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

Metastatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02843165
• Other study ID #: 151570
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 3, 2016
• Est. completion date: June 2023

Study information

• Verified date: June 2023
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 146
• Est. completion date: June 2023
• Est. primary completion date: August 16, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis

Intervention

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

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)

Locations

Country	Name	City	State
United States	UCSD Moores Cancer Center	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	Complete response plus partial response	Responses measured by RECIST at 16 weeks from baseline
Secondary	Safety and toxicity of combined CBI plus SBRT	Adverse events assessed from time of first dose to treatment completion (approximately 1 year)	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
Secondary	Progression Free Survival	The time from starting treatment to the time of first documented tumor progression or death due to any cause, whichever occurs first	Assessed at 5 years
Secondary	Overall Survival	The time from starting treatment until death due to any cause.	Assessed at 5 years
Secondary	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
Secondary	Change in anti-tumor immune response	Lesion and blood assays performed in the lab.	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.