Back to resultsA Study of Intermittent Dosing Schedule of Imatinib in Patients With Tyrosine Kinase Inhibitor Refractory GISTs
Primary Purpose
Gastrointestinal Stromal Tumors (GISTs)
Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Imatinib Mesylate
Sponsored by
About this trial
This is an interventional treatment trial for Gastrointestinal Stromal Tumors (GISTs)
Eligibility Criteria
Inclusion Criteria:
- Patients aged 19 years and older
- Patients with metastatic or unresectable GIST which has been histologically confirmed by the detection of CD117 on immunohistochemical staining or genetically confirmed by the detection of mutation in KIT or PDGFRα genes on direct sequencing of tumor DNA.
- Prior clinical benefit from 1st line imatinib defined as CR, PR, or SD at 6 months after the start of 1st line imatinib
- Patients whose disease has progressed with at least both prior imatinib (400mg/day) and sunitinib therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 ~ 3
- Adequate bone marrow function as defined by platelets ≥ 75 x 109/L and neutrophils ≥ 1.5 x 109/L
- Adequate renal function, with serum creatinine < 1.5 x upper limit of normal (ULN)
- 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.
- Expected life expectancy of greater than 12 weeks in the absence of any intervention
- 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
- Written informed consent to the study
Exclusion Criteria:
- Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non-compliance
- Last dose of radiotherapy received within 4 weeks before the start of study treatment, excluding palliative radiotherapy
- Obstruction of gastrointestinal tract
- Active gastrointestinal bleeding
- Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)
- Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol
- Female patients who are pregnant or breast-feeding. Female patients must have had a negative pregnancy test within one week before starting imatinib.
Sites / Locations
- Asan Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Intermittent dosing arm
Continuous dosing arm
Arm Description
one-week on and one-week off schedule(Imatinib Mesylate, 400 mg once daily, oral)
continuous dosing without off-treatment schedule(Imatinib Mesylate, 400 mg once daily, oral)
Outcomes
Primary Outcome Measures
disease control rate
disease control rate at 12 weeks
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02712112
Brief Title
A Study of Intermittent Dosing Schedule of Imatinib in Patients With Tyrosine Kinase Inhibitor Refractory GISTs
Official Title
Randomized Phase 2 Study of Intermittent vs Continuous Dosing Schedule of Imatinib in Patients With Tyrosine Kinase Inhibitor Refractory Gastrointestinal Stromal Tumors (GISTs)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
March 16, 2016 (Actual)
Primary Completion Date
June 15, 2019 (Actual)
Study Completion Date
June 15, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Recent preclinical study has suggested a potential possibility that imatinib might promote tumor growth in the presence of secondary resistance mutations [10]. This result imply that intermittent dosing schedule of imatinib rechallenge might be better than continuous dosing schedule in terms of controlling tumors harboring secondary resistance mutations. In addition, in these heavily pretreated patients, even mild grade of toxicity may significantly impair quality of life, and intermittent dosing schedule may have an advantage in this context. Therefore, investigators hypothesize that intermittent dosing schedule of imatinib rechallenge might be feasible and effective in patients with TKI-refractory GISTs. This study will assess the feasibility of intermittent imatinib dosing schedule in patients with GISTs who had failures from both imatinib and sunitinib.
Detailed Description
Patients will be randomly assigned to an imatinib arm with either intermittent or continuous dosing schedule with a ratio of 1:1 by using a computer-based system. Imatinib will be administered at a dose of 400 mg/day, once a day with food, in the form of 100-mg tablets. Patients assigned to the continuous dosing arm will receive imatinib without off-schedule, and those assigned to the intermittent dosing arm will received imatinib with one-week on/one-week off dosing schedule. Four weeks of study treatment is considered as one cycle for both continuous and intermittent dosing schedules.
In both arms, the imatinib treatment beyond multiple progressions defined by RECIST version 1.1 is permitted, unless treating physician decided that there is no clinical benefit with imatinib. Imatinib will be discontinued when unacceptable toxicity or patient's withdrawal of consent.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Stromal Tumors (GISTs)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
51 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Intermittent dosing arm
Arm Type
Experimental
Arm Description
one-week on and one-week off schedule(Imatinib Mesylate, 400 mg once daily, oral)
Arm Title
Continuous dosing arm
Arm Type
Sham Comparator
Arm Description
continuous dosing without off-treatment schedule(Imatinib Mesylate, 400 mg once daily, oral)
Intervention Type
Drug
Intervention Name(s)
Imatinib Mesylate
Primary Outcome Measure Information:
Title
disease control rate
Description
disease control rate at 12 weeks
Time Frame
at 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients aged 19 years and older
Patients with metastatic or unresectable GIST which has been histologically confirmed by the detection of CD117 on immunohistochemical staining or genetically confirmed by the detection of mutation in KIT or PDGFRα genes on direct sequencing of tumor DNA.
Prior clinical benefit from 1st line imatinib defined as CR, PR, or SD at 6 months after the start of 1st line imatinib
Patients whose disease has progressed with at least both prior imatinib (400mg/day) and sunitinib therapy.
Eastern Cooperative Oncology Group (ECOG) performance status 0 ~ 3
Adequate bone marrow function as defined by platelets ≥ 75 x 109/L and neutrophils ≥ 1.5 x 109/L
Adequate renal function, with serum creatinine < 1.5 x upper limit of normal (ULN)
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.
Expected life expectancy of greater than 12 weeks in the absence of any intervention
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
Written informed consent to the study
Exclusion Criteria:
Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol or a history of non-compliance
Last dose of radiotherapy received within 4 weeks before the start of study treatment, excluding palliative radiotherapy
Obstruction of gastrointestinal tract
Active gastrointestinal bleeding
Myocardial infarction within 6 months prior to the study medication, and other clinically significant heart disease (e.g., unstable angina, congestive heart failure or uncontrolled hypertension)
Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol
Female patients who are pregnant or breast-feeding. Female patients must have had a negative pregnancy test within one week before starting imatinib.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Min-Hee Ryu, MD, PhD
Organizational Affiliation
Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
A Study of Intermittent Dosing Schedule of Imatinib in Patients With Tyrosine Kinase Inhibitor Refractory GISTs
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