A Study of Hydroxychloroquine vs Placebo to Prevent COVID-19 Infection in Patients Receiving Radiotherapy
Primary Purpose
COVID-19, Cancer
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hydroxychloroquine
Placebo
Radiation therapy
Sponsored by
About this trial
This is an interventional prevention trial for COVID-19 focused on measuring Hydroxychloroquine, Radiotherapy, 20-176
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.
Sites / Locations
- Memoral Sloan Kettering Basking Ridge (All Protocol Activities)
- Memoral Sloan Kettering Monmouth (All protocol activities)
- Memorial Sloan Kettering Bergen (All protocol Activities)
- Memorial Sloan Kettering Commack (All Protocol Activities)
- Memoral Sloan Kettering Westchester (All protocol activities)
- Memorial Sloan Kettering Cancer Center (All Protocol Activities)
- Memorial Sloan Kettering Nassau (All Protocol Activities)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Hydroxychloroquine
Placebo
Arm Description
Every patient on trial must be scheduled to receive at least 10 radiation treatments prior to initiation of hydroxychloroquine 400mg daily.
Every patient on trial must be scheduled to receive at least 10 radiation treatments prior to initiation of placebo 400mg daily.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT04381988
First Posted
May 8, 2020
Last Updated
October 25, 2021
Sponsor
Memorial Sloan Kettering Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT04381988
Brief Title
A Study of Hydroxychloroquine vs Placebo to Prevent COVID-19 Infection in Patients Receiving Radiotherapy
Official Title
A Phase II Randomized Double-Blind Placebo-Controlled Clinical Trial Of Hydroxychloroquine For Prophylaxis Against Covid-19 In Patients Receiving Radiotherapy (COVID)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated based results of other studies and use of the new vaccine.
Study Start Date
May 7, 2020 (Actual)
Primary Completion Date
April 21, 2021 (Actual)
Study Completion Date
April 21, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
4. Oversight
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
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, Cancer
Keywords
Hydroxychloroquine, Radiotherapy, 20-176
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This is a randomized (1:1), double-blind, placebo-controlled phase II clinical trial.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hydroxychloroquine
Arm Type
Experimental
Arm Description
Every patient on trial must be scheduled to receive at least 10 radiation treatments prior to initiation of hydroxychloroquine 400mg daily.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Every patient on trial must be scheduled to receive at least 10 radiation treatments prior to initiation of placebo 400mg daily.
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
400mg daily
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
400mg daily
Intervention Type
Radiation
Intervention Name(s)
Radiation therapy
Intervention Description
Standard radiation therapy will be prescribed and administered as per the patient's radiation oncologist.
Primary Outcome Measure Information:
Title
Cumulative Incidence of SARS-CoV-2 Infection
Description
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.
Time Frame
within 9 weeks from randomization
Secondary Outcome Measure Information:
Title
Cumulative Incidence of Severe COVID-19 or Death
Description
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.
Time Frame
within 12 weeks of randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nancy Lee, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memoral Sloan Kettering Basking Ridge (All Protocol Activities)
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Name
Memoral Sloan Kettering Monmouth (All protocol activities)
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
Memorial Sloan Kettering Bergen (All protocol Activities)
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Facility Name
Memorial Sloan Kettering Commack (All Protocol Activities)
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memoral Sloan Kettering Westchester (All protocol activities)
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Nassau (All Protocol Activities)
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center
Learn more about this trial
A Study of Hydroxychloroquine vs Placebo to Prevent COVID-19 Infection in Patients Receiving Radiotherapy
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