Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors
Condition: Desmoplastic Small Round Cell Tumor; Ewing Sarcoma of Bone or Soft Tissue; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
MeSH terms: Neoplasms; Sarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Desmoplastic Small Round Cell Tumor
Intervention: vincristine; doxorubicin; cyclophosphamide; ifosfamide; etoposide; temozolomide; temsirolimus; bevacizumab; sorafenib; surgery; radiation
Intervention description: Dosage and route of administration: Infants < 12 months of age: 0.05 mg/kg IV day 1; participants ≥ 12 months of age: 1.5 mg/m^2 IV day 1 (max. dose 2 mg).; Dosage and route of administration: Infants < 1 year 2.5 mg/kg continuous infusion (CI) over 48 hours, days 1-2; participants > 1 year of age 75 mg/m^2 CI over 48 hours, days 1-2.; Dosage and route of administration: The dose and route are different in neo-adjuvant/adjuvant chemotherapy and maintenance therapy. Please see the Detailed Description for further information.; Dosage and route of administration: Infants < 1 year of age 60 mg/kg/day IV over 60 minutes days 1-5; participants > 12 months of age 1800 mg/m^2 IV over 60 minutes x 5 days, days 1-5.; Dosage and route of administration: Infants < 1 year of age 3.3 mg/kg/day IV over 60 minutes days 1-5; children > 1 year 100 mg/m^2 daily IV over 60 minutes days 1-5.; Dosage and route of administration: Temozolomide 100 mg/m^2 PO once daily, days 1-5.; Dosage and route of administration: Temsirolimus 35 mg/m^2 IV once day 1 and day 8.; Dosage and route of administration: Bevacizumab 15 mg/kg IV on day 1 every 3 weeks.; Dosage and route of administration: 90 mg/m^2/dose PO BID; If participant meets the criteria, they will have surgical resection of their tumor.; If the participant meets the criteria, participants will receive radiation therapy. Chemotherapy will continue during radiation.
Intervention MeSH terms: Cyclophosphamide; Temozolomide; Ifosfamide; Bevacizumab; Doxorubicin; Etoposide; Vincristine; Sorafenib; Temsirolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Maximum age: 25 Years
Healthy volunteers: No

Summary:

      This protocol will study treatment for Ewing sarcoma family of tumors (ESFT) and desmoplastic
      small round cell tumor (DSRCT). Participants with ESFT will be divided into two treatment
      groups, A or B, based on tumor characteristics.

      Group A (standard risk) participants have tumor that is not in the pelvis, has not spread to
      other parts of the body, and are less than 14 years of age. Because previous clinical trials
      have shown that standard treatment is very effective for children whose tumors have these
      characteristics, these participants will receive standard treatment.

      Group B (high risk) participants are 14 years of age or older or have tumor in the pelvis, or
      the tumor has spread to other parts of the body. Participants with DSRCT in the abdomen
      and/or pelvis or with tumor that cannot be removed by surgery alone or has spread to other
      parts of the body will be included in Group B. Participants in this group are considered high
      risk because there is a greater chance of tumor recurring following standard treatments
      currently in use.

      All participants will be followed and evaluated for 10 years following completion of therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Group A participants must be <14 years of age at time of diagnosis of histologically
             proven non-pelvic localized Ewing sarcoma family of tumor (ESFT) involving the bone or
             soft tissue.

          -  Group B participants must have newly diagnosed of histologically proven ESFT involving
             the bone or soft tissue and at least one of the following: metastatic disease (must be
             biopsy proven), or pelvic primary, or ≥14 years of age at the time of diagnosis.

          -  OR Group B participants must be newly diagnosed with intra-abdominal, unresectable or
             metastatic desmoplastic small round cell tumor. Metastatic site must be biopsy proven.

          -  Age must be ≤25 years.

          -  Adequate bone marrow function defined as a peripheral absolute neutrophil count (ANC)
             ≥750/m^3 and platelet count ≥75,000/m^3 (no transfusion within 7 days of study
             enrollment). Patients with Ewing sarcoma metastatic to the bone marrow are not
             required to meet bone marrow criteria for study eligibility and are not evaluable for
             hematologic toxicity.

          -  Must have adequate renal function based on age.

          -  Must not have had prior chemotherapy or radiation therapy. Emergent radiotherapy to
             preserve vital organ function is permitted. Participants who receive emergent
             radiation will not be eligible for window therapy.

          -  Must have adequate hepatic function defined as total bilirubin ≤3.0 mg/dL.

          -  Must have adequate cardiac function defined as shortening fraction ≥28%.

          -  Females of childbearing potential and males able to father a child must be willing to
             practice acceptable methods of birth control to prevent pregnancy.

          -  Additional criteria for Group B participants who will receive upfront window therapy
             (does not apply to participants who opt out of window therapy):

               -  Cytochrome P450 CYP3A4 active agents: Must not be taking any of the following
                  potent CYP3A4 inducers or inhibitors within 1 week prior to study entry: azole
                  antifungals (such as fluconazole, voriconazole, itraconazole, ketoconazole),
                  rifampin, phenytoin, phenobarbitol, carbamazepine, grapefruit juice and St.
                  John's wort.

               -  Must have measurable disease.

               -  Must not have received emergent radiation therapy.

               -  Serum triglyceride level ≤ 300 mg/dL and serum cholesterol ≤ 300 mg/dL.

               -  Random or fasting glucose within the upper limits of normal for age. If random
                  glucose is elevated, fasting glucose must be within normal range.

               -  SGOT (AST) and SGPT (ALT) ≤3.0 x upper limit of normal for age.

        Exclusion Criteria:

          -  Participant is pregnant or breastfeeding.

          -  Inability or unwillingness of research participant or legal guardian/representative to
             give written informed consent.

          -  Participant has a prior history of malignancy, with the exception of non-melanoma skin
             cancer. Participants with history of skin cancer must have 5 years elapse since that
             diagnosis, be in remission, and must not have received chemotherapy, immunotherapy, or
             radiation therapy.