Pazopanib in Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib

Gastrointestinal Stromal Tumors Clinical Trial

— PAGIST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01524848
• Other study ID #: SSG XXI
• Status: Completed
• Phase: Phase 2
• First received: January 24, 2012
• Last updated: May 9, 2017
• Start date: February 2012
• Est. completion date: November 2016

Study information

• Verified date: May 2016
• Source: Scandinavian Sarcoma Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: November 2016
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors

Intervention

Drug:
• Pazopanib
Two (2) tablets of 400 mg given once daily continuously

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital, dept. of Oncology	Aarhus
Denmark	Herlev Hospital, dept. of Oncology	Herlev
Finland	Helsinki University Hospital, dept. of oncology	Helsingfors
Finland	Kuopio University Hospital Cancer Center	Kuopio
Germany	Klinik für Interdisziplinäre Onkologie, Sarkomzentrum Berlin-Brandenburg	Berlin
Germany	Universitätsklinikum Essen, Innere klinik und Poliklinik	Essen
Germany	Studienzentrale chirurgische klinik, Universitäts medizin Mannheim	Mannheim
Norway	Dept of Oncology, Haukeland University Hospital	Bergen
Norway	Norwegian Radium Hospital	Oslo
Norway	Dept of Oncology, St Olav Hospital	Trondheim
Sweden	Dept of Oncology, Sahlgrenska University Hospital	Gothenburg
Sweden	Dept of Oncology, Linköping University Hospital	Linköping
Sweden	Dept of Oncology, Skane University Hospital	Lund
Sweden	Radiumhemmet, Karolinska University Hospital	Stockholm
Sweden	Dept of Oncology, Norrland University Hospital	Umeå
Sweden	Dept of Oncology, Academic Hospital	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
Scandinavian Sarcoma Group	GlaxoSmithKline

Countries where clinical trial is conducted

Denmark,  Finland,  Germany,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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