Pazopanib in Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib

Study Overview
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Brief Summary
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Patients with metastatic or locally advanced gastrointestinal stromal tumors (GIST) who develop resistance against the two hitherto approved drugs for this disease, the tyrosin kinase inhibitors (TKIs) imatinib and sunitinib, have a poor prognosis. Sometimes a further response may be achieved by other drugs, mainly other TKIs, which have been explored in different studies but not yet have been approved for clinical use. Pazopanib is a TKI inhibiting the tyrosin kinases KIT, PDGFRA, and VEGF 1-3, all of which have important roles in the pathogenesis of GIST. Theoretically, it may function in GIST, and it deserves investigational trials. The drug is approved for metastatic renal cancer and is relatively well tolerated. In this trial (SSG XXI), the disease control rate (DCR) = (CR+PR+SD) after 12 weeks of treatment will be assessed as the primary endpoint, and at the same time trough levels will be measured. Secondary endpoints include ORR, PFS, toxicity, and disease control rate in relation to trough level week 12 and in relation to the primary mutation of the tumor (if known). The goal is to include 72 patients in the trial, which is open and single arm.

Official Title
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Pazopanib in Advanced GISTs Refractory to Imatinib and Sunitinib - A Non-comparative Phase II Multicenter Study by the Scandinavian Sarcoma Group

Conditions
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Gastrointestinal Stromal Tumors

Intervention / Treatment
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* Drug: Pazopanib


Participation Criteria
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Eligibility Criteria
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Eligibility Criteria: Metastatic and/or locally advanced GIST, with diagnosis based on histology with positive c-kit and/or DOG-1, or with a GIST-typical mutation in KIT or PDGFR Measurable disease on CT (computed tomography) as defined by RECIST criteria; at least one measurable lesion not given radiotherapy History of progressive disease on CT according to RECIST criteria after both imatinib and sunitinib treatment, and also after nilotinib if this drug has been given No other TKIs given than imatinib, sunitinib and nilotinib Age at least 18 years at the time of diagnosis of GIST WHO performance status 0-2 Resolution of all toxic side effects from earlier TKI treatment and any other potential non-TKI treatment to grade 1 or below Sufficient organ functions as defined in the protocol Absence of earlier or present certain other conditions as defined in the protocol No pregnancy or lactation Women with childbearing potential must accept the use of adequate contraception throughout the study period Written informed consent

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Open label<br>Single arm pazopanib | Drug: Pazopanib<br>* Two (2) tablets of 400 mg given once daily continuously<br>* Other names: Votrient;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate | The ratio of patients with CR (complete remission) + PR (partial remission) + SD (stable disease) at week 12 after start of treatment | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | Progression free survival (KM analysis) for all patients administered the study drug | The patients will be followed for the duration of the trial treatment, an expected average of 6 months | 
| DCR in relation to mutation | Disease control rate as described above in relation to the type of mutation of the primary tumor if this is available (not mandatory) | Week 12 | 
| DCR in relation to plasma concentration | Disease control rate as defined above in relation to the trough level (plasma concentration) of the study drug at week 12 | Week 12 | 
| Toxicity | Recording of adverse events including SAE/SAR for all patients administered the study drug | The patients will be followed for the duration of the trial treatment + 1 month, an expected average of 7 months | 
| Overall response rate | ORR = CR+PR at the time of best response during the study period | The patients will be followed for the duration of the trial treatment, an expected average of 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical trial, Investigational drugs, Gastrointestinal stromal tumors, Pazopanib