Phase I trial of concurrent sunitinib and radiation therapy as preoperative treatment for soft tissue sarcoma.

introductionAlthough the introduction of multimodal treatment of soft tissue sarcoma improved local tumour control, local failure still occurs in a good number of patients. Therefore, further improvement of current treatment strategies is necessary. The proposed study treatment will combine standard external beam radiation and the orally administered receptor tyrosine kinase inhibitor sunitinib. METHODS AND ANALYSIS: Patients with soft tissue sarcoma will receive sunitinib and irradiation as neoadjuvant treatment. Radiotherapy will be administered as intensity modulated radiation therapy with a total dose of 50.4 Gy in 28 fractions (5 1/2 weeks). Patients will receive sunitinib daily for 2 weeks prior to and then concurrently with irradiation. Sunitinib will be given in two dose levels. The first dose level will be 25 mg sunitinib per os daily. The second dose level will be 37.5 mg. A dose modification schedule according to a 3+3 design will be applied. Restaging and tumour resection will be performed 6 weeks after completion of sunitinib and irradiation. Primary outcome measures will be the dose-limiting toxicity and maximal tolerated dose of sunitinib administered concurrently with irradiation. Toxicity of the study treatment will be documented according to Common Terminology Criteria of Adverse Events (CTCAE) 4.0. Secondary outcome measures will be the response to the study treatment and morbidity of the tumour resection. Imaging response will be determined according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria comparing MRI performed prior to and 6 weeks after completion of study treatment. Pathological response will be determined evaluating the fraction of non-viable tumour in the resection specimen. Resection morbidity will be evaluated according to CTCAE 4.0. ETHICS AND DISSEMINATION: Approval was obtained from the ethics committee II of the University of Heidelberg, Germany (Reference number 2011-064F-MA). Furthermore, the study was approved by the German Federal Institute for Drugs and Medical Devices (Reference number 4037708). TRIAL REGISTRATION EUDRACT: 2007-002864-87 Clinicaltrials.gov: NCT01498835.