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

Phase 2TerminatedNCT02581384

Dana-Farber Cancer Institute5 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Ewing Sarcoma Rhabdomyosarcoma

Eligibility

Sex: ALLMax age: 21 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 6 weeks

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 6 months post-treatment (6 months and 2 weeks)