Pazopanib in Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib

Scandinavian Sarcoma Group72 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gastrointestinal Stromal Tumors

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (16)

Aarhus University Hospital, dept. of Oncology

Aarhus, Denmark

Herlev Hospital, dept. of Oncology

Herlev, Denmark

Helsinki University Hospital, dept. of oncology

Helsingfors, Finland

Kuopio University Hospital Cancer Center

Kuopio, Finland

Klinik für Interdisziplinäre Onkologie, Sarkomzentrum Berlin-Brandenburg

Berlin, Germany

Universitätsklinikum Essen, Innere klinik und Poliklinik

Essen, Germany

Studienzentrale chirurgische klinik, Universitäts medizin Mannheim

Mannheim, Germany

Dept of Oncology, Haukeland University Hospital

Bergen, Norway

Norwegian Radium Hospital

Oslo, Norway

Dept of Oncology, St Olav Hospital

Trondheim, Norway

...and 6 more locations

Outcomes

Primary Outcomes

Disease control rate

The ratio of patients with CR (complete remission) + PR (partial remission) + SD (stable disease) at week 12 after start of treatment

Time frame: Week 12

Secondary Outcomes

Progression free survival (PFS)

Progression free survival (KM analysis) for all patients administered the study drug

Time frame: 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)

Time frame: 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

Time frame: Week 12

Toxicity

Recording of adverse events including SAE/SAR for all patients administered the study drug

Time frame: 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

Time frame: The patients will be followed for the duration of the trial treatment, an expected average of 6 months