Rechallenge of Imatinib in GIST Having no Effective Treatment: RIGHT
Condition: Gastrointestinal Stromal Tumors
MeSH terms: Gastrointestinal Stromal Tumors
Intervention: Imatinib; Placebo
Intervention description: Patients will be randomly assigned to receive imatinib at a dose of 400mg/day, taken once daily with food, in the form of 100-mg tablets. The study medication will be administered until disease progression, unacceptable toxicity, or withdrawal of consent.; Patients will be randomly assigned to receive placebo at a dose of 400mg/day, taken once daily with food, in the form of 100-mg tablets. The study medication will be administered until disease progression or withdrawal of consent.
Intervention MeSH terms: Imatinib Mesylate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Enrollment: 81.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Imatinib; Re-challenge

Summary:

      The objective of this study is to compare the clinical outcomes following resumption of
      dosing (re-challenge) with Imatinib plus best supportive care versus placebo plus best
      supportive care in patients with advanced/incurable Gastrointestinal Stromal Tumors following
      failure of prior imatinib and sunitinib therapies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients aged 18 years and older

          -  Patients with metastatic or unresectable malignant gastrointestinal stromal tumour
             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 benefit from 1st line imatinib defined as complete response, partial response,
             or stable disease at 6 months after the start of 1st line imatinib

          -  Patients whose disease has progressed despite at least both prior imatinib therapy
             (400mg/day) and then subsequently also failure of prior sunitinib therapy.

          -  ECOG(Eastern Cooperative Oncology Group) 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

          -  Adequate hepatic function with serum total bilirubin < 1.5 x upper limit of normal,
             alanine aminotransferase or aspartate aminotransferase < 2.5 x upper limit of normal
             in the absence of liver metastases, or < 5 x upper limit of normal 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.