Lung Irradiation for COVID-19 Pneumonia

Study Overview
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Brief Summary
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In this research study the investigators want to learn more about the potential benefit of radiation to the lung to improve the health of patients who are hospitalized with Coronavirus-19 (COVID-19) due to infection with a virus called SARS-CoV-2. This infection causes inflammation of the lung, which can make it difficult to breathe. As a result, patients may need supplemental oxygen or be placed on a ventilator. The investigators believe that low dose radiation therapy to the lung may reduce this inflammation and increase the likelihood that patients will need less oxygen support such as ventilation or supplemental oxygen, or be discharged from the hospital in fewer days, compared to without radiation therapy. The amount of radiation is much lower than what is typically used to treat other conditions such as cancer, although it is higher than the dose used for routine medical imaging.

Official Title
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Pilot Study of Low-Dose Single or Bilateral Whole Lung Irradiation for SARS-CoV-2 Pneumonia

Conditions
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SARS-CoV 2

Intervention / Treatment
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* Radiation: Phase 1
* Radiation: Phase 1
* Radiation: Phase 2
* Radiation: Phase 2
* Radiation: Phase 2


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Diagnosis of SARS-CoV-2 infection by RT-PCR or another approved laboratory test ≤ 3 days before enrollment or ≤ 14 days before enrollment with progressive disease suggestive of ongoing SARS-CoV-2 infection; retesting allowed Current hospitalization for ≤ 14 days with SARS-CoV-2 infection at the time of enrollment Use of supplemental oxygen or oxygen saturation ≤ 94% on room air Age ≥ 40 May receive antiviral medication (e.g., remdesivir, lopinavir/ritonavir, oseltamivir, favipiravir), antibiotics (e.g., azithromycin), chloroquine, hydroxychloroquine, corticosteroids, statins, anticoagulation, antiplatelet agents (e.g., aspirin) and/or convalescent plasma from recovered individuals off study and/or on study if permitted by the other protocol Exclusion criteria Prior or planned treatment with interleukin inhibitors (e.g., tocilizumab, canakinumab, sarilumab) or TNF-α inhibitors within 14 days of enrollment Prior lobectomy or pneumonectomy Prior thoracic radiotherapy with cumulative lung V20 > 15% to either lung within 1 year of enrollment, or any radiotherapy resulting in a maximum lung dose of 100 cGy or higher within 14 days of enrollment Prior chemotherapy or other systemic therapy with potential for pulmonary toxicity or radiosensitization within 14 days or 5 half-lives, whichever is greater, of enrollment, e.g., bleomycin or gemcitabine Prior cancer immunotherapy with an immune checkpoint inhibitor within 60 days of enrollment Severe pre-existing heart disease, e.g., New York Heart Association (NYHA) functional class ≥ 3 congestive heart failure History of bone marrow or solid organ transplantation Known history of autoimmune collagen vascular disease, e.g., scleroderma Known hereditary syndrome with increased sensitivity to ionizing radiation, e.g., ataxia-telangiectasia or Fanconi anemia Pregnancy Inability to be positioned supine and flat for radiation planning and delivery Inability to provide informed consent or lack of an authorized representative who can provide informed consent

Ages Eligible for Study
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Minimum Age: 40 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: No irradiation<br> | Radiation: Phase 2<br>* Arm A - No irradiation<br>|
| Experimental: 100 cGy single lung irradiation<br>100 cGy single lung radiation | Radiation: Phase 1<br>* Dose Level 1 - 100 cGy irradiation to a single (right-sided) lung using 6 MV photons delivered using a clinical linear accelerator<br>Radiation: Phase 2<br>* Arm B - 100 cGy irradiation to a single (right-sided) lung using 6 MV photons delivered using a clinical linear accelerator<br>|
| Experimental: 100 cGy bilateral lung irradiation<br>100 cGy bilateral lung radiation | Radiation: Phase 1<br>* Dose Level 2 - 100 cGy irradiation to both lungs using 6 MV photons delivered using a clinical linear accelerator<br>Radiation: Phase 2<br>* Arm C - 100 cGy irradiation to both lungs using 6 MV photons delivered using a clinical linear accelerator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Feasibility and safety of treating hospitalized patients with SARS-CoV-2 pneumonia with single or bilateral whole lung irradiation | Subjects will be treated with 100 cGy irradiation to a single (right-sided) lung (dose level 1) or 100 cGy irradiation to both lungs (dose level 2) following a 3 + 3 dose escalation scheme | 4 days after randomization | 
| Phase 2: Proportion with clinical improvement on a 7-point ordinal scale on day 4 after randomization | The ordinal scale is an assessment of the clinical status on a given day. Each day, the worst (lowest) score from the previous day will be recorded as the score for that previous day. The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring low flow supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care Not hospitalized | 4 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement or worsening on the 7-point ordinal scale over additional intervals |  | Up to 30 days after randomization | 
| Rate and duration of use of supplemental oxygen |  | Up to 30 days after randomization | 
| Rate and duration of fever > 38ºC |  | Up to 30 days after randomization | 
| Rate and duration of invasive mechanical ventilation |  | Up to 30 days after randomization | 
| Duration of hospitalization |  | Up to 30 days after randomization | 
| Proportion of participants with overall survival up to 30 days after randomization |  | Up to 30 days after randomization | 
| Improvement in radiographic findings related to infection/inflammation; comparisons include on study versus baseline scans and irradiated vs. unirradiated lung in subjects randomized to receive single lung irradiation |  | Up to 30 days after randomization | 
| Treatment-emergent adverse events |  | Up to 30 days after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, Radiation Therapy, COVID-19