CompletedNCT03220854Updated Jan 10, 2022Results posted

SBRT + PD-1/PDL-1 Inhibiting Therapy for Advanced Solid Tumors After Dz Control on PD-1/PDL-1 Tx

A Phase 2 interventional study of Stereotactic radiotherapy and Biological: humanized anti-PD-1 monoclonal antibody in Solid Tumor, sponsored by Virginia Commonwealth University. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-01-10.

Sponsored by Virginia Commonwealth University · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 5
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

The purpose of this study is to find out if having radiation therapy and continuing immunotherapy can improve the benefit of immunotherapy. There have been reports of patients who were treated with radiation therapy that not only caused the treated tumors to shrink or stop growing, but also resulted in tumors that had not been treated in other parts of the body to shrink or stop growing. This effect is thought to be brought about by cells in the body's immune system that become active as a result of the effects of radiation therapy. If radiation therapy can stimulate the immune system, it may be possible for immunotherapy to be helpful again in treating a cancer that the immunotherapy drug helped treat before. This study will also check if receiving immunotherapy at the end of radiation therapy has any effect on the side effects of radiation therapy or immunotherapy.

Read the detailed description

Stereotactic radiotherapy (SRT) will be delivered in up to 10 treatment fractions over 1 to 2 weeks. Patients will continue to receive the same FDA-approved programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor that they had been receiving at the time of disease progression through 52 weeks following completion of SRT.

Correlative blood samples will be collected at baseline, prior to the second SRT fraction, after the last SRT fraction (on the same day), and at 8, 24, and 52 weeks after the last SRT fraction. These samples will be used to determine the mechanistic immunologic effects of therapy.

Conditions studied

Solid Tumor

In context

Lead sponsor

Virginia Commonwealth University is the lead sponsor of 648 studies on the registry; 82 are open to participants now.

Of its 90 completed or terminated interventional studies of FDA-regulated products, 64 (71%) have results posted.

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Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 5 participants (actual)

Study arms

Experimental
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
Radiation: Stereotactic radiotherapy · Other: Biological: humanized anti-PD-1 monoclonal antibody · Other: Biological: humanized anti-PD-L1 monoclonal antibody
Experimental
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
Radiation: Stereotactic radiotherapy · Other: Biological: humanized anti-PD-1 monoclonal antibody · Other: Biological: humanized anti-PD-L1 monoclonal antibody
Experimental
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
Radiation: Stereotactic radiotherapy · Other: Biological: humanized anti-PD-1 monoclonal antibody · Other: Biological: humanized anti-PD-L1 monoclonal antibody

Interventions

RadiationStereotactic radiotherapy
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.
Also known as: SRT
OtherBiological: humanized anti-PD-1 monoclonal antibody
Standard of Care - patient will continue to be given the same PD-1 inhibitor they were receiving prior to study registration
Also known as: PD-1
OtherBiological: humanized anti-PD-L1 monoclonal antibody
Standard of Care - patient will continue to be given the same PD-L1 inhibitor they were receiving prior to study registration
Also known as: PD-L1

What researchers measure

Primary outcomes

Number of Patients With Improved Disease Control
1. 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)
Time frame: Up to 24 weeks following SRT

Secondary outcomes

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)
Time frame: Up to 24 weeks following SRT
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.
Time frame: Up to 24 weeks following SRT
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
Time frame: Up to 24 weeks post-RT
Number of Patients Alive
Number of patients who are alive at 2 years after completion of SRT
Time frame: 2 years following SRT
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
Time frame: Through 8 weeks following SRT
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
Time frame: Up to 2 years following RT
Radiobiological Signatures Associated With the Regimen
Number participants with samples collected and number of participants with samples analyzed for immunologic effects of the regimen
Time frame: Up to 52 weeks post SRT

Results

Posted Jan 15, 2021

Limitations and caveats

Incomplete objectives due to early closure to accrual of trial.

Participant flow

No participants enrolled in Arm B.

Participant flow — Overall Study
Milestone	A: Patients Receiving SBRT (Body) Irradiation Only	C: Patients Receiving SRS (Brain) Irradiation Only
Started	4	1
Completed	4	1
Not completed	0	0

Outcome measures

PrimaryNumber of Patients With Improved Disease Control

1. 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)

Time frame:: Up to 24 weeks following SRT
Reported as:: Count of participants · Participants

Number of Patients With Improved Disease Control
Participants	A: SBRT (Body) Irradiation Only	C: Patients Receiving SRS (Brain) Irradiation Only
1a: Number of participants with improved disease control — Complete Response	0	0
1a: Number of participants with improved disease control — Partial Response	0	0
1a: Number of participants with improved disease control — Stable Disease	0	0
1a: Number of participants with improved disease control — Progression at or before 24 Weeks	2	1
1a: Number of participants with improved disease control — Not Evaluable	2	0
1b: Participants enrolled with brain metastases number of participants with improved disease control — Complete Response	NA	0
1b: Participants enrolled with brain metastases number of participants with improved disease control — Partial Response	NA	0
1b: Participants enrolled with brain metastases number of participants with improved disease control — Stable Disease	NA	1
1b: Participants enrolled with brain metastases number of participants with improved disease control — Progression at or before 24 Weeks	NA	0
1b: Participants enrolled with brain metastases number of participants with improved disease control — Not Evaluable	NA	0

SecondaryNumber 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)

Time frame:: Up to 24 weeks following SRT
Reported as:: Count of participants · Participants

Number of Patients Alive and Free From Progression at 24 Weeks Following SRT Per Unidimensional Immune-related Response Criteria (irRC)
Participants	A: Patients Receiving SBRT (Body) Irradiation Only	C: Patients Receiving SRS (Brain) Irradiation Only
1a. Number of participants alive and without progression — Progression Free Survival per irRC at 24 wks	0	0
1a. Number of participants alive and without progression — Progression per irRC at or before 24 Weeks	1	1
1a. Number of participants alive and without progression — Not Evaluable	3	0
1b.For participants enrolled with brain metastases — Progression Free Survival per irRC at 24 wks	NA	1
1b.For participants enrolled with brain metastases — Progression per irRC at or before 24 Weeks	NA	0
1b.For participants enrolled with brain metastases — Not Evaluable	NA	0

SecondaryNumber of Participants With Treatment Response in Irradiated Tumor Sites

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

Time frame:: Up to 24 weeks following SRT
Reported as:: Count of participants · Participants

Number of Participants With Treatment Response in Irradiated Tumor Sites
Participants	A: Patients Receiving SBRT (Body) Irradiation Only	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	C: Patients Receiving SRS (Brain) Irradiation Only
Complete Response at Irradiated Sites	0	—	0
Partial Response at Irradiated Sites	0	—	1
Stable Disease at Irradiated Sites	0	—	0
Not assessed at week 24 due to overall progression	2	—	0
Not Evaluable	2	—	0

SecondaryNumber 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

Time frame:: Up to 24 weeks post-RT
Reported as:: Count of participants · Participants

Number of Participants With Treatment Response in Non-irradiated Tumor Sites
Participants	A: SBRT (Body) Irradiation Only	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	C: Patients Receiving SRS (Brain) Irradiation Only
Complete Response at non-irradiated sites	0	—	0
Partial Response at non-irradiated sites	0	—	0
Stable Disease at non-irradiated sites	0	—	0
Progression at non-irradiated sites at or before 24 weeks	2	—	1
Not Evaluable	2	—	0

SecondaryNumber of Patients Alive

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

Time frame:: 2 years following SRT
Reported as:: Count of participants · Participants

Number of Patients Alive
Participants	A: Patients Receiving SBRT (Body) Irradiation Only	C: Patients Receiving SRS (Brain) Irradiation Only
Number of participants meeting 2 year survival threshold	2	1
Number of participants not meeting 2 year survival threshold	1	0
Not evaluable	1	0

SecondaryNumber 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

Time frame:: Through 8 weeks following SRT
Reported as:: Count of participants · Participants

Number of Participants With Grade 3 or Greater Toxicity
Participants	A: Patients Receiving SBRT (Body) Irradiation Only	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	C: Patients Receiving SRS (Brain) Irradiation Only
Number of Participants With Grade 3 or Greater Toxicity	1	0	0

SecondaryNumber 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

Time frame:: Up to 2 years following RT
Reported as:: Count of participants · Participants

Number of Participants With Immune-related Toxicity From the Regimen
Participants	A: Patients Receiving SBRT (Body) Irradiation Only	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	C: Patients Receiving SRS (Brain) Irradiation Only
Participants with immune-related AEs (irAEs)	1	—	0
Participants with no immune related AE's (irAEs)	2	—	1
Not Evaluable	1	—	0

SecondaryRadiobiological Signatures Associated With the Regimen

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

Time frame:: Up to 52 weeks post SRT
Reported as:: Count of participants · Participants

Radiobiological Signatures Associated With the Regimen
Participants	A: Patients Receiving SBRT (Body) Irradiation Only	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	C: Patients Receiving SRS (Brain) Irradiation Only
Number of participants with samples collected	3	—	1
Number of participants with samples analyzed for immunologic effects of the regimen	0	0	0
Number of participants with no samples collected	1	—	0

Adverse events

Collected over Adverse Event data was collected from the time of first SRT fraction and continued until 8 weeks following completion of SRT.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
A: Patients Receiving SBRT (Body) Irradiation Only	1/4 (25%)	0/4 (0%)	3/4 (75%)
B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	—	—	—
C: Patients Receiving SRS (Brain) Irradiation Only	0/1 (0%)	0/1 (0%)	0/1 (0%)

Most frequent other events

Most frequent other events
Event	A: Patients Receiving SBRT (Body) Irradiation Only	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	C: Patients Receiving SRS (Brain) Irradiation Only
Aspartate Aminotransferase IncreasedInvestigations	1/4	—	0/1
FatigueGeneral disorders	1/4	—	0/1
Lymphocyte Count DecreasedInvestigations	1/4	—	0/1

Baseline characteristics

No participants enrolled on Arm B

Age, Categorical
Age, Categorical(Participants)	A: Patients Receiving SBRT (Body) Irradiation Only	C: Patients Receiving SRS (Brain) Irradiation Only	Total
<=18 years	0	0	0
Between 18 and 65 years	1	0	1
>=65 years	3	1	4

Age, Continuous
Age, Continuous(years)	A: Patients Receiving SBRT (Body) Irradiation Only	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	C: Patients Receiving SRS (Brain) Irradiation Only	Total
Mean	68 (59 to 71)	—	67 (67 to 67)	67.8 (59 to 71)

Sex: Female, Male
Sex: Female, Male(Participants)	A: Patients Receiving SBRT (Body) Irradiation Only	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	C: Patients Receiving SRS (Brain) Irradiation Only	Total
Female	2	—	0	2
Male	2	—	1	3

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	A: Patients Receiving SBRT (Body) Irradiation Only	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	C: Patients Receiving SRS (Brain) Irradiation Only	Total
Hispanic or Latino	0	—	0	0
Not Hispanic or Latino	4	—	1	5
Unknown or Not Reported	0	—	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	A: Patients Receiving SBRT (Body) Irradiation Only	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	C: Patients Receiving SRS (Brain) Irradiation Only	Total
American Indian or Alaska Native	0	—	0	0
Asian	0	—	1	1
Native Hawaiian or Other Pacific Islander	0	—	0	0
Black or African American	0	—	0	0
White	4	—	0	4
More than one race	0	—	0	0
Unknown or Not Reported	0	—	0	0

Region of Enrollment
Region of Enrollment(participants)	A: Patients Receiving SBRT (Body) Irradiation Only	B: Patients Receiving SBRT and SRS (Body and Brain) Irradiation	C: Patients Receiving SRS (Brain) Irradiation Only	Total
United States	4	—	1	5

Study locations

1 site

Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia 23298, United States

References and documents

Study documents

Protocol and statistical analysis plan · Dec 19, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reached

Ran from Oct 2017 to primary completion in Jan 2020, 27 months.

Results were first posted in Jan 2021, 11 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Jul 14, 2017
First posted: Jul 18, 2017
StartActual: Oct 10, 2017
Primary completionActual: Jan 27, 2020
CompletionActual: Sep 22, 2021
Results first posted: Jan 15, 2021
Last update: Jan 10, 2022

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Jan 10, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03220854
Lead sponsor: Virginia Commonwealth University
Collaborators: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Jul 18, 2017
Start date: Oct 10, 2017
Primary completion: Jan 27, 2020
Completion: Sep 22, 2021
Results posted: Jan 15, 2021
Last update: Jan 10, 2022

Study contacts

Alfredo Urdaneta, M.D.

principal investigator · Massey Cancer Center

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Dec 2021. You cannot join it, but the record below documents what was studied.

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