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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Cancer
• Intervention / Treatment: Radiation: Checkpoint blockade immunotherapy plus SBRT; Drug: Checkpoint blockade immunotherapy

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.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • UCSD Moores Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Checkpoint blockade immunotherapy plus SBRT; Checkpoint blockade immunotherapy (CBI) plus stereotactic body radiation therapy (SBRT)	Radiation: 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)
Active Comparator: Checkpoint blockade immunotherapy; Checkpoint blockade immunotherapy (CBI) alone	Drug: Checkpoint blockade immunotherapy; Approved Checkpoint blockade immunotherapy (including anti-CTLA-4 and anti-PD-1/PD-L1 antibodies)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Responses measured by RECIST at 16 weeks from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The time from starting treatment until death due to any cause.	Assessed at 5 years
Rate of Stable Disease	The rates of stable disease great than or equal to 6 months during and after SBRT in combination with CBI compared to CBI alone.	Assessed at 5 years
Number of Participants With Adverse Events	Adverse events assessed from time of first dose to treatment completion (approximately 1 year)	up to 5 years
Progression Free Survival	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	Assessed at 5 years

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Andrew Sharabi, MD, PhD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2016
• Primary Completion (Actual): August 16, 2021
• Study Completion (Actual): August 15, 2024

Study Registration Dates

• First Submitted: July 14, 2016
• First Submitted That Met QC Criteria: July 20, 2016
• First Posted (Estimated): July 25, 2016

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: stereotactic body radiation therapy; checkpoint blockade immunotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: 151570