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Imatinib Dose Escalation to 800 mg/Day in Korean Patients With Metastatic or Unresectable GIST Harboring KIT Exon 9 Mutation: KENEDI

Primary Purpose

Gastrointestinal Stromal Tumors

Status

Active

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

imatinib

About this trial

This is an interventional treatment trial for Gastrointestinal Stromal Tumors focused on measuring This is a single-center, prospective, single-arm, open-label phase II study

Eligibility Criteria

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

Inclusion Criteria:

Age 18 or older
Histologically confirmed metastatic or unresectable GIST with CD117(+), DOG-1 (+), or KIT mutation
ECOG PS(Eastern Cooperative Oncology Group Performance Status) 0~2
Primary mutation at KIT exon 9
Imatinib treatment for less than 4 weeks from the first dose at 400 mg per day
No prior use of tyrosine kinase inhibitors ((but, patients who have recurrence 6 months after completion of adjuvant imatinib at a dose of 400 mg per day can be enrolled in this study)
At least one evaluable disease by RECIST v1.0
Resolution of all toxic effects of prior treatments (chemotherapy, surgery, RFA(radiofrequency ablation), radiotherapy, and/or TACE)
Adequate bone marrow function as defined by platelets ≥ 75 x 109/L and neutrophils ≥ 1.5 x 109/L (within 1 week prior to the first dose of imatinib at 400 mg per day)
Adequate renal function, with serum creatinine < 1.5 x ULN (within 1 week prior to the first dose of imatinib at 400 mg per day)
Adequate hepatic function with serum total bilirubin < 1.5 x ULN, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN in the absence of liver metastases, or < 5 x UNL in the presence of liver metastases (within 1 week prior to the first dose of imatinib at 400 mg per day)
No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer except where treated with curative intent > 5 years previously without evidence of relapse
Provision of a signed written informed consent

Exclusion Criteria:

Severe co-morbid illness and/or active infections
Pregnant or lactating women
History of other malignancies except basal cell carcinoma and carcinoma in situ of uterine cervix
CNS metastasis
Clinically significant bleeding in GI tract
GI obstruction or malabsorption
Known hypersensitivity to imatinib

Sites / Locations

Asan Medical Center, University of Ulsan College of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Imatinib

Arm Description

Outcomes

Primary Outcome Measures

progression-free survival (PFS)

evaluated with Triphasic or dynamic CT scans of abdomen & pelvis, and other involved sites. Follow-up CT scans will be performed at 4 weeks and 12 weeks after the first dose of imatinib at 400 mg per day, and then every 3 months until disease using RECIST(Response Evaluation Criteria in Solid Tumors) version 1.0

Secondary Outcome Measures

disease control rate

safety control rate

overall survival (OS)

imatinib PK(pharmacokinetics) (Cmin)

percentage of successful dose escalation

Full Information

NCT ID

NCT01541709

First Posted

February 24, 2012

Last Updated

December 30, 2022

Sponsor

Asan Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01541709

Brief Title

Imatinib Dose Escalation to 800 mg/Day in Korean Patients With Metastatic or Unresectable GIST Harboring KIT Exon 9 Mutation: KENEDI

Official Title

A Phase II Study of Imatinib Dose Escalation to 800 mg/Day in Korean Patients With Metastatic or Unresectable GIST Harboring KIT Exon 9 Mutation: Imatinib Dose Escalation

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 2012 (Actual)

Primary Completion Date

December 30, 2022 (Anticipated)

Study Completion Date

December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Asan Medical Center

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

KIT exon 9 mutants had poorer survival compared with KIT exon 11 mutants when they were treated with the same dose of imatinib, 400 mg per day, and that patients with KIT exon 9 mutation had better progression-free survival with imatinib treatment at an escalated dose, 800 mg per day, than with imatinib treatment at a dose of 400 mg per day.10,11 Based on the results, imatinib 800 mg per day is now considered the standard dose for the treatment of patients with metastatic or unresectable GIST showing KIT exon 9 mutation in Western countries.

Detailed Description

According to our previous prospective phase II study of imatinib 400 mg per day in metastatic or unresectable GIST, hematologic and non-hematologic toxicities were more frequent in Korean patients compared to the Western studies.7 It may be caused by relatively higher exposure to imatinib per body surface area in Korean patients than in Western population because the weight and height of Korean patients are relatively smaller than Western people. So, we plan to start imatinib at 400 mg per day and then sequentially escalate the doses of imatinib in this study.

6. Conditions and Keywords

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

Gastrointestinal Stromal Tumors

Keywords

This is a single-center, prospective, single-arm, open-label phase II study

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Imatinib

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

imatinib

Intervention Description

The patients will receive 400 mg per day of imatinib for 4 weeks, and then 600mg per day (300 mg po bid) for 4 weeks if tolerable to 400 mg per day, and then 800 mg per day (400 mg po bid)

Primary Outcome Measure Information:

Title

progression-free survival (PFS)

Description

Time Frame

up to 24months

Secondary Outcome Measure Information:

Title

disease control rate

Time Frame

Up to 24weeks

Title

safety control rate

Time Frame

up to 24months

Title

overall survival (OS)

Time Frame

up to 24months

Title

imatinib PK(pharmacokinetics) (Cmin)

Time Frame

up to 24months

Title

percentage of successful dose escalation

Time Frame

up to 24months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18 or older Histologically confirmed metastatic or unresectable GIST with CD117(+), DOG-1 (+), or KIT mutation ECOG PS(Eastern Cooperative Oncology Group Performance Status) 0~2 Primary mutation at KIT exon 9 Imatinib treatment for less than 4 weeks from the first dose at 400 mg per day No prior use of tyrosine kinase inhibitors ((but, patients who have recurrence 6 months after completion of adjuvant imatinib at a dose of 400 mg per day can be enrolled in this study) At least one evaluable disease by RECIST v1.0 Resolution of all toxic effects of prior treatments (chemotherapy, surgery, RFA(radiofrequency ablation), radiotherapy, and/or TACE) Adequate bone marrow function as defined by platelets ≥ 75 x 109/L and neutrophils ≥ 1.5 x 109/L (within 1 week prior to the first dose of imatinib at 400 mg per day) Adequate renal function, with serum creatinine < 1.5 x ULN (within 1 week prior to the first dose of imatinib at 400 mg per day) Adequate hepatic function with serum total bilirubin < 1.5 x ULN, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN in the absence of liver metastases, or < 5 x UNL in the presence of liver metastases (within 1 week prior to the first dose of imatinib at 400 mg per day) No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer except where treated with curative intent > 5 years previously without evidence of relapse Provision of a signed written informed consent Exclusion Criteria: Severe co-morbid illness and/or active infections Pregnant or lactating women History of other malignancies except basal cell carcinoma and carcinoma in situ of uterine cervix CNS metastasis Clinically significant bleeding in GI tract GI obstruction or malabsorption Known hypersensitivity to imatinib

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yoon-Koo Kang, MD, PhD

Organizational Affiliation

Asan Medical Center

Official's Role

Principal Investigator

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

Imatinib Dose Escalation to 800 mg/Day in Korean Patients With Metastatic or Unresectable GIST Harboring KIT Exon 9 Mutation: KENEDI

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