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

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ClinicalTrials.gov Identifier: NCT02843165
Recruitment Status : Active, not recruiting
First Posted : July 25, 2016
Last Update Posted : May 18, 2022
Information provided by (Responsible Party):
Andrew Sharabi, 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.

Condition or disease Intervention/treatment Phase
Metastatic Cancer Drug: CBI Radiation: CBI plus SBRT Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 146 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of Checkpoint Blockade Immunotherapy Combined With Stereotactic Body Radiation Therapy in Advanced Metastatic Disease
Actual Study Start Date : May 3, 2016
Actual Primary Completion Date : August 16, 2021
Estimated Study Completion Date : January 2023

Arm Intervention/treatment
Experimental: CBI plus SBRT
Checkpoint blockade immunotherapy (CBI) plus stereotactic body radiation therapy (SBRT)
Radiation: CBI 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: CBI
Checkpoint blockade immunotherapy (CBI)
Drug: CBI
Approved CBIs (including anti-CTLA-4 and anti-PD-1/PD-L1 antibodies)

Primary Outcome Measures :
  1. Objective Response Rate [ Time Frame: Responses measured by RECIST at 16 weeks from baseline ]
    Complete response plus partial response

Secondary Outcome Measures :
  1. Safety and toxicity of combined CBI plus SBRT [ Time Frame: 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)

  2. Progression Free Survival [ Time Frame: 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

  3. Overall Survival [ Time Frame: Assessed at 5 years ]
    The time from starting treatment until death due to any cause.

  4. Rate of Stable Disease [ Time Frame: 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.

  5. Change in anti-tumor immune response [ Time Frame: 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. ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02843165

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United States, California
UCSD Moores Cancer Center
La Jolla, California, United States, 92093
Sponsors and Collaborators
University of California, San Diego
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Principal Investigator: Andrew Sharabi, MD, PhD University of California, San Diego
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Responsible Party: Andrew Sharabi, Assistant Clinical Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT02843165    
Other Study ID Numbers: 151570
First Posted: July 25, 2016    Key Record Dates
Last Update Posted: May 18, 2022
Last Verified: May 2022
Keywords provided by Andrew Sharabi, University of California, San Diego:
stereotactic body radiation therapy
checkpoint blockade immunotherapy
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes