Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors

Study Overview
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Brief Summary
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This research study is studying stereotactic body radiotherapy (SBRT) as a possible treatment for lung relapse of Ewing sarcoma, rhabdomyosarcoma, osteosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, Wilms tumor or other primary renal tumor (including clear cell and rhabdoid). SBRT is a form of targeted radiotherapy that can treat very small tumors using a few large doses.

Detailed Description
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This research study is a Pilot Study, also known as a Phase I-II study, which means it is the first time investigators are examining this study intervention for patients with lung recurrence of Ewing sarcoma, rhabdomyosarcoma, osteosarcoma, nonrhabdomyosarcoma soft tissue sarcoma, Wilms tumor or other primary renal tumor (including clear cell and rhabdoid). This study tests the most appropriate dose, safety and efficacy of SBRT for the treatment of lung recurrence of these cancers in children. Standard radiotherapy is typically used to treat Ewing sarcoma and is used to treat lung recurrence. SBRT is being used to treat adults with small inoperable lung cancers; in such cases, SBRT has been shown to be effective and well-tolerated. SBRT is also used to treat bone metastases in adults and children.

Official Title
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Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors

Conditions
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Ewing Sarcoma, Rhabdomyosarcoma, Wilms Tumor, Osteosarcoma, Non-Rhabdomyosarcoma Soft Tissue Sarcoma, Nos, Renal Tumor, Rhabdoid Tumor, Clear Cell Renal Cell Carcinoma, Sarcoma, Sarcoma, Ewing, Soft Tissue Sarcoma

Intervention / Treatment
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* Radiation: Stereotactic Body Radiotherapy (SBRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Ewing sarcoma, rhabdomyosarcoma, osteosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, Wilms tumor or other primary renal tumor (including clear cell and rhabdoid) Age ≤ 21 years; Must be capable of treatment without general anesthesia Lesion size 8 mm - 3 cm Subjects who have lesions within 2 cm of central structures, will be eligible on a case by-case basis Pulmonary metastases found at relapse (does not have to be first relapse); no more than 3 lesions per hemi-thorax will be treated but other lesions in the lung may be present Greater than 5 weeks from doxorubicin at the time of consent, with radiation to be initiated no less than 6 weeks from doxorubicin Informed consent/assent Life expectancy >3 months Pulmonary Function FEV1 ≥ 50% of predicted; Concurrent immunotherapy is allowed Exclusion Criteria: Prior whole-lung or hemi-thorax irradiation of greater than 12 Gy received less than 6 months prior to consent (focal radiotherapy to the thorax is not an exclusion) Lesion larger than 3 cm in diameter Patients for whom surgery would be deemed appropriate rather than radiotherapy

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Dose Level 1 [Phase I]<br>Participants with Wilms tumors or other primary renal tumors. Stereotactic Body Radiotherapy (SBRT) Dose Levels for each target lesion are three 8 Gy fractions for 24 Gy total. | Radiation: Stereotactic Body Radiotherapy (SBRT)<br> <br> |
| Experimental: Cohort 1 Dose Level 2 [Phase I]<br>Participants with Wilms tumors or other primary renal tumors. SBRT Dose Levels for each target lesion are three 10 Gy fractions for 30 Gy total. | Radiation: Stereotactic Body Radiotherapy (SBRT)<br> <br> |
| Experimental: Cohort 1 Dose Level 3 [Phase I]<br>Participants with Wilms tumors or other primary renal tumors. SBRT Dose Levels for each target lesion are three 12 Gy fractions for 36 Gy total. | Radiation: Stereotactic Body Radiotherapy (SBRT)<br> <br> |
| Experimental: Cohort 2 Dose Level 2 [Phase I]<br>Participants with Ewing sarcoma or rhabdomyosarcoma. SBRT Dose Levels for each target lesion are three 10 Gy fractions for 30 Gy total. | Radiation: Stereotactic Body Radiotherapy (SBRT)<br> <br> |
| Experimental: Cohort 2 Dose Level 3 [Phase I]<br>Participants with Ewing sarcoma or rhabdomyosarcoma.SBRT Dose Levels for each target lesion are three 12 Gy fractions for 36 Gy total. | Radiation: Stereotactic Body Radiotherapy (SBRT)<br> <br> |
| Experimental: Cohort 2 Dose Level 2 [Phase II]<br>Participants with Ewing sarcoma or rhabdomyosarcoma. SBRT Dose Levels for each target lesion are three 10 Gy fractions for 30 Gy total. | Radiation: Stereotactic Body Radiotherapy (SBRT)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicity [Phase I] | Dose Limiting Toxicities (DLT's) are toxicities experienced from start of therapy to 6 month. DLT's are assessed on the Common Terminology Criteria for Adverse Events (CTCAE) version 4. DLTs are defined as follows: Grade 2 or higher toxicities: Myelitis Esophageal fistula, perforation, hemorrhage Grade 3 or higher toxicities considered to be a direct result of therapy: Pneumonitis Pericarditis, pericardial effusion Esophageal necrosis, stenosis, ulcer Dyspnea Grade 4 toxicities: Esophagitis Pericardial tamponade Pulmonary toxicity excluding infectious pneumonia Skin toxicity Hemoptysis/pulmonary hemorrhage Grade 5 toxicities, including: Pulmonary toxicity including pneumonitis Excluding infectious pneumonia Three participants will enter the study in each cohort. If 0/3 patients experiences a DLT, this dose level will move forward to the Phase II and more participants will be enrolled. | Up to 6 months | 
| Overall Response Rate [Phase II] | Percentage of participants with response after 6 weeks. Response on treatment was considered to be Complete Response (CR) and Partial Response (PR) measured according Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. For target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate [Phase II] | Percentage of pulmonary lesions of participants with response after 6 weeks. Response on treatment was considered to be Complete Response (CR) measured according Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. For target lesions, CR is complete disappearance of all target lesions. | 6 weeks | 
| 2 Year Local Control Rate [Phase II] | Rate of local control (LC) of the index lesion after lung SBRT at 2 years. LC is defined as the absence of tumor progression within 1 cm of the primary tumor site. LC is measured by established methods. | 24 Months | 
| Percentage of Participants With 2-Year Failure-Free Survival [Phase II] | Rate of distant lung failure-free survival defined lung failure or death from any cause at two years. Lung failure defined using established methods. | 24 months | 
| Number of Participants With Grade 3 or Higher Adverse Events [Phase I and II] | Grade 3 or higher adverse events as defined by controlled terminology criteria for adverse events (CTCAE) version 4. | Up to 6 months post-treatment (6 months and 2 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Comfort Care, Ewing Sarcoma, Rhabdomyosarcoma, Wilms Tumor, Rhabdomyosarcoma of Mediastinum, Ewing's Sarcoma Metastatic, Ewing Family of Tumors, Ewing's Tumor Metastatic, Osteosarcoma, Metastatic, Osteosarcoma in Children, Rhabdoid Tumor, Lung Metastasis, Radiation for Children, SBRT for children, Stereotactic Body Radiotherapy, Pulmonary Metastasis, Lung Metastasis in Children, Pulmonary Metastasis in Children, Palliative Care