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

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

Tracking Information

• First Submitted Date: July 14, 2016
• First Posted Date: July 25, 2016
• Last Update Posted Date: May 18, 2022
• Actual Study Start Date: May 3, 2016
• Actual Primary Completion Date: August 16, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 20, 2016)

Objective Response Rate [ Time Frame: Responses measured by RECIST at 16 weeks from baseline ]

Complete response plus partial response

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 20, 2016)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Checkpoint Blockade Immunotherapy Combined With Stereotactic Body Radiation in Advanced Metastatic Disease
• Official Title: Randomized Phase II Study of Checkpoint Blockade Immunotherapy Combined With Stereotactic Body Radiation Therapy in Advanced Metastatic Disease
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Cancer

Intervention

• Drug: CBI
  Approved CBIs (including anti-CTLA-4 and anti-PD-1/PD-L1 antibodies)
• 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)

Study Arms

• Experimental: CBI plus SBRT
  Checkpoint blockade immunotherapy (CBI) plus stereotactic body radiation therapy (SBRT)
  Intervention: Radiation: CBI plus SBRT
• Active Comparator: CBI
  Checkpoint blockade immunotherapy (CBI)
  Intervention: Drug: CBI

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 20, 2016): 146
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 2023
• Actual Primary Completion Date: August 16, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02843165
• Other Study ID Numbers: 151570
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Andrew Sharabi, University of California, San Diego
• Original Responsible Party: Same as current
• Current Study Sponsor: University of California, San Diego
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of California, San Diego
• Verification Date: May 2022