SBRT + PD-1/PDL-1 Inhibiting Therapy for Advanced Solid T... | NCT03220854

ID	Type	Description	Link
P30CA016059	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
A: SBRT (body) irradiation only	Experimental	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations	Radiation: Stereotactic radiotherapy Other: Biological: humanized anti-PD-1 monoclonal antibody Other: Biological: humanized anti-PD-L1 monoclonal antibody
B: Patients receiving SBRT and SRS (body and brain) irradiation	Experimental	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations	Radiation: Stereotactic radiotherapy Other: Biological: humanized anti-PD-1 monoclonal antibody Other: Biological: humanized anti-PD-L1 monoclonal antibody
C: Patients receiving SRS (brain) irradiation only	Experimental	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations	Radiation: Stereotactic radiotherapy Other: Biological: humanized anti-PD-1 monoclonal antibody Other: Biological: humanized anti-PD-L1 monoclonal antibody

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Stereotactic radiotherapy	Radiation	Treatment will be planned to deliver a total of 18 to 60 Gy to the planning target volume (PTV) in 3 to 5 fractions over 1 to 2 weeks.	A: SBRT (body) irradiation only

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Patients With Improved Disease Control	Number of patients with improved disease control at 24 weeks following RT [Time Frame: up to 24 weeks following RT] 1a. Number of participants with improved disease control (SD, PR or CR) at 24 weeks per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) 1b. For participants enrolled with brain metastases: number of participants with improved disease (SD, PR or CR) control at 24 weeks per per Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM)	Up to 24 weeks following SRT

Secondary Outcomes

Measure	Description	Time Frame
Number of Patients Alive and Free From Progression at 24 Weeks Following SRT Per Unidimensional Immune-related Response Criteria (irRC)	Number of participants alive and without progression (irSD+irPR+irCR) at 24 weeks post-RT per unidimensional immune-related response criteria (irRC) 1b. For participants enrolled with brain metastases: number of participants alive and without progression (SD+PR+CR) at 24 weeks post-RT per immune Response Assessment in Neuro-Oncology (iRANO)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Pathologically-proven diagnosis of a solid tumor malignancy
One of the following criteria must be met:
Clinical or radiographic evidence of disease control (defined as best response of stable disease (SD) or partial response (PR) or combination of both for ≥ 16 weeks) without evidence of complete response (CR) or progression OR
Clinical or radiographic evidence of disease progression during treatment with PD-1 or PD-L1 inhibiting therapy, following previous tumor response (CR, PR, or SD for ≥ 16 weeks) to PD-1 or PD-L1 inhibiting therapy, and, for patients who discontinued PD-1 or PD-L1 inhibiting therapy during response to therapy, disease progression must have occurred following at least 8 weeks of re-treatment with PD-1 or PD-L1 inhibiting therapy Note: Both the treating medical oncologist and radiation oncologist must be in agreement with determination of disease progression.
Administration of a PD-1 or PD-L1 inhibitor within 60 days prior to study registration
Determination by the treating radiation oncologist that the patient is a candidate for SRT (ie, radiation therapy with a stereotactic setup) Note: All brain metastases will receive stereotactic radiotherapy (SRT).
The total number of tumors requiring SRT must be ≤ 5 Note: Regardless of the number of brain metastases that will be treated with SRT, the brain metastases will be considered to be one tumor.
Measurable disease by RECIST v1.1 that will not undergo SRT and that is amenable to monitoring Note: all brain metastases will receive SRT. Therefore, a patient with brain metastases that will be treated with SRT must also have extracranial disease that will not undergo SRT and that is amenable to monitoring
Determination by the treating medical oncologist that the patient is a candidate to continue the PD-1 or PD-L1 inhibiting therapy that had previously provided disease control
Age ≥ 18 years
Karnofsky Performance Status score of ≥ 60 %
A woman of childbearing potential (WCBP), defined as a woman who is < 60 years of age and has not had a hysterectomy, must have a documented negative serum pregnancy test within 14 days prior to initiating study treatment
Ability to understand and willingness to sign the consent form

Exclusion Criteria:

Other anti-cancer therapy administered between the time of tumor response to PD-1 or PD-L1 therapy and time of study enrollment Note: Patients treated with a combination of PD-1 or PD-L1 inhibiting therapy and other immunotherapy are eligible; patients taking hormonal anti-cancer therapies or steroids for central nervous system (CNS) edema management that, in the opinion of the investigator, are appropriate to continue are eligible.
Any prior PD-1/PD-L1 therapy-related AE that, in the opinion of the investigator, warrants exclusion from participation in this trial
Administration of any investigational agent within 4 weeks prior to initiating study treatment
Known active hepatitis B or C
Pregnancy or breastfeeding
Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements

Name	Affiliation	Role
Alfredo Urdaneta, M.D.	Massey Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Virginia Commonwealth University/Massey Cancer Center		Richmond	Virginia	23298	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	A: Patients Receiving SBRT (Body) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Dec 19, 2018

Arm/Group Information

ID	Title	Description
BG000	A: Patients Receiving SBRT (Body) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.
BG001	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.
BG002	C: Patients Receiving SRS (Brain) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0004 BG0010 BG0021 BG0035

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020 BG003

Age, Continuous

Mean

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00068(59 to 71) BG00267(67 to 67) BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0002 BG0020 BG003

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0020 BG003

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0020 BG003

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0004 BG0021 BG003

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Patients With Improved Disease Control

Number of patients with improved disease control at 24 weeks following RT [Time Frame: up to 24 weeks following RT] 1a. Number of participants with improved disease control (SD, PR or CR) at 24 weeks per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) 1b. For participants enrolled with brain metastases: number of participants with improved disease (SD, PR or CR) control at 24 weeks per per Response Assessment in Neuro-Oncology for Brain Metastases (RANO-BM)

No participants enrolled in Arm B

Posted

Count of Participants

Participants

Up to 24 weeks following SRT

ID	Title	Description
OG000	A: SBRT (Body) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations
OG001	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations
OG002	C: Patients Receiving SRS (Brain) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations

Units	Counts
Participants	OG0004 OG0010 OG0021

Title

Denominators

Categories

1a: Number of participants with improved disease control

Title	Measurements
Complete Response	OG0000 OG0010 OG0020
Partial Response

Secondary

Number of Patients Alive and Free From Progression at 24 Weeks Following SRT Per Unidimensional Immune-related Response Criteria (irRC)

Number of participants alive and without progression (irSD+irPR+irCR) at 24 weeks post-RT per unidimensional immune-related response criteria (irRC)

1b. For participants enrolled with brain metastases: number of participants alive and without progression (SD+PR+CR) at 24 weeks post-RT per immune Response Assessment in Neuro-Oncology (iRANO)

No participants were enrolled in Arm B

Posted

Count of Participants

Participants

Up to 24 weeks following SRT

ID	Title	Description
OG000	A: Patients Receiving SBRT (Body) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations
OG001	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.

Secondary

Number of Participants With Treatment Response in Irradiated Tumor Sites

Number of participants with treatment response in irradiated tumor sites at 24 weeks post-RT.

No participants enrolled on Arm B.

Posted

Count of Participants

Participants

Up to 24 weeks following SRT

ID	Title	Description
OG000	A: Patients Receiving SBRT (Body) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations
OG001	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.
OG002	C: Patients Receiving SRS (Brain) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.

Secondary

Number of Participants With Treatment Response in Non-irradiated Tumor Sites

Number of participants with treatment response in non-irradiated tumor sites at 24 weeks post-RT

No participants enrolled on Arm B

Posted

Count of Participants

Participants

Up to 24 weeks post-RT

ID	Title	Description
OG000	A: SBRT (Body) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations
OG001	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations
OG002	C: Patients Receiving SRS (Brain) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations

Secondary

Number of Patients Alive

Number of patients who are alive at 2 years after completion of SRT

No participants enrolled on Arm B

Posted

Count of Participants

Participants

2 years following SRT

ID	Title	Description
OG000	A: Patients Receiving SBRT (Body) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations
OG001	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.
OG002	C: Patients Receiving SRS (Brain) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.

Secondary

Number of Participants With Grade 3 or Greater Toxicity

Number of participants with grade 3 or greater toxicity from the regimen through 8 weeks following RT

No participants enrolled in Arm B

Posted

Count of Participants

Participants

Through 8 weeks following SRT

ID	Title	Description
OG000	A: Patients Receiving SBRT (Body) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations
OG001	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.
OG002	C: Patients Receiving SRS (Brain) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.

Secondary

Number of Participants With Immune-related Toxicity From the Regimen

Number participants with immune-related AEs (irAEs) that require both checkpoint-inhibitor discontinuation and initiation of steroids reported per CTCAE v5.0

No participants enrolled on Arm B

Posted

Count of Participants

Participants

Up to 2 years following RT

ID	Title	Description
OG000	A: Patients Receiving SBRT (Body) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations
OG001	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.
OG002	C: Patients Receiving SRS (Brain) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.

Secondary

Radiobiological Signatures Associated With the Regimen

Number participants with samples collected and number of participants with samples analyzed for immunologic effects of the regimen

No participants enrolled on Arm B

Posted

Count of Participants

Participants

Up to 52 weeks post SRT

ID	Title	Description
OG000	A: Patients Receiving SBRT (Body) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations
OG001	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.
OG002	C: Patients Receiving SRS (Brain) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	A: Patients Receiving SBRT (Body) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations	1	4	4	3	4
EG001	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.	0	0	0	0	0
EG002	C: Patients Receiving SRS (Brain) Irradiation Only	Patients will receive a standard treatment regimen of SRT (refer to Section 6.3). The term SRT encompasses all radiotherapy using a stereotactic setup, both stereotactic radiosurgery (SRS) for metastatic lesions in the brain and stereotactic body radiotherapy (SBRT) for SRT delivered to all other locations.	0	1	1	0	1

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Aspartate Aminotransferase Increased	Investigations	CTCAE 5.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected0 at risk EG0020 events0 affected1 at risk
Fatigue	General disorders	CTCAE 5.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected0 at risk EG0020 events0 affected1 at risk
Lymphocyte Count Decreased	Investigations	CTCAE 5.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected0 at risk EG0020 events0 affected1 at risk

ID	Term
D011878	Radiotherapy
D013812	Therapeutics
D013238	Stereotaxic Techniques
D019635	Neurosurgical Procedures
D013514	Surgical Procedures, Operative
D008919	Investigative Techniques