NCT01323400

Efficacy of Pazopanib in Gastrointestinal Stromal Tumors (GIST)

A Phase II Randomized Multicentre Study Evaluating the Efficacy of Pazopanib+Best Supportive Care (BSC) Versus BSC Alone in Metastatic and/or Locally Advanced Unresectable GIST, Resistant to Imatinib and Sunitinib

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 81 (actual)
• Sponsor: Centre Leon Berard · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

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.

Conditions

• GIST

Interventions

Type	Name	Description
DRUG	Pazopanib	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.
OTHER	Best supportive care	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.

Timeline

• Start date: 2011-03-01
• Primary completion: 2014-04-01
• Completion: 2016-02-01
• First posted: 2011-03-25
• Last updated: 2016-02-25

Locations

13 sites across 1 country: France