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

Phase 2

Active, not recruiting

• Conditions: Metastatic Cancer
• Interventions: Drug: Checkpoint blockade immunotherapy; Radiation: Checkpoint blockade immunotherapy plus SBRT

• Registration Number: NCT02843165
• Lead Sponsor: University of California, San Diego

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.

Study Timeline

• Study Start: 2016-05-03
• Study First Submitted: 2016-07-14
• Study First Submitted QC: 2016-07-20
• Study First Posted: 2016-07-25
• Primary Completion: 2021-08-16
• Status Verified: 2023-06
• Study Completion: 2023-06
• Last Update Submitted: 2023-06-03
• Last Update Posted: 2023-06-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 146

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Checkpoint blockade immunotherapy	Checkpoint blockade immunotherapy	Checkpoint blockade immunotherapy (CBI) alone
Checkpoint blockade immunotherapy plus SBRT	Checkpoint blockade immunotherapy plus SBRT	Checkpoint blockade immunotherapy (CBI) plus stereotactic body radiation therapy (SBRT)

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	Responses measured by RECIST at 16 weeks from baseline	Complete response plus partial response

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Assessed at 5 years	The time from starting treatment until death due to any cause.
Progression Free Survival	Assessed at 5 years	The time from starting treatment to the time of first documented tumor progression or death due to any cause, whichever occurs first
Safety and toxicity of combined CBI plus SBRT	Evaluated at each treatment cycle (each cycle is 2 or 3 weeks), then at 8 weeks, 16 weeks, 6 months, 12 months, 18 months, and 24 months, then every 6 months up to 2 years	Adverse events assessed from time of first dose to treatment completion (approximately 1 year)
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.
Change in anti-tumor immune response	At week 3 or 4 after starting treatment (prior to Cycle 2 of CBI) and at 2 months. Each cycle is 2 or 3 weeks.	Lesion and blood assays performed in the lab.

Trial Locations

Locations (1)

UCSD Moores Cancer Center; 🇺🇸 La Jolla, California, United States