Cyclophosphamide, Doxorubicin, Vincristine w/ Irinotecan and Temozolomide in Ewings Sarcoma
Condition: Bone Cancer; Ewing's Sarcoma
MeSH terms: Sarcoma; Sarcoma, Ewing; Bone Neoplasms
Intervention: Irinotecan; Vincristine; Temozolomide; Doxorubicin; Cytoxan; Pegfilgrastim
Intervention description: 50 mg/m2/day x 5 days; 2 mg/m2 to a maximum of 2 mg; 100 mg/m2/day x 5 days followed by 2 weeks treatment-free; Starting dose 75 mg/m2 to a maximum of 450mg/m2; 1200 mg/m2; 6 mg subcutaneous within 24 to 48 hours after each Regimen A cycle
Intervention MeSH terms: Cyclophosphamide; Temozolomide; Doxorubicin; Irinotecan; Vincristine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 13 Years
Healthy volunteers: No

Summary:

      The outcome of patients with metastatic Ewings Sarcoma is poor with current standard of care
      chemotherapy, with less than 30% survival. Based on recent encouraging pediatric literature
      we have designed this trial to improve the outcome of patients with metastatic Ewings sarcoma
      using Irinotecan and Temozolomide in addition to standard chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed diagnosis of metastatic Ewing's sarcoma.

          -  Patients must have measurable disease defined as lesions that can be measured by
             medical imaging techniques such as CT or MRI. Ascites, pleural fluid, bone marrow
             disease, lesions seen on scan will not be considered measurable.

          -  Patients must have metastatic disease.

          -  Age 13 years or older

          -  Life expectancy of at least 3 months.

          -  ECOG performance status of <= 3.

          -  Normal hepatic function (Direct bilirubin <1.5mg/dl, SGOT or SGPT <3x upper limit of
             normal).

          -  Left Ventricular Ejection fraction of at least 50%.

          -  Adequate renal function: Creatinine clearance >= 50 ml/min or Serum creatinine < 1.5 x
             ULN for age.

          -  Adequate bone marrow reserve (defined as an absolute peripheral granulocyte count of
             >=1500/mm3, platelet count of >=75,000/mm3); unless bone marrow infiltrated with
             metastatic Ewing's sarcoma; ANC >= 500 and Platelet >= 50,000 mm3.

          -  Ability to understand and willing to sign a written informed consent document.

          -  Patients of childbearing potential must agree to use an effective method of
             contraception.

        Exclusion Criteria:

          -  No prior chemotherapy for Ewing's sarcoma; No prior doxorubicin, temozolomide or
             irinotecan.

          -  Known hypersensitivity to any of the components of the protocol drugs.

          -  Clinically significant unrelated systemic illness (such as serious infections
             requiring active systemic intravenous antibiotic therapy; cardiovascular disease
             [congestive heart failure, recent myocardial infarction, unstable angina, inadequately
             controlled hypertension].

          -  No prior history of chronic diarrhea, bowel obstruction, Crohn's disease or ulcerative
             colitis.

          -  Pregnant or nursing woman are not included in the study.

          -  HIV-positive patients will be excluded from the study due to risk of infection or
             other serious side effects.

          -  Other medical, psychiatric or social condition incompatible with study treatment.