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

Primary Purpose

Ewing Sarcoma, Rhabdomyosarcoma, Wilms Tumor

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Stereotactic Body Radiotherapy (SBRT)
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ewing Sarcoma focused on measuring 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

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Boston Children's Hospital
  • Dana Farber Cancer Institute
  • Dana Farber Cancer Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1 Dose Level 1 [Phase I]

Cohort 1 Dose Level 2 [Phase I]

Cohort 1 Dose Level 3 [Phase I]

Cohort 2 Dose Level 2 [Phase I]

Cohort 2 Dose Level 3 [Phase I]

Cohort 2 Dose Level 2 [Phase II]

Arm Description

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.

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.

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.

Participants with Ewing sarcoma or rhabdomyosarcoma. SBRT Dose Levels for each target lesion are three 10 Gy fractions for 30 Gy total.

Participants with Ewing sarcoma or rhabdomyosarcoma.SBRT Dose Levels for each target lesion are three 12 Gy fractions for 36 Gy total.

Participants with Ewing sarcoma or rhabdomyosarcoma. SBRT Dose Levels for each target lesion are three 10 Gy fractions for 30 Gy total.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
October 19, 2015
Last Updated
April 5, 2021
Sponsor
Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02581384
Brief Title
Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors
Official Title
Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Terminated
Why Stopped
The study closed primarily due to weak accrual, as well as study design limitations.
Study Start Date
January 2017 (Actual)
Primary Completion Date
August 2020 (Actual)
Study Completion Date
August 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1 Dose Level 1 [Phase I]
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 1 Dose Level 2 [Phase I]
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 1 Dose Level 3 [Phase I]
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2 Dose Level 2 [Phase I]
Arm Type
Experimental
Arm Description
Participants with Ewing sarcoma or rhabdomyosarcoma. SBRT Dose Levels for each target lesion are three 10 Gy fractions for 30 Gy total.
Arm Title
Cohort 2 Dose Level 3 [Phase I]
Arm Type
Experimental
Arm Description
Participants with Ewing sarcoma or rhabdomyosarcoma.SBRT Dose Levels for each target lesion are three 12 Gy fractions for 36 Gy total.
Arm Title
Cohort 2 Dose Level 2 [Phase II]
Arm Type
Experimental
Arm Description
Participants with Ewing sarcoma or rhabdomyosarcoma. SBRT Dose Levels for each target lesion are three 10 Gy fractions for 30 Gy total.
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Body Radiotherapy (SBRT)
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicity [Phase I]
Description
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
Title
Overall Response Rate [Phase II]
Description
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 Outcome Measure Information:
Title
Complete Response Rate [Phase II]
Description
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
Title
2 Year Local Control Rate [Phase II]
Description
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
Title
Percentage of Participants With 2-Year Failure-Free Survival [Phase II]
Description
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
Title
Number of Participants With Grade 3 or Higher Adverse Events [Phase I and II]
Description
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)

10. Eligibility

Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen Marcus, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
33305087
Citation
Liu KX, Chen YH, Kozono D, Mak RH, Boyle PJ, Janeway KA, Mullen EA, Marcus KJ. Phase I/II Study of Stereotactic Body Radiation Therapy for Pulmonary Metastases in Pediatric Patients. Adv Radiat Oncol. 2020 Sep 23;5(6):1267-1273. doi: 10.1016/j.adro.2020.09.004. eCollection 2020 Nov-Dec.
Results Reference
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Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors

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