Clear Cell Renal Cell Carcinoma, Ewing Sarcoma, Non-Rhabdomyosarcoma Soft Tissue Sarcoma, Nos, Osteosarcoma, Renal Tumor, Rhabdoid Tumor, Rhabdomyosarcoma, Sarcoma, Sarcoma, Ewing, Soft Tissue Sarcoma, Wilms Tumor
Conditions
Keywords
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, Comfort Care, Palliative Care
Brief summary
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
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.
Interventions
RADIATIONStereotactic Body Radiotherapy (SBRT)
Sponsors
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicity [Phase I] | Up to 6 months | 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. |
| Overall Response Rate [Phase II] | 6 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate [Phase II] | 6 weeks | 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. |
| 2 Year Local Control Rate [Phase II] | 24 Months | 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. |
| Percentage of Participants With 2-Year Failure-Free Survival [Phase II] | 24 months | Rate of distant lung failure-free survival defined lung failure or death from any cause at two years. Lung failure defined using established methods. |
| Number of Participants With Grade 3 or Higher Adverse Events [Phase I and II] | Up to 6 months post-treatment (6 months and 2 weeks) | Grade 3 or higher adverse events as defined by controlled terminology criteria for adverse events (CTCAE) version 4. |
Countries
United States
Participant flow
Recruitment details
January 2017 to December 2018. No participants were in enrolled in Cohort 1 Dose Level 1 \[Phase I\], Cohort 1 Dose Level 2 \[Phase I\], Cohort 1 Dose Level 3 \[Phase I\], and Cohort 2 Dose Level 3 \[Phase I\]
Participants by arm
| Arm | Count |
|---|---|
| Cohort 2 Dose Level 2 [Phase I and II] Participants with Ewing sarcoma or rhabdomyosarcoma. SBRT Dose Levels for each target lesion are three 10 Gy fractions for 30 Gy total.
Stereotactic Body Radiotherapy (SBRT) | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Cohort 2 Dose Level 2 [Phase I and II] |
|---|---|
| Age, Continuous | 12 years |
| Number of Lesions One Lesion | 2 Participants |
| Number of Lesions Two Lesions | 3 Participants |
| Primary Tumor Histologies Anaplastic Chordoma | 1 Participants |
| Primary Tumor Histologies Ewing Sarcoma | 3 Participants |
| Primary Tumor Histologies Osteosarcoma | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants |
| Race/Ethnicity, Customized White | 3 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 2 / 3 | 0 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 2 Dose Level 2 [Phase I] | Number of Participants With Dose Limiting Toxicity [Phase I] | 0 Participants |
Primary
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
Population: It is pre-specified in the protocol that Phase I and Phase II populations for each cohort are combined for this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2 Dose Level 2 [Phase I] | Overall Response Rate [Phase II] | 100 percentage of participants |
Secondary
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
Population: It is pre-specified in the protocol that Phase I and Phase II populations for each cohort are combined for this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2 Dose Level 2 [Phase I] | 2 Year Local Control Rate [Phase II] | 60 percentage of pulmonary lesions |
Secondary
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
Population: It is pre-specified in the protocol that Phase I and Phase II populations for each cohort are combined for this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2 Dose Level 2 [Phase I] | Complete Response Rate [Phase II] | 75 percentage of pulmonary lesions |
Secondary
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)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 2 Dose Level 2 [Phase I] | Number of Participants With Grade 3 or Higher Adverse Events [Phase I and II] | 0 Participants |
| Cohort 2 Dose Level 2 [Phase II] | Number of Participants With Grade 3 or Higher Adverse Events [Phase I and II] | 0 Participants |
Secondary
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
Population: It is pre-specified in the protocol that Phase I and Phase II populations for each cohort are combined for this analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2 Dose Level 2 [Phase I] | Percentage of Participants With 2-Year Failure-Free Survival [Phase II] | 40 percentage of participants |