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Biologically-Adapted, Dose-Escalated Radiotherapy for the Treatment of Ewing Sarcoma, BEAR Trial
Trial Status: active
This clinical trial evaluates the effect of radiotherapy doses based on tumor size and tumor-specific characteristics (biologically-adapted) in treating patients with Ewing sarcoma. Radiotherapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Conventional radiotherapy uses minimal imaging support to determine the positioning of radiotherapy. Hypofractionated radiotherapy delivers higher doses of radiotherapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Dose-escalated radiotherapy uses doses that are higher than those used in conventional radiotherapy. Larger tumor sizes and other tumor-specific characteristics have been shown to be related to poorer outcomes. In addition, after dose-escalated radiotherapy, patients with larger tumors have demonstrated improved control of the disease at the primary tumor site. Giving biologically-adapted, dose-escalated radiotherapy may reduce the return of the cancer at the primary tumor site in patients with Ewing sarcoma with large tumors and other unfavorable characteristics. This clinical trial also evaluates the role of biomarkers in patients with Ewing sarcoma. Studying samples of blood and tumor tissue from patients with Ewing sarcoma in the laboratory may help doctors learn more about predicting the amount of disease and the likelihood of the cancer coming back.
Inclusion Criteria
Histological confirmation of Ewing sarcoma, including both skeletal and extra-skeletal primary tumors. Patients with “Ewing-like” sarcoma may be eligible if patients are planned to be treated per Ewing treatment paradigms, as defined in this clinical trial
Patients of age ≥ 2 years are eligible for the study
Lansky or Karnofsky performance status ≥ 70
Ability to provide written informed consent and complete questionnaire(s) by themselves or with assistance
Willing to provide blood samples for correlative research purposes
Willing to provide biopsy sample to run Mayo Complete Solid Tumor Panel if tumor size is ≥ 8 cm
Exclusion Criteria
Prior chemotherapy or radiotherapy that, in the opinion of the treating medical oncologist or radiation oncologist, is considered to interfere with the current treatment or measurement of outcomes
Receiving any investigational agent which would be considered as a treatment for the primary neoplasm that is considered by the investigator to interfere with the current treatment or measurement of outcomes
* Note: Co-enrollment on another clinical trial is allowed per the treating radiation oncologist’s discretion
Other active malignancy ≤ 1 year prior to registration that is considered by the investigator to interfere with the current treatment or measurement of outcomes
Patients that have severe co-morbid systemic illness or other disease which would interfere significantly with the current treatment or measurement of outcomes
Patients that have active uncontrolled systemic infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric illness or social situation that would limit study adherence
Any of the following:
* Pregnant patients
* Nursing patients
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07188532.
I. Demonstrate a reduction in local failure for patients with large tumors (≥ 8cm) at diagnosis, unfavorable tumor biology, and treated with definitive radiotherapy compared to the historical control of 14.3%.
SECONDARY OBJECTIVES:
I. Report targeted, late grade 3 (G3)+ toxicity at 1 year after completion of radiotherapy for large tumors.
II. To demonstrate non-inferiority of targeted, acute G3+ toxicity of selective dose-escalated and accelerated radiotherapy for Ewing sarcoma compared to historical controls.
III. Report event-free survival (EFS), local control, overall survival (OS) at 2 years after completion of local therapy for large tumors.
CORRELATIVE OBJECTIVES:
I. Report leukopenia rates and compare between pre-defined subgroups.
II. Evaluate chemotherapy delay secondary to local therapy.
III. Explore the predictive and prognostic role of ctDNA in Ewing sarcoma.
IV. Study the predictive and prognostic role of tumor-derived extracellular vesicles (tdEVs) in Ewing sarcoma.
V. Apply ctDNA approaches using fragment size in the setting of Ewing sarcoma.
VI. Investigate the predictive role of positron emission tomography (PET)/computed tomography (CT) and/or magnetic resonance imaging (MRI) in assessing treatment response and apply novel radiomic techniques to maximize this predictive power.
VII. Assess acute G3+ toxicity for patients receiving preoperative or postoperative radiotherapy for the purposes of local control.
VIII. Assess patient-reported outcomes after local therapy, per the Pediatric Quality of Life (PEDSQL) 4.0 generic core instrument or Patient Reported Outcomes Measurement Information System (PROMIS)-29.
IX. Report EFS, local control, OS at 2 year after completion of any local therapy.
OUTLINE: Patients are assigned to 1 of 3 cohorts based on treatment and the size of the tumor at the time of radiotherapy.
COHORT A: Patients with specific high-risk characteristics are assigned to Group 1 and patients with no specific high-risk characteristics are assigned to Group 2:
GROUP 1: Patients may receive standard of care (SOC) chemotherapy every 2 weeks for at least 3 cycles prior to radiotherapy. Patients then undergo hypofractionated or conventional dose-escalated radiotherapy daily, excluding weekends and holidays, for 25-36 treatment fractions in the absence of disease progression or unacceptable toxicity. Patients may also receive consolidation chemotherapy after completion of radiotherapy and/or surgical resection.
GROUP 2: Patients may receive SOC chemotherapy every 2 weeks for at least 3 cycles prior to radiotherapy. Patients then undergo hypofractionated or conventional standard dose radiotherapy daily, excluding weekends and holidays, for 25-31 treatment fractions in the absence of disease progression or unacceptable toxicity. Patients may also receive consolidation chemotherapy after completion of radiotherapy and/or surgical resection.
COHORT B: Patients may receive SOC chemotherapy every 2 weeks for at least 3 cycles prior to radiotherapy. Patients with tumor size < 8cm at diagnosis undergo definitive radiotherapy or surgical resection. Patients may also receive consolidation chemotherapy after completion of definitive radiotherapy or surgical resection.
COHORT C: Patients may receive SOC chemotherapy every 2 weeks for at least 3 cycles prior to radiotherapy. Patients undergo radiotherapy before or after undergoing definitive surgical resection. Patients may also receive consolidation chemotherapy after completion of definitive radiotherapy and surgical resection.
Patients also undergo blood sample collection throughout the study. Additionally, patients may also undergo CT, PET/CT, and MRI with or without CT throughout the study at treating clinician's discretion.
After completion of study treatment, patients are followed up at 1 month and medical records are reviewed for up to 5 years. Patients in Cohort A are also followed at 3, 6, 12 and 24 months after radiotherapy and/or surgical resection. Additionally, patients in Cohort C are followed up at 3 months.
