Pazopanib in Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib (PAGIST)

Scandinavian Sarcoma Group

Status and phase

Completed

Phase 2

Conditions

Gastrointestinal Stromal Tumors

Treatments

Drug: Pazopanib

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01524848

SSG XXI

Details and patient eligibility

About

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.

Enrollment

72 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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