A Phase 2 Study of XL820 in Adults With Advanced GIST Resistant to Imatinib and/or Sunitinib

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the clinical benefit of the KIT inhibitor XL820 in subjects with advanced gastrointestinal stromal tumors (GIST) who are resistant to or intolerant of Imatinib and/or Sunitinib.

Official Title
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A Phase 2 Study of XL820 in Subjects With Advanced Gastrointestinal Stromal Tumors Resistant to or Intolerant of Imatinib and/or Sunitinib

Conditions
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Gastrointestinal Stromal Tumors, Gastrointestinal Neoplasms

Intervention / Treatment
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* Drug: XL820
* Drug: XL820


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with metastatic or locally advanced or unresectable GIST who have intolerance of or disease progression following prior treatment with imatinib and/or sunitinib ECOG (Eastern Cooperative Oncology Group) performance status ≤2 Must have measurable disease per RECIST (Response Evaluation Criteria in Solid Tumors) Recovery from toxicity from prior therapy to Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤1 or to subject's baseline status Adequate organ and marrow function Sexually active subjects (male and female) must agree to use accepted methods of contraception during the course of the study and for 3 months following discontinuation of study drugs. Female subjects of childbearing potential must have a negative pregnancy test at enrollment. Exclusion Criteria: Therapy with imatinib or sunitinib within 14 days before the first dose of study drug Chemotherapy, immunotherapy, targeted therapy, chemoembolization, or any investigational drug for the treatment of GIST after the last dose of imatinib or sunitinib Anticoagulation with warfarin or coumarin-related compounds Radiation to ≥25% of bone marrow within 28 days of study entry Treatment with other investigational agents within 28 days of the first dose of XL820 Known central nervous systems metastases Uncontrolled or intercurrent illness Pregnancy or breast-feeding Active bacterial or viral infection requiring systemic treatment

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: XL820<br>* XL820 capsules administered orally as a single agent at a dose of 800 mg daily<br>|
| Experimental: B<br> | Drug: XL820<br>* XL820 capsules administered orally as a single agent at a dose of 300 mg twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit, defined as either confirmed complete response, confirmed partial response, or evidence of stable disease lasting ≥16 weeks, in subjects with advanced GIST resistant to/intolerant of imatinib and/or sunitinib |  | Assessed at baseline, Week 4 and 8, and every 8 weeks thereafter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of XL820 |  | Assessed at each visit | 
| Progression-free survival, duration of response, and overall survival |  | Assessed until progression | 
| Further characterize the pharmacokinetic and pharmacodynamic parameters of XL820 in subjects with advanced GIST |  | Assessed during periodic visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GIST, Gastrointestinal Cancer