ESFT13: Therapeutic Trial for Patients with Ewing Sarcoma Family of Tumors and Desmoplastic Small Round Cell Tumors

Combination Chemotherapy with or without Sorafenib Tosylate and Bevacizumab in Treating Patients with Ewing Sarcoma or Desmoplastic Small Round Cell Tumors

Category:

Solid Tumor

Diseases Treated:

Ewing Sarcoma Family of Tumors and Desmoplastic Small Round Cell Tumors

Eligibility Overview:

  • Diagnosis of Ewing sarcoma and/or desmoplastic small round cell tumor (DSRCT)
  • Less than 25 years of age
  • Has not received previous treatment with radiation therapy or chemotherapy. Emergent radiation therapy to preserve vital organ function is permitted.
  1. Brief Summary

    This protocol will study treatment for Ewing sarcoma family of tumors (ESFT) and desmoplastic small round cell tumor (DSRCT).

    Primary Objective

    To estimate the response rate to 2 initial courses of temsirolimus, temozolomide and irinotecan in previously untreated patients with high-risk Ewing sarcoma family of tumors (ESFT)

    Trial Outline

    Participants with ESFT will be divided into 2 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.

    Study Arms

    Active Comparator: Group A (Standard Risk)

    Participants will receive vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide. Doxorubicin will be omitted following a total cumulative dose of 375 mg/m^2. Depending on the size and location of the participants’ tumor, they will have surgery alone, radiation alone, or surgery followed by radiation. Local control measures (surgery and/or radiation therapy) will be instituted after 6 courses of chemotherapy. Total duration of treatment is approximately 29 weeks.

    Interventions

    • Drugs: Vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide
    • Procedure: Surgery
    • Radiation: Radiation

    Active Comparator: Group B (High Risk)

    Participants will receive vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, irinotecan, temozolomide, temsirolimus, bevacizumab, and sorafenib. Depending on the size and location of the participant's tumor, they will have surgery alone, radiation alone or surgery followed by radiation.

    Interventions

    • Drugs: Doxorubicin, cyclophosphamide, ifosfamide, etoposide, temozolomide, temsirolimus, bevacizumab, sorafenib
    • Procedure: Surgery
    • Radiation: Radiation

    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 tumors (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.

    Study Design

    • Allocation: Non-Randomized
    • Endpoint Classification: Efficacy Study
    • Intervention Model: Parallel Assignment
    • Masking: Open Label
    • Primary Purpose: Treatment
  2. About this clinical trial

    ESFT13 is a Phase II study, which is being conducted only at St. Jude Children’s Research Hospital. In this clinical trial, researchers are testing an experimental chemotherapy combination that may help children and adolescents with newly diagnosed high-risk Ewing sarcoma and desmoplastic small round cell tumors (DSRCTs).

    Ewing sarcoma is a cancer that grows in the bones or in the soft tissue around bones – often occurring in the legs, pelvis, ribs, arms or spine. DSRCTs are a type of cancer that can occur anywhere in the body, but is usually found in the belly. Tumors are comprised of small, round cancer cells and are surrounded by scar-like tissue

    Treatment

    There are three parts to this study:

    • Screening – Tests and procedures will be done to find out if this study is a good option for your child.
    • Treatment – The stage of Ewing sarcoma or whether your child has DSRCT will determine the treatment your child will receive. (See details in chart below.)
    • Follow-up – There will be regular follow-up visits for 10 years after.
    If your child has ... Then your child will receive ... Also, if your child ...
    Ewing sarcoma that has a low risk of tumors coming back after treatment and/or desmoplastic small round cell tumor Standard treatment - Chemotherapy including vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide, followed by surgery and/or radiation to the tumor site.

     

    Has surgery to remove the tumor and if there is a large amount of living tumor cells present in the removed tumor, your child will be eligible to receive proton beam radiation therapy to reduce the risk of the cancer coming back.
    Ewing sarcoma that has a greater chance of tumors coming back after treatment (including tumors that have spread to other parts of the body, a primary tumor forming in the pelvis and if your child is greater than 14 years old) and/or desmoplastic small round cell tumor Experimental treatment + standard treatment - Two cycles of an experimental chemotherapy combination (irinotecan/temozolomide/temsirolimus) given before standard treatment (chemotherapy including vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide and etoposide, followed by surgery and/or radiation to the tumor site) Has a good response to the experimental therapy, he or she will receive the experimental therapy during standard therapy. After surgery and/or radiation to the tumor site, your child will receive a different experimental chemotherapy combination (maintenance therapy using bevacizumab, cyclophosphamide and sorafenib) to keep the cancer from coming back.

    Eligibility overview

    • Diagnosis of Ewing sarcoma and/or desmoplastic small round cell tumors (DSRCT)
    • Less than 25 years of age
    • Has not received previous treatment with radiation therapy or chemotherapy. Emergent radiation therapy to preserve vital organ function is permitted.

    Contact

    Sara M. Federico, MD

    St. Jude Children’s Research Hospital
    262 Danny Thomas Place
    Memphis, TN 38105  USA
    Voice: 1-888-226-4343 or 901-595-4055
    24-Hour Emergency Access Pager: 1-800-349-4334

    Referring or consulting clinicians only: protocolinfo@stjude.org
    For all other inquiries about St. Jude Children's Research Hospital studies: referralinfo@stjude.org

    The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.

  3. ESFT13  Quick View
    Sponsor  St. Jude Children’s Research Hospital
    Collaborators University of Tennessee Health Science Center, University of Florida and Nemours Children’s Clinic
    ClinicalTrials.gov identifier  NCT01946529
    Trial start date November 2013
    Estimated enrollment 47
    Study type Interventional
    Study phase Phase 2
    Conditions
    • 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
    Ages Up to 25 years
    Principal investigator Sara Federico, MD
    Study site St. Jude Children's Research Hospital
    For a consultation or to discuss ESFT13 St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org