Intervention: Hydroxychloroquine
Trial phase: Phase 2
ATC code: P01BA02
SMILES: CCN(CCO)CCCC(C)Nc1ccnc2cc(Cl)ccc12
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 4
Group description: Every patient on trial must be scheduled to receive at least 10 radiation treatments prior to initiation of hydroxychloroquine 400mg daily.

Hydroxychloroquine: 400mg daily

Radiation therapy: Standard radiation therapy will be prescribed and administered as per the patient's radiation oncologist.
Eligibility criteria:
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.