Pazopanib in Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib

NCT01524848 | Completed Phase 2 DMC

• 1 other identifier: SSG XXI
• Study Type: interventional
• Target: 72
• Locations: 5 countries
• Sites: 16

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.

Conditions

Gastrointestinal Stromal Tumors

Keywords

Clinical trial; Investigational drugs; Gastrointestinal stromal tumors; Pazopanib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Progression free survival (PFS)

  The patients will be followed for the duration of the trial treatment, an expected average of 6 months

• DCR in relation to mutation

  Week 12

• DCR in relation to plasma concentration

  Week 12

• Toxicity

  The patients will be followed for the duration of the trial treatment + 1 month, an expected average of 7 months

• Overall response rate

  The patients will be followed for the duration of the trial treatment, an expected average of 6 months

Study Arms (1)

Open label

OTHER

Single arm pazopanib

Drug: Pazopanib

Interventions

Pazopanib DRUG

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

Also known as: Votrient

Open label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Scandinavian Sarcoma Group: lead
• GlaxoSmithKline: collaborator

Study Sites (16)

Aarhus University Hospital, dept. of Oncology

Aarhus, DK-8000 Aarhus C, Denmark

Location

Herlev Hospital, dept. of Oncology

Herlev, 2730, Denmark

Location

Helsinki University Hospital, dept. of oncology

Helsingfors, FI-00029, Finland

Location

Kuopio University Hospital Cancer Center

Kuopio, FI-70029, Finland

Location

Klinik für Interdisziplinäre Onkologie, Sarkomzentrum Berlin-Brandenburg

Berlin, 13125, Germany

Location

Universitätsklinikum Essen, Innere klinik und Poliklinik

Essen, DE-45122, Germany

Location

Studienzentrale chirurgische klinik, Universitäts medizin Mannheim

Mannheim, DE-68167, Germany

Location

Dept of Oncology, Haukeland University Hospital

Bergen, N-5021, Norway

Location

Norwegian Radium Hospital

Oslo, N-0310, Norway

Location

Dept of Oncology, St Olav Hospital

Trondheim, N-7006, Norway

Location

Dept of Oncology, Sahlgrenska University Hospital

Gothenburg, SE-413 45, Sweden

Location

Dept of Oncology, Linköping University Hospital

Linköping, SE-581 85, Sweden

Location

Dept of Oncology, Skane University Hospital

Lund, SE-221 85, Sweden

Location

Radiumhemmet, Karolinska University Hospital

Stockholm, SE-171 76, Sweden

Location

Dept of Oncology, Norrland University Hospital

Umeå, SE-901 85, Sweden

Location

Dept of Oncology, Academic Hospital

Uppsala, SE-751 85, Sweden

Location

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Study Officials

• Mikael Eriksson, MD PhD

  Scandinavian Sarcoma Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2012
• First Posted: February 2, 2012
• Study Start: February 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: November 1, 2016
• Last Updated: May 10, 2017

Record last verified: 2016-05

Locations

FI (2); SE (6); NO (3); DK (2); DE (3)