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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Metastatic Cancer

Intervention / Treatment
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* Drug: Checkpoint blockade immunotherapy
* Radiation: Checkpoint blockade immunotherapy plus SBRT


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | Complete response plus partial response | Responses measured by RECIST at 16 weeks from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stereotactic body radiation therapy, checkpoint blockade immunotherapy