Sunitinib and Radiation in Patients With Resectable Soft-tissue Sarcoma
关键词
抽象
描述
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.
日期
| 最后验证: | 11/30/2010 |
| 首次提交: | 09/13/2008 |
| 提交的预估入学人数: | 09/14/2008 |
| 首次发布: | 09/15/2008 |
| 上次提交的更新: | 06/20/2011 |
| 最近更新发布: | 06/22/2011 |
| 实际学习开始日期: | 08/31/2008 |
| 预计主要完成日期: | 02/29/2012 |
| 预计完成日期: | 02/29/2016 |
状况或疾病
干预/治疗
Drug: Sunitinib malate
Radiation: Radiotherapy
相
资格标准
| 有资格学习的年龄 | 16 Years 至 16 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: - Histologically confirmed soft-tissue sarcoma suitable for neoadjuvant radiotherapy and surgery - minimum age 16 years - ECOG performance status =1 - life expectancy of greater than 6 months - patients must have normal organ and marrow function - no evidence of a bleeding or thrombotic tendency, and no evidence of arterial or venous thrombosis - not pregnant or breastfeeding - the ability to give written informed consent. Exclusion Criteria: - Soft-tissue sarcoma located in sites where radiotherapy is associated with significant exposure of abdominal viscera - patients with other invasive malignancies, with the exception of non-melanoma skin cancer, in the last 5 years - patients receiving any other therapeutic investigational agents - patients who are receiving concurrent treatment with any other anti-cancer therapy - evidence of distant metastases - uncontrolled intercurrent illness - patients who are pregnant or breast feeding. |
结果
主要结果指标
1. To determine the maximum dose of sunitinib at which the combination of sunitinib and radiotherapy pre-operatively is safe and tolerable. [Baseline; post-2 weeks sunitinib only administration; post-sunitinib and radiotherapy combination treatment; 12 weeks post-surgery]
次要成果指标
1. To estimate response rates for the combination of sunitinib and radiotherapy. [Baseline; post-2 weeks sunitinib only administration; post-sunitinib and radiotherapy combination treatment; and at surgery]
