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

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.