Rechallenge of Imatinib in GIST Having no Effective Treatment: RIGHT

Study Overview
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Brief Summary
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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.

Official Title
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A Prospective, Double Blind, Randomized, Placebo-Controlled Phase III Trial of Imatinib Re-Challenge in Patients With Gastrointestinal Stromal Tumor Who Had Benefit From Prior Imatinib But Progression From Both Imatinib and Sunitinib

Conditions
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Gastrointestinal Stromal Tumors

Intervention / Treatment
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* Drug: Imatinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imatinib<br>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. | Drug: Imatinib<br>* 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.<br>* Other names: Glivec;|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | To compare the progression free survival (PFS) assessed by the blinded independent central review following resumption of dosing (re-challenge) with Imatinib plus best supportive care versus placebo plus best supportive care in patients with unresectable or metastatic GIST following failure of at least prior imatinib and sunitinib therapies | up tp12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate | Inclusion of complete response, partial response or stable disease Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; Progressive disease (PD), >20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD), Insufficient change to qualify for PR or PD. | up to 12 weeks | 
| Progression Free Survival | To compare PFS assessed by investigators | up to 12 weeks | 
| Response Rate | Tumour responses were initially determined by the local investigators in accordance with RECIST 1.0.Treatment decisions were based on local onsite radiological review. All imaging data were subsequently collected, anonymised, and reviewed centrally in a double-blind manner by two external academic radiology reviewers. Response assessment was determined in a masked central review by use of RECIST1.1. | Up to 12weeks | 
| Overall Survival(OS) and Time to Progression(TTP) | To compare the overall survival (OS) and time to progression (TTP) in both arms of the study | Up to 3years | 
| Safety and Tolerability of Imatinib | percentage of patients who experienced toxicity from study treatment to evaluate the safety and tolerability of imatinib re-challenge in this patient population | Up to 3years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Imatinib, Re-challenge