Vincristine Sulfate, Topotecan Hydrochloride, and Cyclophosphamide With or Without Bevacizumab in Treating Young Patients With Refractory or First Recurrent Extracranial Ewing Sarcoma
Condition: Ewing Sarcoma of Bone; Extraosseous Ewing Sarcoma; Peripheral Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
MeSH terms: Sarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Recurrence
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial study has a 6-patient feasibility portion studying the tolerability of
      chemotherapy with vincristine sulfate together with topotecan hydrochloride,
      cyclophosphamide, and bevacizumab in treating young patients with refractory or first
      recurrent extracranial Ewing's sarcoma. If the therapy is considered tolerable, this
      feasibility run-in will be followed by a randomized phase II portion studying giving
      vincristine sulfate together with topotecan hydrochloride, and cyclophosphamide to see how
      well it works compared with giving vincristine sulfate together with topotecan hydrochloride,
      cyclophosphamide, and bevacizumab in treating young patients with refractory or first
      recurrent extracranial Ewing's sarcoma. Drugs used in chemotherapy, such as vincristine
      sulfate, topotecan hydrochloride, and cyclophosphamide, work in different ways to stop the
      growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some
      block the ability of tumor cells to grow and spread. Others find tumor cells and help kill
      them or carry tumor-killing substances to them. Bevacizumab may also stop tumor growth by
      blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab
      may kill more tumor cells.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To determine the feasibility of administering bevacizumab in combination with vincristine
      (vincristine sulfate), topotecan hydrochloride, and cyclophosphamide (VTC) to younger
      patients with refractory or first recurrent Ewing sarcoma.

      II. To compare the progression-free survival of patients treated with VTC with bevacizumab vs
      VTC without bevacizumab.

      SECONDARY OBJECTIVES:

      I. To estimate the response rate to 2 cycles of VTC compared to 2 cycles of VTC/bevacizumab.

      II. To evaluate biological markers as related to prognosis and specifically related to
      angiogenesis by encouraging concurrent enrollment on the Ewing sarcoma banking studies
      (COG-AEWS02B1 and/or COG-AEWS07B1) and ancillary correlative endothelial cell, surrogate
      marker, and angiogenic gene studies.

      OUTLINE: This is a single therapy feasibility study followed by a randomized controlled
      portion. Patients are stratified according to time to disease recurrence (< 2 years vs >= 2
      years).

      ARM I (Feasibility assessment of VTCB): Patients receive bevacizumab intravenously (IV) over
      30-90 minutes on day 1, vincristine sulfate IV on days 1, 8, and 15, and topotecan
      hydrochloride IV over 30 minutes and cyclophosphamide IV over 60 minutes on days 1-5.
      Treatment repeats every 21 days (except during weeks 14, 15 [course 5], 17, 18 [course 6],
      26, 27 [course 9], 29, and 30 [course 10] when no chemotherapy is given) for up to 12 courses
      in the absence of disease progression or unacceptable toxicity.

      ARM II (VTCB): Patients receive bevacizumab, vincristine sulfate, topotecan hydrochloride,
      and cyclophosphamide as in Arm I.

      ARM III (VTC): Patients receive vincristine sulfate, topotecan hydrochloride, and
      cyclophosphamide as in arm I.

      After completion of study therapy, patients are followed periodically.
    

Intervention name(s): topotecan hydrochloride; vincristine sulfate; cyclophosphamide; bevacizumab
Intervention type(s): Drug; Drug; Drug; Biological
Intervention description(s): Given IV; Given IV; Given IV; Given IV
Other intervention name(s): hycamptamine; Hycamtin; SKF S-104864-A; TOPO; leurocristine sulfate; VCR; Vincasar PFS; CPM; CTX; Cytoxan; Endoxan; Endoxana; anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; Avastin; rhuMAb VEGF
Intervention MeSH terms: Cyclophosphamide; Bevacizumab; Vincristine; Topotecan; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment