Nationwide Children’s, Dana Farber & University of Utah Pursue Future Cure to Ewing Sarcoma

Sep 2, 2019 | Cancer, Ewing Sarcoma, Oncology, Pediatrics

Nationwide Children’s, Dana Farber & University of Utah Pursue Future Cure to Ewing-Sarcoma

Through the National Cancer Institute’s Moonshot Cancer Initiative, the federal government is funding multimillion-dollar moonshot grants (U54) to researchers dedicated to understanding Ewing sarcoma and developing new therapeutic targets for the cancer. The grants were awarded to investigators at the University of Utah, Dana-Farber Cancer Institute and the Abigail Wexner Research Institute at Nationwide Children’s Hospital. These researchers are on a mission to unravel the mysteries of how Ewing sarcoma forms, how it spreads, and how it can be defeated.

Gearing up to Understand Ewing sarcoma in Ohio

Abbie Roth, managing editor of Pediatrics Nationwide and Science Communications at Nationwide Children’s Hospital, contributed to The Columbus Dispatch on reports that this race to cure Ewing sarcoma takes on new meaning when one considers the implications of children afflicted with the cancer. The prognosis is not good. Although the solid tumor cancer typically develops in the bones of the arms and legs, reports Ms. Roth, the cancer is known to start spreading through a child’s body. With a 70% survival rate with localized Ewing sarcoma, once it starts spreading the survival rate of five years after diagnosis is only 30%.

Ewing Sarcoma Elements

Ms. Roth summarizes the elements including 1) Ewing sarcoma develops differently from other common childhood cancers; 2) it is driven by a transcription factor called EWS/FLI (note transcription factors determine which genes—portions of a cell’s DNA, or stored genetic material—get translated into RNA)—the genetic material that guides the formation of proteins; 3) EWS/FLI transcription factor changes the genes being expressed in the cell; 4) resulting in an accumulation of cancer causing proteins leading to Ewing sarcoma tumor formations; 5) other features may also go on to develop the cancer.

Recent Study Results

Researchers recently described how GGAA-microsatellites (repetitive DNA) contribute to the formation of Ewing sarcoma. The location of a GGAA-microsatellite “in a sweet spot” length can drive the formation of Ewing sarcoma.

Ewing Sarcoma Current Treatments

Current treatments include chemotherapy, radiation therapy, surgery and stem cell transplant. Targeted therapy and immunotherapy are being studied. 

Incidence

Ewing sarcomas represent 16% of primary bone sarcomas. In the United States, they are most common in the second decade of life, with a rate of 0.3 cases per mission in children under 3 years of age, and as high as 4.6 cases per million in adolescents aged 15-19 years. Internationally, the annual incidence rate averages less than 2 cases per million children. In the UK, an average of six children per year are diagnosed.

Phase 3 Clinical Trials

TrialSite News reviewed present Phase III clinical trials involving Ewing sarcoma. We found five (5) Phase III studies including:

Sponsor—Italian Sarcoma Group. The study, a controlled, randomized phase III study, with the intent of optimizing the treatment of not metastatic Ewing Sarcoma. The patients will be randomized into 2 arms: standard treatment vs intensive treatment. Both arms will receive an induction treatment followed by surgery (wherever is possible) and/or radiotherapy. The maintenance treatment will be different on the basis of the response to the induction treatment (good or poor).  This study runs until 2021. The Italian study is led by principal investigator Stefano Ferrari, MD, Italian Sarcoma Group.

Sponsor—Gradalis Inc.  The study is a multicenter, 1:1 randomized Phase III study of intradermal autologous Vigil immunotherapy (1.0 x 10e6 cells/injection; minimum of 4 to a maximum of 12 administrations) in combination with irinotecan and temozolomide in subjects with metastatic Ewing’s sarcoma Family of Tumors (ESFT) refractory/intolerant or recurrent to 1 prior line of chemotherapy. Participants undergoing a standard surgical procedure (e.g., tumor biopsy or palliative resection) may have tumor tissue harvested for manufacture of the investigational product, Vigil. The study runs until 2022 and will include 114 participants.  Dozens of U.S. clinical investigational sites are participating and the sponsor’s lead investigator is Luisa Manning, MD.

Sponsor—Children’s Oncology Group.  The study is a randomized phase III trial studying combination chemotherapy to see how well it works compared to combination chemotherapy with topotecan hydrochloride in treating patients with extracranial Ewing sarcoma that has not spread from the primary site to other places in the body. Drugs used in chemotherapy, such as vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, etoposide, and topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether combination chemotherapy is more effective with topotecan hydrochloride in treating Ewing sarcoma. The study runs till the end of 2019 and is led by Children’s Oncology Group principal investigator Patrick J. Leavey.

Sponsor—the National Cancer Institute. The NCI leads this randomized phase III trial and studies how well combination chemotherapy with or without ganitumab (Amgen) works in treating patients with newly diagnosed Ewing sarcoma that has spread to other parts of the body. Immunotherapy with monoclonal antibodies, such as ganitumab, may help the body’s immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether combination chemotherapy is more effective with or without ganitumab in treating patients with newly diagnosed Ewing sarcoma. The study lasts till 2020. The principal investigator is Steven G. DuBois, Children’s Oncology Group.

Sponsor– Hôpitaux de Paris. The purpose of this study is to determine the efficacy of a temporary ovarian suppression obtained by administration of a gonadotropin releasing hormone agonist during alkylating agents containing chemotherapy on ovarian reserve assessed by Anti-Müllerian hormone (AMH) serum levels in adolescents and young women with cancer. The study ends 2021 and includes Cecile Thomas-Teinturier, MDAP-HP, Bicêtre Hospital

Call to Action: Interested in monitoring Ewing sarcoma research? We recommend following the Moonshot initiatives as well as some of the clinical trials ongoing.

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