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

• ClinicalTrials.gov Identifier: NCT01524848
• Recruitment Status: Completed
• First Posted: February 2, 2012
• Last Update Posted: May 10, 2017
• Sponsor: Scandinavian Sarcoma Group
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): Scandinavian Sarcoma Group

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 (Clinical Trial)
• Estimated 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: February 2012
• Actual Primary Completion Date: January 2015
• Actual Study Completion Date: November 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Disease control rate [ Time Frame: 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 :

1. Progression free survival (PFS) [ Time Frame: 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
2. DCR in relation to mutation [ Time Frame: 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)
3. DCR in relation to plasma concentration [ Time Frame: Week 12 ]
   Disease control rate as defined above in relation to the trough level (plasma concentration) of the study drug at week 12
4. Toxicity [ Time Frame: 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
5. Overall response rate [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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
• Other Study ID Numbers: SSG XXI
• First Posted: February 2, 2012
• Last Update Posted: May 10, 2017
• Last Verified: May 2016

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