Efficacy of Pazopanib in Gastrointestinal Stromal Tumors (GIST)
Condition: GIST
MeSH terms: Gastrointestinal Stromal Tumors
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to evaluate the antitumor activity of pazopanib in patients with
      metastatic and/or locally advanced unresectable Gastrointestinal Stromal Tumors (GIST)
      resistant to imatinib and sunitinib. This is a phase II, randomized, multicentre study.
    

Detailed description: 
      Complete resection, with or without associated anticancer therapy, is the standard treatment
      of GIST. Even though the prognosis of advanced GIST has been tremendously improved by the
      introduction of tyrosine kinase inhibitors (TKI-imatinib, sunitinib...), the vast majority of
      patients will develop secondary resistance to these agents. The therapeutic options for
      patients with advanced GIST with resistance (or intolerance) to imatinib and sunitinib remain
      very limited. Some new molecules are currently being evaluated in patients with metastatic or
      locally advanced - imatinib-resistant disease. Nilotinib, for instance, has been evaluated in
      phase I/II trials and compassionate use programs with a median progression-free survival
      (PFS) close to 3 months and a median overall survival close to 8.5 months. A phase III trial
      comparing nilotinib vs. best supportive care (BSC) +/- imatinib or sunitinib (investigators
      choice) has just been completed and results are pending. Another molecule, Sorafenib, has
      been evaluated in 4th line treatment in compassionate use studies, with a median PFS close to
      5 months and a median overall survival of 10-13 months. There are currently no recognized
      standard options after failure of 2nd line treatment, and the recently updated guidelines
      from the NCCN or ESMO (2009) suggest the possible reintroduction of TKI in an attempt to
      control the progression of sensitive cell clones.

      Pazopanib is a broad spectrum TKI targeting KIT, PDGFR and VEGFR which has been tested in
      phase II trials in advanced sarcomas and has demonstrated promising antitumor activity.
      Whether pazopanib would be useful in patients with GIST is not known.

      In the present study, we propose to analyze the antitumor activity of pazopanib in patients
      with GIST refractory to imatinib and sunitinib. The drug will be tested against BSC in a
      randomized setting, with possible crossing-over to the no-treatment arm.
    

Intervention name(s): Pazopanib; Best supportive care
Intervention type(s): Drug; Other
Intervention description(s): Pazopanib is administered orally at 800 mg/day (one dose every morning). A dose modification is possible in case of documented toxicity, according to specific algorithms.; Best supportive care according to the investigator's judgment (chemotherapy, immunotherapy, hormone therapy are not allowed).
Non-targeted radiation therapy is tolerated, as antalgic strategy. Surgery is tolerated in case of emergency.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: GIST; Resistant; Pazopanib; Tyrosine kinase inhibitor; Best supportive care; Progression-free survival; Overall survival; Objective response rate; Best response; Tolerance profile