The Efficacy and Safety of Temozolomide in SDH-deficient GIST

Sponsor

Asan Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05661643

Collaborator

(none)

Enrollment

Location

Arm

58.9

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this clinical trial is to investigate the efficacy and safety of temozolomide in SDH deficiency GIST patients.

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Stromal Tumors	Drug: Temozolomide capsule	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

29 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Study to Evaluate the Efficacy and Safety of Temozolomide in Advanced Gastrointestinal Stromal Tumor Patients With SDH Deficiency

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Dec 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: temozolomide treatment	Drug: Temozolomide capsule 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)

Arm

Intervention/Treatment

Experimental: temozolomide treatment

Drug: Temozolomide capsule

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)

Outcome Measures

Primary Outcome Measures

Objective respone rate in SDH deficiency wild type GIST [up to 4 years]
complet response+partial response defined by RECIST v1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Asan Medical Center, University of Ulsan College of Medicine	Seoul		Korea, Republic of	138-736

Sponsors and Collaborators

Asan Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Yoon-Koo Kang, Professor, Asan Medical Center

ClinicalTrials.gov Identifier:

NCT05661643

Other Study ID Numbers:

AMC2203

First Posted:

Dec 22, 2022

Last Update Posted:

Dec 22, 2022

Last Verified:

Dec 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors

Temozolomide

Study Results

No Results Posted as of Dec 22, 2022