Desmoids tumors are benign soft tissues tumors characterized by aggressiveness and potential local recurrence. There is a female predominance with a sex ratio of 2/1 and median age at diagnosis is about 30 years.

Only a complete surgical excision is recommended in desmoids tumors. Some forms of desmoid tumors are recurrent and/or symptomatic and are not accessible to a conservative surgical treatment. In these clinical situations, only a medical treatment may achieve tumor control and quality of life maintenance. Place of systemic treatments in the management of desmoids tumors is poorly evaluated. Regarding chemotherapy, methotrexate and vinblastine protocol is actually the best evaluated combination, which allowed observing objective response rate between 40 and 75%. Toxicity was mainly marked by the risk of haematological toxicity.

Pazopanib is an inhibitor of multi-target tyrosine kinase, in oral form, with selective type receptors -1, -2 and -3 of VEGF receptors on the PDGFA and B, and c-Kit. It is currently under clinical development in humans in the treatment of several tumor types.

This is a Phase II, randomized, multicenter, open label trial, evaluating efficacy and safety of pazopanib versus a chemotherapy protocol combining methotrexate and vinblastine in progressive and symptomatic desmoid tumors.

This study will include 72 patients in 15 centers of the French Sarcoma Group.

Patients will be treated according to therapeutic strategy allocated by randomization until documented RECIST progression and for a maximum of 12 months :

• Arm A = experimental strategy: daily oral administration of pazopanib.
• Arm B = reference strategy: methotrexate-vinblastine.

In case of documented radiological progression (RECIST criteria):

• Patients initially included in arm A will have the opportunity, as determined by the investigator, to receive arm B treatment, or leave the study,
• Patients initially included in arm B will have the opportunity, as determined by the investigator, to receive arm A treatment, or leave the study.

Inclusion Criteria:

1. Written consent;

2. Age ≥ 18 years;

3. ECOG ≤ 1;

4. Histologically confirmed desmoid tumor;

5. Disease progression before the patient's inclusion : completion of two similar imaging obtained within 6 months apart (a tolerance of 6 weeks is accepted)

6. Measurable target lesion (RECIST criteria) ;

7. Left ventricular ejection fraction (MUGA or ECHO) within the normal;

8. Normal hematological, renal and liver functions :

   1. Hemoglobin ≥ 9 g / dl; neutrophils ≥ 1.5 x 109 / l; platelets ≥ 100 x 109 / l; prothrombin time or INR1 ≤ 1.2 ULN or activated partial thromboplastin time ≤ 1.2 ULN;
   2. Amino alanine transferase and aspartate amino transferase ≤ 2.5 ULN;
   3. Total bilirubin ≤ 1.5 ULN;
   4. Creatinine ≤ 1.5 mg/dl or, if creatinine> 1.5 mg/dl, Creatinine clearance ≥ 50 m/min;
   5. Urinary protein / urinary creatinine (Pu / Cu) <1. If PU/Cu ≥ 1, patients must have a proteinuria below 1g/24 h

9. Women are eligible provided they:

   1. Physiologically incapable of childbearing (hysterectomy, oophorectomy, bilateral tubal ligation, menopause).
   2. Of childbearing age if they have had a negative pregnancy test in the week before the first dose of treatment.
   3. Women of childbearing potential and men must agree to take an adequate method of contraception. Permitted contraceptive methods : IUD with a documented failure rate of 1% per year, Partner's vasectomy, complete sex abstinence (for 14 days before inclusion, the test period and after cessation of treatment according to the chemotherapy as described below), dual contraception, oral contraceptives.

   Effective contraception must be implemented:

   • Up to 6 months after treatment with vinblastine
   • Up to 5 months after treatment with Methotrexate for men and up to 3 months after treatment with Methotrexate for women
   • For the duration of treatment with Pazopanib;

10. Affiliated to a social security system

Exclusion Criteria:

1. Personal history of malignancy except:

   1. Cervical intraepithelial neoplasia;
   2. Skin basal cell carcinoma;
   3. Treated localized prostate carcinoma with PSA <1;
   4. Neoplasia treated with curative intent, in remission for at least five years and considered at low risk of relapse.

2. Pretreatement by Pazopanib or Methotrexate - vinblastine;

3. Known allergy to Pazopanib, Methotrexate or vinblastine;

4. Histological sampling not available for review or biological study;

5. Clinical abnormalities which may increase the risk of gastric bleeding (not exhaustive list);

   1. Gastric tumor with known risk of bleeding;
   2. Inflammatory bowel disease or other gastrointestinal disease may increase the risk of gastric perforation.

6. Pathologies that can lead to impaired intestinal absorption (not exhaustive):

   1. Malabsorption;
   2. Major resection of small intestine or stomach.

7. Active uncontrolled infectious disease;

8. Corrected QT interval> 480 ms;

9. History of cardiovascular disease in the last 6 months:

   1. Cardiac angioplasty;
   2. Myocardial infarction;
   3. Unstable angina;
   4. Bypass surgery;
   5. Symptomatic arterial disease.

10. Congestive heart failure grade II, III or IV according to the New York Hearth Association (NYHA) classification;

11. Uncontrolled arterial hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);

12. History of stroke or transient ischemic attack, pulmonary embolism or deep vein thrombosis not treated, within 6 months;

13. History of major surgery or trauma within 28 days prior the first day of treatment, or presence of a wound, fracture or non-healed ulcer;

14. Evidence of active bleeding or bleeding tendency;

15. Known endobronchial lesions and / or infiltrative lesions of the large vessels lung;

16. History of hemoptysis of more than 2.5 ml in the eight weeks preceding the first day of chemotherapy;

17. Pulmonary dysfunction, asthma, emphysema, chronic obstructive pulmonary bronchitis, pneumonia, pneumothorax, pulmonary contusion, hemothorax, distress acute respiratory syndrome, pulmonary fibrosis;

18. Severe renal dysfunction;

19. Severe hepatic dysfunction;

20. History of psoriasis, rheumatoid arthritis, alcoholism, illness or chronic liver dysfunction;

21. Any pre-existing severe or unstable medical or psychiatric condition, or other condition that may interfere with patient safety, the collection of its informed consent or adherence to treatment;

22. Patient who refused or could not stop taking banned drugs for at least 14 days (or 5 half-lives of the drug) before the first day of start of chemotherapy and for the duration of the study;

23. During cancer treatment:

    1. Radiotherapy, surgery or tumor embolization within 14 days before the 1st dose of pazobanib (arm A) or chemotherapy methotrexate, vinblastine (arm B);
    2. Chemotherapy, immunotherapy, biological treatment, experimental or hormone therapy within 14 days or 5 half-lives of medication before the first day of the pazopanib (arm A) or chemotherapy with methotrexate, vinblastine (arm B).

24. History of cancer treatment toxicity> grade 1 and / or whose the intensity increases, outside of alopecia.

25. Pregnancy and lactation

26. Concomitant treatment which can't be interrupted or replaced and which is not indicated with methotrexate:

    1. Probenecid (alone or associated with sulfamethoxazole),
    2. Trimethoprim,
    3. Acetylsalicylic acid (for methotrexate doses above 20 mg per week with the acetylsalicylic acid and used at doses analgesics or antipyretics (≥ 500 mg per dose and/or <3 g per day)or anti-inflammatory (≥ 1 g per dose and / or > 3 g per day),
    4. Phenylbutazone,
    5. Yellow fever vaccine.

2 years