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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 : Unknown
Verified January 2018 by Min-Hee Ryu, Asan Medical Center.
Recruitment status was:  Recruiting
First Posted : March 18, 2016
Last Update Posted : January 11, 2018
Sponsor:
Information provided by (Responsible Party):
Min-Hee Ryu, Asan Medical Center

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.

Condition or disease Intervention/treatment Phase
Gastrointestinal Stromal Tumors (GISTs) Drug: Imatinib Mesylate Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : January 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: Intermittent dosing arm
one-week on and one-week off schedule(Imatinib Mesylate, 400 mg once daily, oral)
Drug: Imatinib Mesylate
Sham Comparator: Continuous dosing arm
continuous dosing without off-treatment schedule(Imatinib Mesylate, 400 mg once daily, oral)
Drug: Imatinib Mesylate



Primary Outcome Measures :
  1. Progression-free survival by the modified RECIST criteria [ Time Frame: Up to 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02712112


Contacts
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Contact: Min-Hee Ryu, MD, PhD 82-2-3010-5935 miniryu@amc.seoul.kr

Locations
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Korea, Republic of
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Min-Hee Ryu, MD., Ph.D.    +82-10-5285-9492    miniryu@amc.seoul.kr   
Principal Investigator: Min-Hee Ryu, M.D., Ph.D.         
Sponsors and Collaborators
Asan Medical Center
Investigators
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Principal Investigator: Min-Hee Ryu, MD, PhD Asan Medical Center

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Responsible Party: Min-Hee Ryu, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT02712112    
Other Study ID Numbers: AMC1601
First Posted: March 18, 2016    Key Record Dates
Last Update Posted: January 11, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action