Pazopanib in Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib - Full Text View

Purpose

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	Intervention	Phase
Gastrointestinal Stromal Tumors	Drug: Pazopanib	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: gastrointestinal stromal tumor

MedlinePlus related topics: Cancer Soft Tissue Sarcoma

Drug Information available for: Imatinib Pazopanib Sunitinib

Genetic and Rare Diseases Information Center resources: Gastrointestinal Stromal Tumors Malignant Mesenchymal Tumor Soft Tissue Sarcoma

U.S. FDA Resources

Further study details as provided by Scandinavian Sarcoma Group:

Primary Outcome Measures:

Disease control rate [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
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) [ Time Frame: The patients will be followed for the duration of the trial treatment, an expected average of 6 months ] [ Designated as safety issue: No ]
Progression free survival (KM analysis) for all patients administered the study drug
DCR in relation to mutation [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
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 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Disease control rate as defined above in relation to the trough level (plasma concentration) of the study drug at week 12
Toxicity [ Time Frame: The patients will be followed for the duration of the trial treatment + 1 month, an expected average of 7 months ] [ Designated as safety issue: Yes ]
Recording of adverse events including SAE/SAR for all patients administered the study drug
Overall response rate [ Time Frame: The patients will be followed for the duration of the trial treatment, an expected average of 6 months ] [ Designated as safety issue: No ]
ORR = CR+PR at the time of best response during the study period


Estimated Enrollment:	72
Study Start Date:	February 2012
Estimated Study Completion Date:	September 2016
Primary Completion Date:	January 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Open label Single arm pazopanib	Drug: Pazopanib Two (2) tablets of 400 mg given once daily continuously Other Name: Votrient

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01524848

Locations


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

Sponsors and Collaborators

Scandinavian Sarcoma Group

GlaxoSmithKline

Investigators


Principal Investigator:	Mikael Eriksson, MD PhD	Scandinavian Sarcoma Group

More Information


Responsible Party:	Scandinavian Sarcoma Group
ClinicalTrials.gov Identifier:	NCT01524848 History of Changes
Other Study ID Numbers:	SSG XXI
Study First Received:	January 24, 2012
Last Updated:	May 2, 2016
Health Authority:	Sweden: Medical Products Agency Norway: Norwegian Medicines Agency Denmark: Danish Medicines Agency Finland: Finnish Medicines Agency Iceland: Icelandic Medicines Control Agency

Keywords provided by Scandinavian Sarcoma Group:


Clinical trial Investigational drugs Gastrointestinal stromal tumors Pazopanib

Additional relevant MeSH terms:


Gastrointestinal Stromal Tumors Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases Gastrointestinal Diseases Sunitinib	Imatinib Mesylate Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors

ClinicalTrials.gov processed this record on September 30, 2016

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