Neoplasms

All Conditions

Behaviors and Mental Disorders

Skin and Connective Tissue Diseases

Rare Diseases

Fibromatosis, Aggressive

Aggression

Fibroma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Oculocerebral Syndrome With Hypopigmentation

Desmoid Tumor

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Methotrexate

Vinblastine

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Tubulin Modulators

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

Pazopanib

* 800 mg per day
* oral administration
* at least 1 hour before or 2 hours after a meal,
* until disease progression or for 12 months maximum

vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.

PAZOPANIB treatment

Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.

Active Comparator: Vinblastine and Methotrexate

ITALIANO Antoine, MD

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.

PAZOPANIB Efficacy and Tolerance in Desmoids Tumors

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

Percentage of patients remaining alive and progression-free at 6 months as per RECIST 1.1 after the day of randomisation.

Progression is defined using New Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), or a unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.

Best overall response is defined as the best response across all time points (RECIST v1.1). The best overall response is determined once all the data for the participant is known.

Each patient has been assigned one of the following categories (RECIST 1.1): complete response (disappearance of all target lesions); partial response (\>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); progression (20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and stable disease (nor CR, PR or progression).

Progression-free survival (PFS) defined as the time from randomization to the first documented progression (as per RECIST v1.1) or death (due to any cause), whichever occurs first. Patients alive and progression free were censored at the date of last follow-up, death, or last patient contact. Progression is assessed as per RECIST v1.1. Progression-free survival is estimated as a function of time using Kaplan-Meier method.

1- and 2-year PFS rates were reported.

Overall survival (OS) defined as the time from randomization to death (due to any cause). Patients alive were censored at the date of last follow-up or last patient contact. Overall survival was estimated as a function of time using Kaplan-Meier method.1- and 2-Year OS rates were reported.

Institut Bergonié

Pazopanib

* 800 mg per day
* oral administration
* at least 1 hour before or 2 hours after a meal,
* until disease progression or for 12 months maximum

PAZOPANIB treatment: Pazopanib

* 800 mg per day
* oral administration
* at least 1 hour before or 2 hours after a meal,
* until disease progression or for 12 months maximum

PAZOPANIB

vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.

Active Comparator: Vinblastine and Methotrexate: Active Comparator: Vinblastine and Methotrexate vinblastine 5 mg / m², methotrexate 30 mg / m (J1, J8, J15, J21, 6 months and then J1, J15) 28 days per cycle until disease progression or for 12 months.

Vinblastine and Methotrexate

Total

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

France

Region of Enrollment

Pr Antoine Italiano, coordinating investigator

Population evaluable for efficacy included all patients who met eligibility criteria and had received at least one complete cycle or two incomplete cycles of treatment.

Percentage of Patients Remaining Alive and Progression-free at 6 Months as Per RECIST 1.1 After the Day of Randomisation (6-month Non-progression Rate).

Complete response

Partial response

Stable disease

Progression

Inevaluable for response

Percentage of Patients Remaining Alive With Best Overall Response as Per RECIST v1.1.

Spots Global Cancer Trial Database for active comparator: vinblastine and methotrexate