NCT00753727

Sunitinib and Radiation in Patients With Resectable Soft-tissue Sarcoma

A Phase IB/II Study of Sunitinib in Combination With Neoadjuvant Radiation in Patients With Resectable Soft-tissue Sarcoma

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Sponsor: Australasian Sarcoma Study Group · Academic / Other
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

This research is being done with the aim of developing a more effective treatment than standard radiotherapy and surgery alone. Although standard treatment is frequently successful, some patients do not respond well to this treatment. Low oxygen levels in tumours, which may be a particular problem with sarcomas, are thought to be one factor that contributes to failure of radiotherapy. Sunitinib is a new drug that is active against cells with low oxygen levels. The combination of sunitinib and radiotherapy has shown promising results in other cancers. The purpose of this study is to find out whether treatment with a new drug, sunitinib, can increase the effectiveness of radiotherapy at killing cancer cells; to test the safety of the combination of sunitinib and radiotherapy.

Detailed description

The presence of hypoxia has been documented in soft-tissue sarcomas, where it may contribute to radioresistance. Combinations of radiosensitisers such as ifosfamide and doxorubicin with radiotherapy have demonstrated promise in sarcomas, but with significant toxicity. The rationale for this study is based on: * the frequency of hypoxia in soft-tissue sarcomas * the importance of radiotherapy in neoadjuvant treatment of soft-tissue sarcomas * targeting hypoxic vasculature with sunitinib * the single agent activity of sunitinib in soft-tissue sarcomas. This study will assess the feasibility and tolerability of the combination of sunitinib with standard preoperative radiotherapy. The surrogate endpoints of tumor necrosis and functional and RECIST imaging response will provide early evidence of response rate. Toxicities will be assessed both during chemoradiation and following surgery. The impact of treatment on the hypoxic component of the tumor will be investigated with F18 azamycin arabinoside PET scans. Because the combination of sunitinib and radiotherapy has not been studied before, we propose a phase Ib design with dose reductions in the event of excessive toxicity. Sunitinib treatment will precede the commencement of radiotherapy by 2 weeks because there is preclinical evidence that priming the tumor vasculature may increase synergy with radiotherapy, and because sunitinib may have single agent activity in sarcomas, including measurable effects on tumor vasculature. Because it is anticipated that the likelihood of complications attributable to the combination of sunitinib and radiotherapy will be small, the starting dose of sunitinib will be 50mg/day for the two week lead-in period and then 25mg for 5 weeks with concurrent radiotherapy.

Conditions

• Soft Tissue Sarcoma

Interventions

Type	Name	Description
DRUG	Sunitinib malate	Sunitinib dose 50 mg/day orally for 2 weeks prior to radiotherapy. Treatment Dose Levels during radiotherapy: Dose level 0: Sunitinib 50mg/day for 2 weeks prior to radiotherapy, followed by 25mg/day given concurrently with radiotherapy; Dose level 1: Sunitinib 50mg/day for 2 weeks prior to radiotherapy, followed by 37.5mg/day given concurrently with radiotherapy; Dose level -1: Sunitinib 37.5mg/day for 2 weeks prior to radiotherapy, followed by 37.5mg/day given concurrently with radiotherapy. Dose escalation/de-escalation: first 6 patients will be accrued at dose level 0. The dose levels at which subsequent patients will be accrued will be determined using a dose modification schedule.
RADIATION	Radiotherapy	Preoperative radiotherapy consisting of external beam radiotherapy at a dose of 50.4 Gy given in 28 fractions, five days a week, over five weeks and 3 days to the planning target volume.

Timeline

• Start date: 2008-09-01
• Primary completion: 2012-03-01
• Completion: 2016-03-01
• First posted: 2008-09-16
• Last updated: 2011-06-23

Locations

1 site across 1 country: Australia