Trial Outcomes & Findings for Stereotactic Body Radiotherapy (SBRT) for Pulmonary Metastases in Ewing Sarcoma, Rhabdomyosarcoma, and Wilms Tumors (NCT NCT02581384)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

5 participants

Primary outcome timeframe

Up to 6 months

Results posted on

2021-04-30

Participant Flow

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 \[Phase I\]

Participant milestones

Participant milestones
Measure	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. Stereotactic Body Radiotherapy (SBRT)	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. Stereotactic Body Radiotherapy (SBRT)
Overall Study STARTED	3	2
Overall Study COMPLETED	3	2
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 2 Dose Level 2 [Phase I and II] n=5 Participants 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)
Age, Continuous	12 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants
Primary Tumor Histologies Ewing Sarcoma	3 Participants n=5 Participants
Primary Tumor Histologies Anaplastic Chordoma	1 Participants n=5 Participants
Primary Tumor Histologies Osteosarcoma	1 Participants n=5 Participants
Number of Lesions Two Lesions	3 Participants n=5 Participants
Number of Lesions One Lesion	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 2 Dose Level 2 [Phase I] n=3 Participants 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)	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. Stereotactic Body Radiotherapy (SBRT)
Number of Participants With Dose Limiting Toxicity [Phase I]	0 Participants	—

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Cohort 2 Dose Level 2 [Phase I] n=5 Participants 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)	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. Stereotactic Body Radiotherapy (SBRT)
Overall Response Rate [Phase II]	100 percentage of participants Interval 54.9 to 100.0	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Cohort 2 Dose Level 2 [Phase I] n=8 lesions 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)	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. Stereotactic Body Radiotherapy (SBRT)
Complete Response Rate [Phase II]	75 percentage of pulmonary lesions Interval 39.0 to 100.0	—

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Cohort 2 Dose Level 2 [Phase I] n=8 Lesions 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)	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. Stereotactic Body Radiotherapy (SBRT)
2 Year Local Control Rate [Phase II]	60 percentage of pulmonary lesions Interval 19.0 to 100.0	—

SECONDARY outcome

Timeframe: 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

Rate of distant lung failure-free survival defined lung failure or death from any cause at two years. Lung failure defined using established methods.

Outcome measures

Outcome measures
Measure	Cohort 2 Dose Level 2 [Phase I] n=5 Participants 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)	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. Stereotactic Body Radiotherapy (SBRT)
Percentage of Participants With 2-Year Failure-Free Survival [Phase II]	40 percentage of participants Interval 0.0 to 100.0	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 2 Dose Level 2 [Phase I] n=3 Participants 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)	Cohort 2 Dose Level 2 [Phase II] n=2 Participants 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)
Number of Participants With Grade 3 or Higher Adverse Events [Phase I and II]	0 Participants	0 Participants

Adverse Events

Cohort 2 Dose Level 2 [Phase I]

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 2 Dose Level 2 [Phase II]

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Cohort 2 Dose Level 2 [Phase I] n=3 participants at risk 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)	Cohort 2 Dose Level 2 [Phase II] n=2 participants at risk 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)
General disorders Fatigue	33.3% 1/3 • Number of events 1 • Up to 6 months post-treatment (6 months and 2 weeks) 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.	0.00% 0/2 • Up to 6 months post-treatment (6 months and 2 weeks) 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.
Respiratory, thoracic and mediastinal disorders Pneumonitis	33.3% 1/3 • Number of events 1 • Up to 6 months post-treatment (6 months and 2 weeks) 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.	0.00% 0/2 • Up to 6 months post-treatment (6 months and 2 weeks) 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.

Additional Information

Karen Marcus MD

Dana-Farber Cancer Institute

Phone: 16177328783

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place