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A Study of Intermittent Dosing Schedule of Imatinib in Patients With Tyrosine Kinase Inhibitor Refractory GISTs

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ClinicalTrials.gov Identifier: NCT02712112
Recruitment Status : Recruiting
First Posted : March 18, 2016
Last Update Posted : October 20, 2021
Sponsor:
Information provided by (Responsible Party):
Min-Hee Ryu, Asan Medical Center

Tracking Information
First Submitted Date  ICMJE March 9, 2016
First Posted Date  ICMJE March 18, 2016
Last Update Posted Date October 20, 2021
Actual Study Start Date  ICMJE January 2016
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 12, 2021)
disease control rate [ Time Frame: at 12 weeks ]
disease control rate at 12 weeks
Original Primary Outcome Measures  ICMJE
 (submitted: March 14, 2016)
Progression-free survival by the modified RECIST criteria [ Time Frame: Up to 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Intermittent Dosing Schedule of Imatinib in Patients With Tyrosine Kinase Inhibitor Refractory GISTs
Official Title  ICMJE Randomized Phase 2 Study of Intermittent vs Continuous Dosing Schedule of Imatinib in Patients With Tyrosine Kinase Inhibitor Refractory Gastrointestinal Stromal Tumors (GISTs)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Gastrointestinal Stromal Tumors (GISTs)
Intervention  ICMJE Drug: Imatinib Mesylate
Study Arms  ICMJE
  • Experimental: Intermittent dosing arm
    one-week on and one-week off schedule(Imatinib Mesylate, 400 mg once daily, oral)
    Intervention: Drug: Imatinib Mesylate
  • Sham Comparator: Continuous dosing arm
    continuous dosing without off-treatment schedule(Imatinib Mesylate, 400 mg once daily, oral)
    Intervention: Drug: Imatinib Mesylate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 14, 2016)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Min-Hee Ryu, MD, PhD 82-2-3010-5935 miniryu@amc.seoul.kr
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02712112
Other Study ID Numbers  ICMJE AMC1601
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Min-Hee Ryu, Asan Medical Center
Study Sponsor  ICMJE Asan Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Min-Hee Ryu, MD, PhD Asan Medical Center
PRS Account Asan Medical Center
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP