Imatinib TDM in GIST

Study Overview
=================
Brief Summary
-----------------
Imatinib can lead to long recurrence free survival in patients diagnosed with gastrointestinal stromal tumors (GIST); however side effects can significantly hinder quality of life for our patients. This study will use therapeutic drug monitoring to improve quality of life and symptoms and assess how many patients maintain therapeutic levels. Free drug levels and pharmokinetics of imatinib will also be monitored.

Official Title
-----------------
A Phase 2 Study of Imatinib Therapeutic Drug Monitoring in Gastrointestinal Stromal Tumor

Conditions
-----------------
Gastrointestinal Stromal Tumors

Intervention / Treatment
-----------------
* Drug: Imatinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed GIST with KIT mutation or PDGFRA mutation (non-D842V) Currently receiving imatinib initiated within the last 3 months or to be started in the next 1 month Prior systemic chemotherapy for other malignancy is allowed as long as it was completed within the past 6 months and there is no evidence of disease Age ≥18 years ECOG performance status of 0 or 1 Normal organ function Exclusion Criteria: Presence of PDGFRA D842V mutation Known allergy to imatinib or allergic reactions to compounds of similar chemical or biologic composition to the study drug Concomitant anticoagulation with oral warfarin. Use of strong inhibitors or inducers of CYP3A or CYP3A4, drugs metabolized by CYP3A4 or CYP2D6 Uncontrolled intercurrent illness Concurrent malignancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imatinib TDM<br>Patients with diagnosed gastrointestinal stromal tumor (GIST) who are currently being treated with imatinib. | Drug: Imatinib<br>* Therapeutic drug level monitoring with plans to increase to adjust drug dosage based on levels and patient symptoms.<br>* Other names: Gleevec;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Grade 3/4 adverse events attributable to imatinib per CTCAE v5.0 | To compare the incidence of Grade 3/4 adverse events attributable to imatinib per CTCAE v5.0 in patients who receive therapeutic drug monitoring (TDM) with imatinib to a historical control. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of patients achieving therapeutic levels of imatinib. | Percent of patients achieving therapeutic levels of imatinib. | 6 months | 
| Quality of Life based on the EORTC QLQ-C30 | Quality of Life will be assessed using the EORTC Core Quality of Life questionnaire (EORTC QLQ-C30). The EORTC QLQ-C30 is designed to measure cancer patients' physical, psychological and social functions. It incorporates five functional scales, three symptom scales, a global health status, financial impact, and single items assessing additional symptoms. All scales and single-item measures are transformed so that scores range from 0-100; higher scores represent a higher response level. | 6 months | 
| Average dose of imatinib required to achieve therapeutic levels and drug dose over 3 years |  | 3 year |