Clinical trial NCT01524848: Pazopanib in Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib
Official title: Pazopanib in Advanced GISTs Refractory to Imatinib and Sunitinib - A Non-comparative Phase II Multicenter Study by the Scandinavian Sarcoma Group
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumors
Keywords: Clinical trial
Investigational drugs
Gastrointestinal stromal tumors
Pazopanib
Lead sponsor: Scandinavian Sarcoma Group
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2012-02-02
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Disease control rate
timeFrame: Week 12
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: The patients will be followed for the duration of the trial treatment, an expected average of 6 months
measure: DCR in relation to mutation
timeFrame: Week 12
measure: DCR in relation to plasma concentration
timeFrame: Week 12
measure: Toxicity
timeFrame: The patients will be followed for the duration of the trial treatment + 1 month, an expected average of 7 months
measure: Overall response rate
timeFrame: The patients will be followed for the duration of the trial treatment, an expected average of 6 months
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital, dept. of Oncology
city: Herlev
country: Denmark
facility: Herlev Hospital, dept. of Oncology
city: Helsingfors
country: Finland
facility: Helsinki University Hospital, dept. of oncology
city: Kuopio
country: Finland
facility: Kuopio University Hospital Cancer Center
city: Berlin
country: Germany
facility: Klinik für Interdisziplinäre Onkologie, Sarkomzentrum Berlin-Brandenburg
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Innere klinik und Poliklinik
city: Mannheim
country: Germany
facility: Studienzentrale chirurgische klinik, Universitäts medizin Mannheim
city: Bergen
country: Norway
facility: Dept of Oncology, Haukeland University Hospital
city: Oslo
country: Norway
facility: Norwegian Radium Hospital
city: Trondheim
country: Norway
facility: Dept of Oncology, St Olav Hospital
city: Gothenburg
country: Sweden
facility: Dept of Oncology, Sahlgrenska University Hospital
city: Linköping
country: Sweden
facility: Dept of Oncology, Linköping University Hospital
city: Lund
country: Sweden
facility: Dept of Oncology, Skane University Hospital
city: Stockholm
country: Sweden
facility: Radiumhemmet, Karolinska University Hospital
city: Umeå
country: Sweden
facility: Dept of Oncology, Norrland University Hospital
city: Uppsala
country: Sweden
facility: Dept of Oncology, Academic Hospital
Study officials:
affiliation: Scandinavian Sarcoma Group
name: Mikael Eriksson, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: