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

Sponsor

Scandinavian Sarcoma Group (Other)

Overall Status

Completed

CT.gov ID

NCT01524848

Collaborator

GlaxoSmithKline (Industry)

Enrollment

Locations

Arm

Duration (Months)

4.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Stromal Tumors	Drug: Pazopanib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Jan 1, 2015

Actual Study Completion Date :

Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Other: Open label Single arm pazopanib	Drug: Pazopanib Two (2) tablets of 400 mg given once daily continuously Other Names: Votrient

Arm

Intervention/Treatment

Other: Open label

Single arm pazopanib

Drug: Pazopanib

Two (2) tablets of 400 mg given once daily continuously

Other Names:

Votrient

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Aarhus University Hospital, dept. of Oncology	Aarhus	Denmark	DK-8000 Aarhus C
2	Herlev Hospital, dept. of Oncology	Herlev	Denmark	2730
3	Helsinki University Hospital, dept. of oncology	Helsingfors	Finland	FI-00029
4	Kuopio University Hospital Cancer Center	Kuopio	Finland	FI-70029
5	Klinik für Interdisziplinäre Onkologie, Sarkomzentrum Berlin-Brandenburg	Berlin	Germany	13125
6	Universitätsklinikum Essen, Innere klinik und Poliklinik	Essen	Germany	DE-45122
7	Studienzentrale chirurgische klinik, Universitäts medizin Mannheim	Mannheim	Germany	DE-68167
8	Dept of Oncology, Haukeland University Hospital	Bergen	Norway	N-5021
9	Norwegian Radium Hospital	Oslo	Norway	N-0310
10	Dept of Oncology, St Olav Hospital	Trondheim	Norway	N-7006
11	Dept of Oncology, Sahlgrenska University Hospital	Gothenburg	Sweden	SE-413 45
12	Dept of Oncology, Linköping University Hospital	Linköping	Sweden	SE-581 85
13	Dept of Oncology, Skane University Hospital	Lund	Sweden	SE-221 85
14	Radiumhemmet, Karolinska University Hospital	Stockholm	Sweden	SE-171 76
15	Dept of Oncology, Norrland University Hospital	Umeå	Sweden	SE-901 85
16	Dept of Oncology, Academic Hospital	Uppsala	Sweden	SE-751 85