Sirolimus Versus Sirolimus Plus Prednisolone for Kaposiform Hemangioendothelioma
Condition: Kaposiform Hemangioendothelioma; Kasabach Merritt Phenomenon
MeSH terms: Sarcoma, Kaposi; Hemangioendothelioma; Kasabach-Merritt Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm that occurs predominantly
      in infancy or early childhood. KHE has a nearly equal sex ratio. The annual incidence of KHE
      has been estimated at 0.071 per 100,000 children. KHE presents with intermediate-malignant
      and locally aggressive characteristics but without distant metastases.

      This pilot trial studies sirolimus versus sirolimus plus pednisolone in treating patients
      diagnosed with kaposiform hemangioendothelioma (KHE) and Kasabach-Merritt phenomemon (KMP)
      that cannot be removed by surgery. The purpose of this study is to compare the efficacy and
      safety of orally administered sirolimus versus sirolimus plus pednisolone in the treatment of
      KHE associated with KMP.
    

Detailed description: 
      Kasabach-Merritt phenomemon (KMP) is a profound thrombocytopenia resulting from intralesional
      platelet trapping. It is now clear that KMP occurs with KHE and tufted angioma, not with
      infantile or congenital hemangiomas. KMP is typically associated with more aggressive lesions
      and poorer outcomes. Clinically significant KMP is a severe thrombocytopenia, generally below
      30× 109/L. Severe thrombocytopenia may indicate a severer tumor, a progressive tumor,
      partially or totally insensitive to therapy. In addition to severe, persistent
      thrombocytopenia characteristic of KMP, patients often manifest elevated D-dimer and low
      fibrinogen. Coagulopathy in addition to thrombocytopenia is associated with more aggressive
      presentations and may indicate current infection or inflammation. Additionally, KMP may be
      complicated by severe anemia due to blood sequestration and intra-lesional hemorrhaging. KHE
      with KMP have notably high morbidity and mortality rates, resulting predominantly from rapid
      tumor growth and infiltration, compression or destruction of vital structures, and
      hemodynamic instability.

      Consensus treatment guidelines from a multidisciplinary expert panel were published in 2013.
      Medical treatments with corticosteroids and/or vincristine have been recommended for the
      management of KHE. However, first-line treatment with corticosteroids is successful in only
      10-27% of all cases, and treatment with vincristine is successful in 60-70% of patients.
      Moreover, vincristine monotherapy has not been confirmed to provide significant benefits in
      critically ill patients.

      Sirolimus (also known as rapamycin) is an inhibitor of the mammalian target of rapamycin
      (mTOR). In recent studies, sirolimus was shown to be effective in patients with complex
      vascular anomalies, including KHE. Our multicenter, retrospective study demonstrated that
      oral sirolimus is an effective and safe option for the treatment of progressive KHE.
      Additionally, our data emphasized that the KHE treatment regimen should be tailored to
      individual patients and guided by specific clinical circumstances. In cases of severe
      Kasabach-Merritt phenomenon (KMP), sirolimus in combination with the short-term
      administration of prednisolone is recommended for controlling life-threatening conditions.
    

Intervention name(s): Sirolimus; Prednisolone
Intervention type(s): Drug; Drug
Intervention description(s): Oral administration; Oral administered with sirolimus
Other intervention name(s): Rapamycin
Intervention MeSH terms: Sirolimus; Prednisolone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Kaposiform Hemangioendothelioma; Kasabach Merritt Phenomenon; Sirolimus; Prednisolone