Cabozantinib With Topotecan-Cyclophosphamide
Condition: Relapsed Ewing Sarcoma; Refractory Ewing Sarcoma; Relapsed Osteosarcoma; Refractory Osteosarcoma
MeSH terms: Sarcoma; Osteosarcoma; Sarcoma, Ewing
Study type: Interventional
Phase: Phase 1

Summary: 
      This research study is a clinical trial of a new combination of drugs as a possible treatment
      for relapsed/refractory Ewing sarcoma and/or osteosarcoma.

        -  The names of the drugs are:

             -  Cabozantinib

             -  Topotecan

             -  Cyclophosphamide

        -  The names of the non-investigational supportive care drugs are:

             -  Filgrastim, pegfilgrastim, or a related growth factor.
    

Detailed description: 
      This is a prospective, open-label, single arm, phase 1 clinical trial. A single cohort of
      patients with relapsed or refractory Ewing sarcoma or osteosarcoma will be enrolled and
      treated in a 3+3 design with a combination of cabozantinib, topotecan and cyclophosphamide.

      The research study procedures include screening for eligibility and study treatment including
      medical tests and follow up visits.

        -  The names of the drugs are:

             -  Cabozantinib

             -  Topotecan

             -  Cyclophosphamide

        -  The names of the non-investigational supportive care drugs are:

             -  Filgrastim, pegfilgrastim, or a related growth factor.

      It is expected that up to 16 people will take part in this research study.

      This research study is a Phase I clinical trial, which tests the safety of an investigational
      drug combination and also tries to define the appropriate doses of the drugs to use for
      further studies. "Investigational" means that the drug combination is being studied.

      The FDA (the U.S. Food and Drug Administration) has approved all medications included in this
      trial as a treatment for multiple types of cancers.

      The combination of topotecan and cyclophosphamide has been used for treatment of this
      population. Cabozantinib has been used alone for treatment of Ewing sarcoma and osteosarcoma
      and shown to have an effect in some patients. This is the first time that cabozantinib will
      be studied in combination with topotecan and cyclophosphamide.
    

Intervention name(s): Cabozantinib; Topotecan; Cyclophosphamide; Myeloid growth factor
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): PO (dose and schedule based upon dose level and nomogram); IV, over 30 minutes (schedule based upon dose level); IV, over 30 minutes (schedule based upon dose level); subcutaneous filgrastim (daily until ANC ≥ 1,500/mm3 after nadir) or pegfilgrastim (once) must be given, with choice of agent per institutional standard or treating physician preference, starting on day 5, 6, 7 or 8 (depending upon chemotherapy timing)
Other intervention name(s): COMETRIQ™; Hycamtin®; Neosar®; Cytoxan®; Filgrastim; Pegfilgrastim
Intervention MeSH terms: Cyclophosphamide; Topotecan; Mitogens
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Relapsed Ewing Sarcoma; Refractory Ewing Sarcoma; Relapsed Osteosarcoma; Refractory Osteosarcoma