A Study of Hydroxychloroquine vs Placebo to Prevent COVID-19 Infection in Patients Receiving Radiotherapy

Study Overview
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Brief Summary
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The researchers are doing this study to find out whether the study drug hydroxychloroquine can prevent infection with the COVID-19 virus, compared with placebo, in people who are receiving radiation therapy for their cancer. The placebo used in this study is a tablet that looks the same as the study drug and is taken in the same way, but it does not contain any active ingredients.

Official Title
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A Phase II Randomized Double-Blind Placebo-Controlled Clinical Trial Of Hydroxychloroquine For Prophylaxis Against Covid-19 In Patients Receiving Radiotherapy (COVID)

Conditions
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COVID-19, Cancer

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Other: Placebo
* Radiation: Radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 ECOG 0-3 For patients who have not started radiation at the time of screening: patients are required to have a plan in place for a minimum of 10 radiation treatments with or without concurrent systemic therapy For patients who have already started radiation at the time of screening: patients must complete enrollment such that they are able to receive at least 10 radiation treatments with hydroxychloroquine. Disease Site Mandatory inclusion criteria: No COVID-19 symptoms within 14 days of enrollment: (Temp >38C in addition to sore throat, cough, wheezing, chest tightness, shortness of breath, body aches, chills, diarrhea, and anosmia) If symptoms are present within 14 days of enrollment, patients with a negative COVID-19 PCR or COVID-19 serology assay are eligible for inclusion. No close contact with confirmed COVID-19 person Close contact defined as: Within 6 feet for prolonged period Cohabitating Optional laboratory criteria (Recommended if available) Negative pre-treatment SARS-CoV-2 rapid antigen test result (within 1 week of enrollment) Negative pre-treatment SARS-CoV-2 PCR test result (within 1 week of enrollment) using MSKCC laboratory or outside laboratory assay Negative pre-treatment Standard Q COVID-19 IgM/IgG rapid serology result (within 1 week of enrollment) Blood serum for SARS-CoV-2 serology tests (being validated by MSKCC) Disease site meets following criteria: Head and Neck / High-Risk Skin Cancer Lung Cancer Breast Cancer Prostate Cancer Central Nervous System Tumors Gastrointestinal System Cancer Gynecologic cancer Other disease sites permitted at PI discretion Exclusion Criteria: Previous positive test for SARS-CoV-2 Previous positive serology test for SARS-CoV-2 Recent Chest CT meeting CT exclusion criteria Live in a skilled nursing facility with COVID-19 symptoms (Temp >38 C in addition to sore throat, cough, wheezing, chest tightness, shortness of breath, body aches or chills, diarrhea, anosmia) Known hypersensitivity to hydroxychloroquine or 4-aminoquinoline derivatives Pre-existing retinopathy Known chronic kidney disease, stage 4 or 5, or receiving dialysis Breast Feeding Tamoxifen Absolute neutrophil Count <1,000/ml at registration Concurrent use of any other quinine derivative Antiarrhythmic medications: amiodarone, sotalol, dofetilide, procainamide, quinidine, flecainide Glucose-6-phosphate dehydrogenase deficiency Pre-treatment corrected QT interval (QTc) ≥470 milliseconds** Prisoners Inability to participate Psoriasis History of suicidal ideation CT Criteria for Enrollment Exclusion (Optional - only for patients who received a diagnostic CT as part of standard of care or a thoracic CT as part of radiation simulation): All patients with COVID-19 typical radiographic findings on CT Chest as defined by the RSNA will be excluded. Patients with any NEW COVID-19 indeterminate radiographic findings on CT Chest that are concerning for COVID-19 will be excluded. COVID-19 indeterminate features are permitted if they can be demonstrated as STABLE on prior (>14 calendar days) CT Chest or PET/CT. If no prior comparison is available AND any intermediate or typical feature is present, the patient is not eligible. COVID-19 Atypical Features Isolated lobar or segmental consolidation without GGO Discrete small nodules (centrilobular, tree-in-bud) Lung cavitation Smooth interlobular septal thickening with pleural effusion COVID-19 Indeterminate Features Multifocal, diffuse, perihilar, or unilateral GGO with or without consolidation lacking a specific distribution and are non-rounded or non-peripheral Few very small GGO with a non-rounded and non-peripheral distribution COVID-19 Typical Features Peripheral, bilateral GGO with or without consolidation or visible intralobular lines (crazy paving) Multifocal GGO of rounded morphology with or without consolidation or visible intralobular lines (crazy paving) Reverse Halo sign or other findings of organizing pneumonia ** If pre-treatment QTC can be decreased to <470, the patient can be re-considered for trial.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a randomized (1:1), double-blind, placebo-controlled phase II clinical trial.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine<br>Every patient on trial must be scheduled to receive at least 10 radiation treatments prior to initiation of hydroxychloroquine 400mg daily. | Drug: Hydroxychloroquine<br>* 400mg daily<br>Radiation: Radiation therapy<br>* Standard radiation therapy will be prescribed and administered as per the patient's radiation oncologist.<br>|
| Placebo Comparator: Placebo<br>Every patient on trial must be scheduled to receive at least 10 radiation treatments prior to initiation of placebo 400mg daily. | Other: Placebo<br>* 400mg daily<br>Radiation: Radiation therapy<br>* Standard radiation therapy will be prescribed and administered as per the patient's radiation oncologist.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Incidence of SARS-CoV-2 Infection | Any patients who are enrolled and subsequently test positive for SARS-CoV-2 by RT-PCR (outside RT-PCR test results allowed) at any point during the 9 weeks following enrollment will be an event that is considered in the 9-week SARS-CoV-2 infection rate primary endpoint. | within 9 weeks from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Incidence of Severe COVID-19 or Death | Patients who are positive for SARS-CoV-2 (as defined above) who develop a new oxygen requirement attributable to COVID-19, tachypnea (RR > 20), or those who require hospitalization due to COVID-19 will be considered to have severe COVID-19. | within 12 weeks of randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hydroxychloroquine, Radiotherapy, 20-176