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

Sponsor
Dana-Farber Cancer Institute (Other)
Overall Status
Terminated
CT.gov ID
NCT02581384
Collaborator
(none)
5
3
6
43
1.7
0

Study Details

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
5 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors
Actual Study Start Date :
Jan 1, 2017
Actual Primary Completion Date :
Aug 1, 2020
Actual Study Completion Date :
Aug 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1 Dose Level 1 [Phase I]

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)

Experimental: Cohort 1 Dose Level 2 [Phase I]

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)

Experimental: Cohort 1 Dose Level 3 [Phase I]

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)

Experimental: Cohort 2 Dose Level 2 [Phase I]

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)

Experimental: Cohort 2 Dose Level 3 [Phase I]

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)

Experimental: Cohort 2 Dose Level 2 [Phase II]

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)

Outcome Measures

Primary Outcome Measures

  1. 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.

  2. 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 Outcome Measures

  1. 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. 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.

  3. 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.

  4. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A to 21 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Boston Children's Hospital Boston Massachusetts United States 02115
2 Dana Farber Cancer Institute Boston Massachusetts United States 02115
3 Dana Farber Cancer Institute Boston Massachusetts United States 02215

Sponsors and Collaborators

  • Dana-Farber Cancer Institute

Investigators

  • Principal Investigator: Karen Marcus, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Karen J Marcus, MD FACR, Karen J Marcus, M.D., Boston Children's Hospital
ClinicalTrials.gov Identifier:
NCT02581384
Other Study ID Numbers:
  • 15-278
First Posted:
Oct 21, 2015
Last Update Posted:
Apr 30, 2021
Last Verified:
Apr 1, 2021

Study Results

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]
Pre-assignment Detail
Arm/Group Title Cohort 2 Dose Level 2 [Phase I] Cohort 2 Dose Level 2 [Phase II]
Arm/Group Description 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) 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)
Period Title: Overall Study
STARTED 3 2
COMPLETED 3 2
NOT COMPLETED 0 0

Baseline Characteristics

Arm/Group Title Cohort 2 Dose Level 2 [Phase I and II]
Arm/Group Description 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)
Overall Participants 5
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
12
Sex: Female, Male (Count of Participants)
Female
2
40%
Male
3
60%
Race/Ethnicity, Customized (Count of Participants)
White
3
60%
Other
1
20%
Unknown
1
20%
Primary Tumor Histologies (Count of Participants)
Ewing Sarcoma
3
60%
Anaplastic Chordoma
1
20%
Osteosarcoma
1
20%
Number of Lesions (Count of Participants)
Two Lesions
3
60%
One Lesion
2
40%

Outcome Measures

1. Primary Outcome
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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 2 Dose Level 2 [Phase I]
Arm/Group Description 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)
Measure Participants 3
Count of Participants [Participants]
0
0%
2. Primary Outcome
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

Outcome Measure Data

Analysis Population Description
It is pre-specified in the protocol that Phase I and Phase II populations for each cohort are combined for this analysis
Arm/Group Title Cohort 2 Dose Level 2 [Phase I and II]
Arm/Group Description 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)
Measure Participants 5
Number (90% Confidence Interval) [percentage of participants]
100
2000%
3. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
It is pre-specified in the protocol that Phase I and Phase II populations for each cohort are combined for this analysis
Arm/Group Title Cohort 2 Dose Level 2 [Phase I and II]
Arm/Group Description 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)
Measure Participants 5
Measure lesions 8
Number (95% Confidence Interval) [percentage of pulmonary lesions]
75
4. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
It is pre-specified in the protocol that Phase I and Phase II populations for each cohort are combined for this analysis
Arm/Group Title Cohort 2 Dose Level 2 [Phase I and II]
Arm/Group Description 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)
Measure Participants 5
Measure Lesions 8
Number (95% Confidence Interval) [percentage of pulmonary lesions]
60
5. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
It is pre-specified in the protocol that Phase I and Phase II populations for each cohort are combined for this analysis
Arm/Group Title Cohort 2 Dose Level 2 [Phase I and II]
Arm/Group Description 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)
Measure Participants 5
Number (95% Confidence Interval) [percentage of participants]
40
800%
6. Secondary Outcome
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)

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 2 Dose Level 2 [Phase I] Cohort 2 Dose Level 2 [Phase II]
Arm/Group Description 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) 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)
Measure Participants 3 2
Count of Participants [Participants]
0
0%
0
NaN

Adverse Events

Time Frame Up to 6 months post-treatment (6 months and 2 weeks)
Adverse Event Reporting Description Serious Adverse Events (SAE's) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Arm/Group Title Cohort 2 Dose Level 2 [Phase I] Cohort 2 Dose Level 2 [Phase II]
Arm/Group Description 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) 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)
All Cause Mortality
Cohort 2 Dose Level 2 [Phase I] Cohort 2 Dose Level 2 [Phase II]
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/3 (0%) 0/2 (0%)
Serious Adverse Events
Cohort 2 Dose Level 2 [Phase I] Cohort 2 Dose Level 2 [Phase II]
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/3 (0%) 0/2 (0%)
Other (Not Including Serious) Adverse Events
Cohort 2 Dose Level 2 [Phase I] Cohort 2 Dose Level 2 [Phase II]
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/3 (66.7%) 0/2 (0%)
General disorders
Fatigue 1/3 (33.3%) 1 0/2 (0%) 0
Respiratory, thoracic and mediastinal disorders
Pneumonitis 1/3 (33.3%) 1 0/2 (0%) 0

Limitations/Caveats

The study had small sample size / weak accrual.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Karen Marcus MD
Organization Dana-Farber Cancer Institute
Phone 16177328783
Email karen_marcus@dfci.harvard.edu
Responsible Party:
Karen J Marcus, MD FACR, Karen J Marcus, M.D., Boston Children's Hospital
ClinicalTrials.gov Identifier:
NCT02581384
Other Study ID Numbers:
  • 15-278
First Posted:
Oct 21, 2015
Last Update Posted:
Apr 30, 2021
Last Verified:
Apr 1, 2021