preclinical model showed that temozolomide, an alkylating agent, promotes DNA damage in tumor cells, leading to tumor cell killing. In a retrospective analysis, 2 out of 5 SDH deficient GIST patients treated with temozolomide showed partial response, suggesting its efficacy in this patient population. Based on these findings,The goal of this clinical trial is to investigate the efficacy and safety of temozolomide in SDH deficiency GIST patients. In addition, for exploratory purposes, aim to investigate the efficacy and safety of temozolomide in KIT and PDGFRA wild-type GIST without SDH deficiency.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
temozolomide treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Temozolomide capsule
Intervention Description
Temozolomide 200 mg/m2 is administered orally for 1-5 days of each cycle, and then canceled for 23 days (a total of 28 days is 1 cycle)
Primary Outcome Measure Information:
Title
Objective respone rate in SDH deficiency wild type GIST
Description
complet response+partial response defined by RECIST v1.1
Time Frame
up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 20 years or older, at the time of acquisition of informed consent Histologically confirmed GIST with CD117(+), DOG-1(+) Wild type GIST without KIT or PDGFRα gene mutations determined by Sanger sequencing and panel sequencing Eastern Cooperative Oncology Group (ECOG) performance status 0 ~ 2 Resolution of all adverse events with prior treatments to grade 0 or 1 by NCI-CTCAE version 5.0 At least one measurable lesion by RECIST version 1.1. Adequate bone marrow, hepatic, renal, and other organ functions, before adjuvant imatinib treatment Neutrophil >1,500/mm3 Platelet > 100,000/mm3 Hemoglobin >8.0 g/dL Total bilirubin < 1.5 x upper limit of normal (ULN) AST/ALT < 2.5 x ULN Creatinine <1.5 x ULN Life expectancy ≥12 weeks Disease progression or discontinuation of treatment due to intolerable toxicity at least with palliative 1st line imatinib . Washout period of previous TKIs or chemotherapy for more than 4 times the half life ((Imitinib and regorafenib need 1 week and sunitinib need 2 weeks.) Provision of a signed written informed consent Exclusion Criteria: Confirmed GIST with KIT or PDGFRα gene mutations determined by Sanger sequencing and panel sequencing Women of child-bearing potential who are pregnant or breast feeding Women or men who are not willing to use effective contraception entering the study period or until at least 6 months after the last study drug administration If any of the following applies within ≤ 6 months prior to starting study enrollment : Myocardial Infarction, severe instable angina, coronary/peripheral bypass, NYHA class III or IV congestive heart failure, stroke or transient ischemic attack, treatment required severe arrhythmia Uncontrolled infection Acute and chronic liver disease and all chronic liver impairment.(But Patients with stable chronic hepatitis B are eligible Acute, or chronic medical or psychiatric condition or laboratory abnormality such as active uncontrolled infection that difficult to study participation in the judgment of the investigator Known diagnosis of HIV infection (HIV testing is not mandatory). History of another primary malignancy that is currently clinically significant or currently requires active intervention. Alcohol or substance abuse disorder The patients with NTRK fusion 5)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kim Hyung-Don, MD, PhD
Phone
82-2-10-3694-6110
Email
kimhdmd@amc.seoul.kr
First Name & Middle Initial & Last Name or Official Title & Degree
Ruy Min-Hee, MD, PhD
Phone
82-2-3010-5936
Email
miniryu@amc.seoul.kr
Facility Information:
Facility Name
Asan Medical Center, University of Ulsan College of Medicine
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

The Efficacy and Safety of Temozolomide in SDH-deficient GIST

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