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PAZOPANIB Efficacy and Tolerance in Desmoids Tumors : Phase 2 Clinical Trial

Phase 2
18 Years
Open (Enrolling)
Progressive Desmoids Tumors

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Trial Information

PAZOPANIB Efficacy and Tolerance in Desmoids Tumors : Phase 2 Clinical Trial

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 94 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;

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

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. Known allergy to Pazopanib, Methotrexate or vinblastine;

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

4. 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.

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

1. Malabsorption;

2. Major resection of small intestine or stomach.

6. Active uncontrolled infectious disease;

7. Corrected QT interval> 480 ms;

8. 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.

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

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

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

12. 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;

13. Evidence of active bleeding or bleeding tendency;

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

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

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

17. Severe renal dysfunction;

18. Severe hepatic dysfunction;

19. History of psoriasis, rheumatoid arthritis, alcoholism, illness or chronic liver

20. 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;

21. 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;

22. 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).

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

24. Pregnancy and lactation

25. 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

4. Phenylbutazone,

5. Yellow fever vaccine.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Efficacy evaluation in terms of non progression rate at 6 months of treatment with Pazopanib

Outcome Description:

Non progression rate at 6 months (RECIST v.1.1, Annex I)

Outcome Time Frame:

6 month

Safety Issue:


Principal Investigator


Investigator Role:

Study Chair

Investigator Affiliation:

Institut Bergonié


France: National Security Agency of Medicines and Health Products

Study ID:




Start Date:

July 2012

Completion Date:

July 2016

Related Keywords:

  • Progressive Desmoids Tumors
  • Desmoids tumors
  • Pazopanib
  • Phase 2 clinical trial
  • Cross over
  • Fibromatosis, Aggressive