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

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

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 Overview

• Status: Completed
• Conditions: Gastrointestinal Stromal Tumors
• Intervention / Treatment: Drug: Pazopanib

• Study Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Scandinavian Sarcoma Group
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Mikael Eriksson, MD PhD, Scandinavian Sarcoma Group

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: January 24, 2012
• First Submitted That Met QC Criteria: January 30, 2012
• First Posted (Estimate): February 2, 2012

Study Record Updates

• Last Update Posted (Actual): May 10, 2017
• Last Update Submitted That Met QC Criteria: May 9, 2017
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Clinical trial; Pazopanib; Gastrointestinal stromal tumors; Investigational drugs
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: SSG XXI