Gastrointestinal Stromal Tumors
Conditions
Keywords
Clinical trial, Investigational drugs, Gastrointestinal stromal tumors, Pazopanib
Brief summary
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.
Interventions
DRUGPazopanib
Two (2) tablets of 400 mg given once daily continuously
Sponsors
GlaxoSmithKline
Scandinavian Sarcoma Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate | Week 12 | The ratio of patients with CR (complete remission) + PR (partial remission) + SD (stable disease) at week 12 after start of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | The patients will be followed for the duration of the trial treatment, an expected average of 6 months | Progression free survival (KM analysis) for all patients administered the study drug |
| DCR in relation to mutation | Week 12 | Disease control rate as described above in relation to the type of mutation of the primary tumor if this is available (not mandatory) |
| DCR in relation to plasma concentration | Week 12 | Disease control rate as defined above in relation to the trough level (plasma concentration) of the study drug at week 12 |
| Toxicity | The patients will be followed for the duration of the trial treatment + 1 month, an expected average of 7 months | Recording of adverse events including SAE/SAR for all patients administered the study drug |
| Overall response rate | The patients will be followed for the duration of the trial treatment, an expected average of 6 months | ORR = CR+PR at the time of best response during the study period |
Countries
Denmark, Finland, Germany, Norway, Sweden
Outcome results
None listed