The purpose of this study is to determine the safety of continuous dosing of sunitinib in association with radiotherapy in patients with non GIST (gastro intestinal stromal tumor) sarcomas who cannot be treated by surgery.

The primary objective of the study is to determine the maximum tolerated dose (MTD) of continuous dosing of sunitinib in association with radiotherapy in patients with non GIST sarcomas who cannot be treated by surgery.

This study is a multicentre, open-label phase I with dose escalation : 2 dose levels.

3-6 patients will be included at each dose level.3-18 patients will be included in the study.

Study design : 2 dose levels

Step 1 : 25 mg once daily Step 2 : 37.5 mg once daily

3-6 patients will be included at each of the sunitinib dose levels, depending on the number of DLTs (dose limiting toxicity) occurring in 14 weeks after start of treatment

DLT is defined as :

any grade 3 or 4 musculoskeletal or cutaneous toxicity within the field of radiation any other toxicity > or = 4

Secondary objectives are :

• to evaluate the safety with late toxicities
• to estimate the response rate at 6 months
• to estimate the progression free survival
• to evaluate the proportion of patients with an operable tumour after treatment

Exploratory objectives are :

• to study evolution during treatment of neo-angiogenesis measured by dynamic contrast enhanced-ultrasonography (DCE-US)
• to study the correlation between clinical response and changes of tumor perfusion measured by DCE-US

Inclusion Criteria:

1. Male or female patients > 18 years of age

2. Histologically or cytologically (in case of recurrence) confirmed connective tissue neoplasm, including any of the following subtypes:

   • Liposarcomas
   • Fibrosarcoma, myxofibrosarcoma
   • Undifferentiated pleomorphic sarcoma
   • Leiomyosarcomas
   • Pleomorphic rhabdomyosarcomas only
   • Angiosarcomas
   • Uncertain differentiated tumors: synovial sarcomas, epithelioid sarcomas, alveolar sarcomas, clear cells sarcomas.

   or osteosarcoma diagnosis, chondrosarcoma or chordoma.

3. Locally advanced or locally recurrent inoperable tumor without previous irradiation [inoperable status must be assessed by staff including a surgeon specialized in sarcoma].

4. No prior treatment by sunitinib malate

5. Life expectancy > 6 months

6. ECOG performance status ≤ 2

7. Blood tests, renal and liver functions in the normal range with, in the 7 days prior to study entry, blood or serum values as follows:

   • Absolute neutrophil count ≥ 1.,5 G/L
   • Platelet count ≥ 100 G/L
   • Bilirubin ≤ 1.5 mg/dL
   • PT and INR ≤ 1.5 times upper limit of normal [Patients under preventive anticoagulant therapy are allowed to participate]
   • AST and ALT ≤ 2.5 times upper limit of normal
   • Creatinine ≤ 150 umol/L
   • Calcium ≤ 12 mg/dL
   • Blood glucose < 150 mg/dL

8. Fertile patients must use effective contraception prior to, during, and for 28 days after completion of study therapy

9. Ability to swallow oral medications

10. Mandatory affiliation with a health insurance company

11. Signed written informed consent.

Exclusion Criteria:

1. GIST, Ewing sarcoma or embryonic rhabdomyosarcomas

2. Radiation field including lung, bowel, or central nervous system

3. Pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication

4. NCI grade ≥ 3 hemorrhage within the past 4 weeks prior to study drug administration

5. Significant cardiovascular disease (New York Heart Association (NYHA) > grade 2 congestive cardiac failure, myocardial infarction within 6 months prior to inclusion, unstable angina, severe cardiac arrhythmia, severe cerebrovascular accident within 6 months prior to inclusion, history of severe thromboembolism (pulmonary embolism or deep vein thrombosis DVT) within 6 months prior to inclusion (patients with recent history of DVT treated by anticoagulant (except therapeutic warfarin)during at least 6 weeks are eligibles), prolonged QTc interval (QTc > 480 msec with Bazett), bradycardia (heart rate < 45bpm), electrolytic troubles (hyponatremia<120mmol/l, kalemia≥6mmol/l) or uncontrolled hypertension while receiving appropriate medication (≥ 160 mm Hg systolic and/or ≥ 90 mm Hg diastolic).

6. Less than 6 weeks between prior neoplastic treatment by tyrosine kinase inhibitor and inclusion and less than 4 weeks for other neoplastic treatments

7. Major surgical procedure, open biopsy, or serious non healing wound within 28 days prior to first day of treatment

8. Concurrent participation in another clinical trial

9. Other disease or illness within the past 6 months prior to study drug administration, including the following:

   • Psychiatric illness or social situation that would preclude study compliance
   • Known human immunodeficiency virus (HIV)- or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection

10. Known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease

11. peritoneal carcinosis

12. number of metastatic sites > 2

13. Restriction of freedom by judicial or administrative decision

14. Pregnant or lactating women