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

Primary Purpose

Gastrointestinal Stromal Tumors

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pazopanib
Sponsored by
Scandinavian Sarcoma Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastrointestinal Stromal Tumors focused on measuring Clinical trial, Investigational drugs, Gastrointestinal stromal tumors, Pazopanib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Aarhus University Hospital, dept. of Oncology
  • Herlev Hospital, dept. of Oncology
  • Helsinki University Hospital, dept. of oncology
  • Kuopio University Hospital Cancer Center
  • Klinik für Interdisziplinäre Onkologie, Sarkomzentrum Berlin-Brandenburg
  • Universitätsklinikum Essen, Innere klinik und Poliklinik
  • Studienzentrale chirurgische klinik, Universitäts medizin Mannheim
  • Dept of Oncology, Haukeland University Hospital
  • Norwegian Radium Hospital
  • Dept of Oncology, St Olav Hospital
  • Dept of Oncology, Sahlgrenska University Hospital
  • Dept of Oncology, Linköping University Hospital
  • Dept of Oncology, Skane University Hospital
  • Radiumhemmet, Karolinska University Hospital
  • Dept of Oncology, Norrland University Hospital
  • Dept of Oncology, Academic Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Open label

Arm Description

Single arm pazopanib

Outcomes

Primary Outcome Measures

Disease control rate
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)
Progression free survival (KM analysis) for all patients administered the study drug
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)
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
Toxicity
Recording of adverse events including SAE/SAR for all patients administered the study drug
Overall response rate
ORR = CR+PR at the time of best response during the study period

Full Information

First Posted
January 24, 2012
Last Updated
May 9, 2017
Sponsor
Scandinavian Sarcoma Group
Collaborators
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT01524848
Brief Title
Pazopanib in Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib
Acronym
PAGIST
Official Title
Pazopanib in Advanced GISTs Refractory to Imatinib and Sunitinib - A Non-comparative Phase II Multicenter Study by the Scandinavian Sarcoma Group
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Scandinavian Sarcoma Group
Collaborators
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Stromal Tumors
Keywords
Clinical trial, Investigational drugs, Gastrointestinal stromal tumors, Pazopanib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Open label
Arm Type
Other
Arm Description
Single arm pazopanib
Intervention Type
Drug
Intervention Name(s)
Pazopanib
Other Intervention Name(s)
Votrient
Intervention Description
Two (2) tablets of 400 mg given once daily continuously
Primary Outcome Measure Information:
Title
Disease control rate
Description
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 Outcome Measure Information:
Title
Progression free survival (PFS)
Description
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
Title
DCR in relation to mutation
Description
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
Title
DCR in relation to plasma concentration
Description
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
Title
Toxicity
Description
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
Title
Overall response rate
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mikael Eriksson, MD PhD
Organizational Affiliation
Scandinavian Sarcoma Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aarhus University Hospital, dept. of Oncology
City
Aarhus
ZIP/Postal Code
DK-8000 Aarhus C
Country
Denmark
Facility Name
Herlev Hospital, dept. of Oncology
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Helsinki University Hospital, dept. of oncology
City
Helsingfors
ZIP/Postal Code
FI-00029
Country
Finland
Facility Name
Kuopio University Hospital Cancer Center
City
Kuopio
ZIP/Postal Code
FI-70029
Country
Finland
Facility Name
Klinik für Interdisziplinäre Onkologie, Sarkomzentrum Berlin-Brandenburg
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Universitätsklinikum Essen, Innere klinik und Poliklinik
City
Essen
ZIP/Postal Code
DE-45122
Country
Germany
Facility Name
Studienzentrale chirurgische klinik, Universitäts medizin Mannheim
City
Mannheim
ZIP/Postal Code
DE-68167
Country
Germany
Facility Name
Dept of Oncology, Haukeland University Hospital
City
Bergen
ZIP/Postal Code
N-5021
Country
Norway
Facility Name
Norwegian Radium Hospital
City
Oslo
ZIP/Postal Code
N-0310
Country
Norway
Facility Name
Dept of Oncology, St Olav Hospital
City
Trondheim
ZIP/Postal Code
N-7006
Country
Norway
Facility Name
Dept of Oncology, Sahlgrenska University Hospital
City
Gothenburg
ZIP/Postal Code
SE-413 45
Country
Sweden
Facility Name
Dept of Oncology, Linköping University Hospital
City
Linköping
ZIP/Postal Code
SE-581 85
Country
Sweden
Facility Name
Dept of Oncology, Skane University Hospital
City
Lund
ZIP/Postal Code
SE-221 85
Country
Sweden
Facility Name
Radiumhemmet, Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
SE-171 76
Country
Sweden
Facility Name
Dept of Oncology, Norrland University Hospital
City
Umeå
ZIP/Postal Code
SE-901 85
Country
Sweden
Facility Name
Dept of Oncology, Academic Hospital
City
Uppsala
ZIP/Postal Code
SE-751 85
Country
Sweden

12. IPD Sharing Statement

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Pazopanib in Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib

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