Translational study Of Pre-operative Pazopanib in Sarcomas (TOPPS)

• Research type

  Research Study

• Full title

  A Translational, proof of the concept, study Of Pre-operative Pazopanib in treatment-naive patients with resectable soft tissue Sarcomas (TOPPS)

• IRAS ID

  62625

• Sponsor organisation

  The Royal Marsden NHS Foundation Trust

• Eudract number

  2010-022416-40

• ISRCTN Number

  N/A

• Clinicaltrials.gov Identifier

  N/A

• Research summary

  Soft Tissue Sarcoma (STS) is a group of rare and heterogeneous connective tissue cancers which include multiple histological subtypes. The 5-year survival in Europe for adult STS averages 60%. Surgery is usually the only curative treatment and post-operative radiotherapy helps to prevent local recurrence. However, local control has no impact on the development of metastases which are more likely in patients with large, high-grade (more aggressive) tumours. Adjuvant chemotherapy may in some circumstances prolong time to disease progression but does not increase overall survival. Angiogenesis (the formation of new blood vessels) is needed for the growth and dissemination of sarcomas. Several small molecule inhibitors of Vascular Endothelial Growth Factor Receptors (VEGFR), key regulators of angiogenesis, have shown activity in refractory metastatic sarcomas, including pazopanib, which has been tested in a large randomized Phase III trial in metastatic STS following demonstration of activity in phase II. It is hypothesized that angiogenesis inhibitors may modulate local and micromestastatic tumor growth and may reduce the inflammatory and pro-angiogenic effects of surgery when given prior to operation. The TOPPS study is a proof of concept study that aims to investigate the antiangiogenic and antitumour effects of pazopanib in a preoperative setting. All patients will take 800 mg of pazopanib once daily for a maximum of 28 days before surgery. Vascular responses will be evaluated using functional magnetic resonance imaging scans. Secondary and exploratory aims of this study will include the evaluation of tumor responses using conventional radiologic criteria and tumor biopsies, as well as the investigation of other tumor and blood-borne biomarkers. After surgery, patients may continue adjuvant pazopanib for 12 months. A total of 30 evaluable patients, age 18 and over, with histologically confirmed and resectable soft tissue sarcomas arising from extremities will be enrolled in this study.

• REC name

  London - West London & GTAC Research Ethics Committee

• REC reference

  11/LO/0891

• Date of REC Opinion

  30 Sep 2011

• REC opinion

  Further Information Favourable Opinion