Doxorubicin Eluting Intra-arterial Embolization for Aggressive Desmoid Fibromatosis
Condition: Desmoid; Desmoid Fibromatosis of Skin; Desmoid Neoplasm of Chest Wall; Desmoid Tumor Caused by Somatic Mutation; Aggressive Fibromatoses; Fibromatosis Desmoid; Desmoid Fibromatosis
MeSH terms: Fibromatosis, Aggressive; Fibroma; Aggression
Study type: Interventional
Phase: Phase 2

Summary: 
      In this study Drug-eluting microbeads (DEB) loaded with Doxorubicin will be delivered into
      the target Desmoid Fibromatoses (DF) tissue via selective arterial embolization by
      angiographic technique. The objective of the study is to demonstrate the safety and efficacy
      of this treatment.
    

Detailed description: 
      Desmoid Fibromatoses (DF) are locally aggressive lesions associated with substantial
      morbidity and potentially mortality, due to invasion of adjacent neurovascular structures and
      vital organs. They have no potential for metastasis. Histologically, they are characterised
      by mature fibroblasts within a matrix of abundant fibrous stroma. While 5-15% of cases are
      seen in patients with Familial Adenomatous Polyposis (FAP) syndrome, the vast majority arise
      sporadically.

      The etiology of Desmoids remains poorly understood and the therapeutic approaches in their
      management remain very diverse. For resectable lesions, surgery is recommended but reported
      cure rates range broadly from 12-80%. Systemic treatments range from non-steroidal
      anti-inflammatories and anti-estrogenic therapy to targeted tyrosine kinase inhibitors and
      cytotoxic chemotherapy, most commonly methotrexate, vinblastine and doxorubicin.

      Doxorubicin is an anthracycline with demonstrated efficacy in treating desmoids at systemic
      IV doses of 50- 75mg/m2 over 3-4 week cycles. Extended use is limited by dose - dependent
      cardiotoxicity which can be seen in up to 36% of patients receiving doses in excess of
      550mg/m2. Delayed cardiotoxicity is particularly common and less predictable among pediatric
      cancer survivors.

      Selective trans-arterial chemo-embolization (TACE) is a method to achieve high tissue drug
      concentration with minimal systemic toxicity. Historically, this has been achieved by mixing
      doxorubicin with embolic agents such as lipiodol or gelatin sponge in the treatment of
      hepatocellular carcinoma (HCC).

      Drug-eluting microbeads (DEB) ionically loaded with doxorubicin have shown sustained release
      in TACE target tissues with substantially lower serum drug concentrations when compared to
      lipiodol TACE.

      The present study utilizes DEB's loaded with Doxorubicin delivered into the target DF tissue
      via selective arterial embolization by angiographic technique. This study follows a
      successful feasibility study.
    

Intervention name(s): Drug Eluting Bead Embolization (DEB) for Desmoid Fibromatosis
Intervention type(s): Procedure
Intervention description(s): Delivery of Doxorubicin selectively into Desmoid Fibromatosis utilizing its vascular supply as a conduit, and ionic loading the doxorubicin onto embolized particles as the drug delivery vehicle.
Maximal dose is 75 mg/m2 and at least 50 mg. The bead size is 75-300 Mµ in a 2 CC syringe.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention model description: All patients
Masking: None (Open Label)
Primary purpose: Treatment