- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01541709
Imatinib Dose Escalation to 800 mg/Day in Korean Patients With Metastatic or Unresectable GIST Harboring KIT Exon 9 Mutation: KENEDI
December 27, 2023 updated by: Min-Hee Ryu, Asan Medical Center
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
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
23
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Seoul, Korea, Republic of, 138-736
- Asan Medical Center, University of Ulsan College of Medicine
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Imatinib
|
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)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
progression-free survival (PFS)
Time Frame: up to 24months
|
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
|
up to 24months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
disease control rate
Time Frame: Up to 24weeks
|
Up to 24weeks
|
safety control rate
Time Frame: up to 24months
|
up to 24months
|
overall survival (OS)
Time Frame: up to 24months
|
up to 24months
|
imatinib PK(pharmacokinetics) (Cmin)
Time Frame: up to 24months
|
up to 24months
|
percentage of successful dose escalation
Time Frame: up to 24months
|
up to 24months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Min-Hee Ryu, MD, PhD, Asan Medical Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 1, 2012
Primary Completion (Estimated)
December 31, 2024
Study Completion (Estimated)
December 31, 2024
Study Registration Dates
First Submitted
February 24, 2012
First Submitted That Met QC Criteria
February 24, 2012
First Posted (Estimated)
March 1, 2012
Study Record Updates
Last Update Posted (Estimated)
January 1, 2024
Last Update Submitted That Met QC Criteria
December 27, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Neoplasms, Connective Tissue
- Gastrointestinal Stromal Tumors
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Imatinib Mesylate
Other Study ID Numbers
- AMC1102
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Gastrointestinal Stromal Tumors
-
Washington University School of MedicineNorthwestern UniversityCompletedGastrointestinal Stromal Cell Tumors | Foregut Subepithelial LesionsUnited States
-
Centre Leon BerardGustave Roussy, Cancer Campus, Grand ParisCompletedSarcoma | Gastro-intestinal Stromal Tumors (GIST)France
-
AB ScienceCompletedGastro Intestinal Stromal TumorFrance
-
Centre Leon BerardRecruiting
-
Institut BergoniéFrench Sarcoma GroupRecruitingGastro Intestinal Stromal TumorFrance
-
University Medical Center GroningenDutch Cancer SocietyRecruitingGastro-intestinal Stromal TumorNetherlands
-
AB ScienceCompletedGastro-intestinal Stromal TumoursFrance
-
National University Hospital, SingaporeUnknownAsian Patients With Advanced Gastro-intestinal Stromal Tumors (GIST) Treated With ImatinibSingapore
-
Blueprint Medicines CorporationCompletedGastrointestinal Stromal Tumors (GIST) | Other Relapsed or Refractory Solid TumorsUnited States, United Kingdom, France, Korea, Republic of, Belgium, Germany, Italy, Netherlands, Poland, Spain
-
Institut BergoniéCompletedAdvanced Gastrointestinal Stromal TumorsFrance
Clinical Trials on imatinib
-
Centre Leon BerardCompletedGastrointestinal Stromal Tumors | Resected Gastrointestinal Stromal Tumors | Non-metastatic | High Risk of Recurrence | KIT Gene MutationFrance
-
Scandinavian Sarcoma GroupCompleted
-
Sarit AssoulineNovartisRecruitingChronic Myeloid Leukemia | Chronic Myeloid Leukemia in Remission | Chronic Myeloid Leukemia, BCR/ABL-PositiveCanada
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.CompletedChronic Myeloid LeukemiaChina
-
Seoul St. Mary's HospitalNovartisUnknownChronic Myeloid LeukemiaKorea, Republic of
-
M.D. Anderson Cancer CenterNovartisCompletedGastrointestinal Stromal TumorsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedMelanoma | Skin NeoplasmsUnited States
-
Novartis PharmaceuticalsCompletedGastrointestinal Stromal TumorsUnited States, France, Belgium, Germany
-
University of Auckland, New ZealandLeukaemia & Blood Cancer New ZealandActive, not recruiting
-
Novartis PharmaceuticalsCompletedPulmonary Arterial HypertensionAustria, Germany, United States, United Kingdom