A Study of Hydroxychloroquine versus Placebo to Prevent COVID-19 Infection in Patients Receiving Radiation Therapy
This phase II trial studies how well hydroxychloroquine works in preventing infection with the COVID-19 virus in patients receiving radiation therapy. Hydroxychloroquine has been approved for the prevention and treatment of malaria, and the treatment of lupus and rheumatoid arthritis. Receiving radiation therapy may increase the risk of infection with the COVID-19 virus because the patients are in frequent and close contact with healthcare workers and with other patients who may have become infected. Patients receiving treatment for cancer may also have weakened immune system. Giving hydroxychloroquine may help prevent infection with SARS-CoV-2 in patients who are receiving radiation therapy for their cancer.
Inclusion Criteria
- Eastern Cooperative Oncology Group (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
- No COVID-19 symptoms within 14 days of enrollment: * (Temperature [temp] > 38 Celsius [C] 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 polymerase chain reaction (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 principal investigator (PI) discretion
Exclusion Criteria
- Previous positive test for SARS-CoV-2
- Previous positive serology test for SARS-CoV-2
- Recent chest computed tomography (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 * If pre-treatment QTC can be decreased to < 470, the patient can be re-considered for trial
- 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 Radiological Society of North America (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 ground glass opacity (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
Additional locations may be listed on ClinicalTrials.gov for NCT04381988.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To compare the cumulative incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 9 weeks from randomization in patients receiving radiotherapy with prophylactic hydroxychloroquine versus placebo.
SECONDARY OBJECTIVES:
I. To compare the cumulative incidence of severe coronavirus disease 2019 (COVID-19) or death within 12 weeks of randomization in patients receiving radiotherapy with prophylactic hydroxychloroquine versus placebo.
II. To compare the cumulative incidence of symptomatic COVID-19 within 9 weeks of randomization in patients receiving radiotherapy with prophylactic hydroxychloroquine versus (vs) placebo.
III. To compare the cumulative incidence of acute grade >= 3 toxicity in patients receiving radiotherapy with prophylactic hydroxychloroquine versus placebo within 12 weeks of randomization.
CORRELATIVE STUDIES OBJECTIVES:
I. To evaluate the baseline prevalence of anti-SARS-CoV-2 antibodies in patients receiving radiation and chemoradiation without history of symptomatic COVID-19.
II. To correlate the qualitative Standard Q COVID-19 immunoglobulin (Ig)M/IgG rapid immunochromatographic test manufactured by SD Biosensor with quantitative SARS-CoV-2 serology tests (assays being validated in Memorial Sloan Kettering Cancer Center [MSKCC] Laboratory Medicine) in patients where banked serology is available.
III. To correlate the rapid Standard COVID-19 Ag test manufactured by SD Biosensor and distributed to us for the trial by Henry Schein Inc. with the SARS-Co-V-2 reverse transcriptase polymerase chain reaction (RT PCR), only in patients where RT-PCR data is available.
IV. In patients who are serology negative, to compare the cumulative incidence of symptomatic COVID-19 within 9 weeks from randomization to prophylactic hydroxychloroquine versus placebo.
V. In patients who are serology negative, to compare the cumulative incidence of severe COVID-19 within 12 weeks from randomization to prophylactic hydroxychloroquine versus placebo.
VI. Collected serum will be stored for future studies.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients undergo standard of care radiation therapy and receive hydroxychloroquine orally (PO) daily during treatment. Patients then receive hydroxychloroquine orally (PO) daily for 14 days in the absence of disease progression or unacceptable toxicity.
GROUP II: Patients undergo standard of care radiation therapy and receive placebo PO daily during treatment. Patients then receive placebo PO daily for 14 days in the absence of disease progression or unacceptable toxicity.
After completion of randomization, patients are followed up for 12 weeks.
Trial PhasePhase II
Trial Typeprevention
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorNancy Y. Lee
- Primary ID20-176
- Secondary IDsNCI-2020-03533
- ClinicalTrials.gov IDNCT04381988