Checkpoint Blockade Immunotherapy Combined With Stereotactic Body Radiation in Advanced Metastatic Disease

Randomized Phase II Study of Checkpoint Blockade Immunotherapy Combined With Stereotactic Body Radiation Therapy in Advanced Metastatic Disease

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02843165

Enrollment

106

Registered

2016-07-25

Start date

2016-09-02

Completion date

2024-08-15

Last updated

2025-09-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Metastatic Cancer

Keywords

stereotactic body radiation therapy, checkpoint blockade immunotherapy

Brief summary

The purpose of this study is to determine whether stereotactic body radiation therapy (SBRT) combined with checkpoint blockaded immunotherapy (CBI) will improve the response to the anticancer treatment compared to CBI alone in patients with advanced metastatic cancer.

Detailed description

Patients who will receive anti-PD-1/PD-L1 immunotherapy with at least 1 site of measurable metastatic disease which will not be irradiated will be candidates for the study. Patients will be randomized (1:1) to CBI combined with SBRT or CBI alone. SBRT at 9.5Gy x3 fractions will be delivered within 1-21 days of the start of first cycle of CBI. The first six patients will be treated and observed for toxicity in the safety run-in phase for 30 days after radiation before continuing with further accrual. Radiation dose reduction is allowed if necessary to meet tissue constraints (6Gyx3 Minimum Dose). Response rates will be determined from the non-irradiated lesion/lesions. Blood draws will be obtained to analyze anti-tumor immune responses.

Interventions

DRUGCheckpoint blockade immunotherapy

Approved Checkpoint blockade immunotherapy (including anti-CTLA-4 and anti-PD-1/PD-L1 antibodies)

RADIATIONCheckpoint blockade immunotherapy plus SBRT

SBRT at 28.5 Gy (9.5 Gy x3 fractions) will be delivered within 1 - 21 days of the start of Cycle 1 of the CBI plus CBI (approved CBIs including anti-CTLA-4 and anti-PD-1/PD-L1 antibodies)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Patient has one lesion that is treatable with SBRT. * Patient has at least 1 site of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria on computed tomography (CT) or Magnetic resonance imaging (MRI) which will not be irradiated. * Histological confirmation of malignancy (primary or metastatic tumor). * Patient may have any prior therapy allowed aside from having had prior radiotherapy to the treatment site. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. * Patient's screening laboratory values must meet protocol limits. * Patient must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

* Patient has had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. * Patient receiving any investigational or experimental agents other than immunotherapy. * Patient who has had any prior radiotherapy to the treatment site(s). * Patient is a pregnant woman (pregnant women are excluded from this study because radiation treatment has known potential for teratogenic or abortifacient effects). * Patient refuses to sign informed consent.

Design outcomes

Primary

Measure	Time frame	Description
Objective Response Rate	Responses measured by RECIST at 16 weeks from baseline	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary

Measure	Time frame	Description
Number of Participants With Adverse Events	up to 5 years	Adverse events assessed from time of first dose to treatment completion (approximately 1 year)
Progression Free Survival	Assessed at 5 years	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Overall Survival	Assessed at 5 years	The time from starting treatment until death due to any cause.
Rate of Stable Disease	Assessed at 5 years	The rates of stable disease great than or equal to 6 months during and after SBRT in combination with CBI compared to CBI alone.

Countries

United States

Participant flow

Recruitment details

Participants were recruited at the Moores Cancer Center of the University of California San Diego

Participants by arm

Arm	Count
Checkpoint Blockade Immunotherapy Plus SBRT Checkpoint blockade immunotherapy (CBI) plus stereotactic body radiation therapy (SBRT) Checkpoint blockade immunotherapy plus SBRT: SBRT at 28.5 Gy (9.5 Gy x3 fractions) will be delivered within 1 - 21 days of the start of Cycle 1 of the CBI plus CBI (approved CBIs including anti-CTLA-4 and anti-PD-1/PD-L1 antibodies)	58
Checkpoint Blockade Immunotherapy Checkpoint blockade immunotherapy (CBI) alone Checkpoint blockade immunotherapy: Approved Checkpoint blockade immunotherapy (including anti-CTLA-4 and anti-PD-1/PD-L1 antibodies)	48
Total	106

Baseline characteristics

Characteristic	Total	Checkpoint Blockade Immunotherapy Plus SBRT	Checkpoint Blockade Immunotherapy
Age, Continuous	61.92 years STANDARD_DEVIATION 12.99	61.03 years STANDARD_DEVIATION 12.9	63 years STANDARD_DEVIATION 13.5
Body System Breast	5 Participants	2 Participants	3 Participants
Body System Gastrointestinal	46 Participants	22 Participants	24 Participants
Body System Genitourinary	11 Participants	6 Participants	5 Participants
Body System Gynecologic	20 Participants	11 Participants	9 Participants
Body System Head and Neck	13 Participants	12 Participants	1 Participants
Body System Musculoskeletal	3 Participants	1 Participants	2 Participants
Body System Respiratory	3 Participants	1 Participants	2 Participants
Body System Skin	2 Participants	1 Participants	1 Participants
Body System Unknown	3 Participants	2 Participants	1 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants	7 Participants	8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	88 Participants	49 Participants	39 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants	2 Participants	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	12 Participants	6 Participants	6 Participants
Race (NIH/OMB) Black or African American	7 Participants	3 Participants	4 Participants
Race (NIH/OMB) More than one race	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	17 Participants	9 Participants	8 Participants
Race (NIH/OMB) White	68 Participants	38 Participants	30 Participants
Region of Enrollment United States	106 Participants	58 Participants	48 Participants
Sex: Female, Male Female	53 Participants	30 Participants	23 Participants
Sex: Female, Male Male	53 Participants	28 Participants	25 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	36 / 58	29 / 48
other Total, other adverse events	44 / 58	35 / 48
serious Total, serious adverse events	24 / 58	15 / 48

Outcome results

Primary

Objective Response Rate

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Time frame: Responses measured by RECIST at 16 weeks from baseline