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

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

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19; Cancer
• Intervention / Treatment: Drug: Hydroxychloroquine; Radiation: Radiation therapy; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memoral Sloan Kettering Basking Ridge (All Protocol Activities)
    • Middletown, New Jersey, United States, 07748
      • Memoral Sloan Kettering Monmouth (All Protocol Activities)
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen (All Protocol Activities)
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack (All protocol activities)
    • Harrison, New York, United States, 10604
      • Memoral Sloan Kettering Westchester (All protocol activities)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau (All Protocol Activities)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 7, 2020
• Primary Completion (ACTUAL): April 21, 2021
• Study Completion (ACTUAL): April 21, 2021

Study Registration Dates

• First Submitted: May 8, 2020
• First Submitted That Met QC Criteria: May 8, 2020
• First Posted (ACTUAL): May 11, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 27, 2021
• Last Update Submitted That Met QC Criteria: October 25, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Radiotherapy; Hydroxychloroquine; 20-176
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: 20-176

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No