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

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT04381988
• Collaborator: (none)
• Enrollment: 4
• Locations: 7
• Arms: 2
• Actual Duration (Months): 11.5
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19; Cancer	Drug: Hydroxychloroquine; Other: Placebo; Radiation: Radiation therapy	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a randomized (1:1), double-blind, placebo-controlled phase II clinical trial.This is a randomized (1:1), double-blind, placebo-controlled phase II clinical trial.
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase II Randomized Double-Blind Placebo-Controlled Clinical Trial Of Hydroxychloroquine For Prophylaxis Against Covid-19 In Patients Receiving Radiotherapy (COVID)
• Actual Study Start Date: May 7, 2020
• Actual Primary Completion Date: Apr 21, 2021
• Actual Study Completion Date: Apr 21, 2021

Arms and Interventions

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.	Other: Placebo; 400mg daily; Radiation: Radiation therapy; Standard radiation therapy will be prescribed and administered as per the patient's radiation oncologist.

Outcome Measures

Primary Outcome Measures

1. Cumulative Incidence of SARS-CoV-2 Infection [within 9 weeks from randomization]

   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

1. Cumulative Incidence of Severe COVID-19 or Death [within 12 weeks of randomization]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memoral Sloan Kettering Basking Ridge (All Protocol Activities)	Basking Ridge	New Jersey	United States	07920
2	Memoral Sloan Kettering Monmouth (All protocol activities)	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen (All protocol Activities)	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Commack (All Protocol Activities)	Commack	New York	United States	11725
5	Memoral Sloan Kettering Westchester (All protocol activities)	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center (All Protocol Activities)	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau (All Protocol Activities)	Uniondale	New York	United States	11553

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Nancy Lee, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 7, 2020

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT04381988
• Other Study ID Numbers: 20-176
• First Posted: May 11, 2020
• Last Update Posted: Oct 27, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Keywords provided by Memorial Sloan Kettering Cancer Center: Hydroxychloroquine; Radiotherapy; 20-176
• Additional relevant MeSH terms: COVID-19; Hydroxychloroquine

Study Results

Participant Flow

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/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.	Every patient on trial must be scheduled to receive at least 10 radiation treatments prior to initiation of placebo 400mg daily. Placebo: 400mg daily Radiation therapy: Standard radiation therapy will be prescribed and administered as per the patient's radiation oncologist.
Period Title: Overall Study
STARTED	4	0
COMPLETED	0	0
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Hydroxychloroquine	Placebo	Total
Arm/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.	Every patient on trial must be scheduled to receive at least 10 radiation treatments prior to initiation of placebo 400mg daily. Placebo: 400mg daily Radiation therapy: Standard radiation therapy will be prescribed and administered as per the patient's radiation oncologist.	Total of all reporting groups
Overall Participants	4	0	4
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	63	63
Sex: Female, Male (Count of Participants)
Female	3 75%	0 NaN	3 75%
Male	1 25%	0 NaN	1 25%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 NaN	0 0%
Not Hispanic or Latino	4 100%	0 NaN	4 100%
Unknown or Not Reported	0 0%	0 NaN	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 NaN	0 0%
Asian	0 0%	0 NaN	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 NaN	0 0%
Black or African American	0 0%	0 NaN	0 0%
White	4 100%	0 NaN	4 100%
More than one race	0 0%	0 NaN	0 0%
Unknown or Not Reported	0 0%	0 NaN	0 0%
Region of Enrollment (Count of Participants)
United States	4 100%	0 NaN	4 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Data were not collected.

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/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.	Every patient on trial must be scheduled to receive at least 10 radiation treatments prior to initiation of placebo 400mg daily. Placebo: 400mg daily Radiation therapy: Standard radiation therapy will be prescribed and administered as per the patient's radiation oncologist.
Measure Participants	0	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Hydroxychloroquine	Placebo
Arm/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.	Every patient on trial must be scheduled to receive at least 10 radiation treatments prior to initiation of placebo 400mg daily. Placebo: 400mg daily Radiation therapy: Standard radiation therapy will be prescribed and administered as per the patient's radiation oncologist.
Measure Participants	0	0

Adverse Events

Time Frame	Up to 6 months
Adverse Event Reporting Description	The study was terminated based results of other studies and use of the new vaccine
Arm/Group Title	Hydroxychloroquine		Placebo
Arm/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.		Every patient on trial must be scheduled to receive at least 10 radiation treatments prior to initiation of placebo 400mg daily. Placebo: 400mg daily Radiation therapy: Standard radiation therapy will be prescribed and administered as per the patient's radiation oncologist.
All Cause Mortality
	Hydroxychloroquine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/0 (NaN)
Serious Adverse Events
	Hydroxychloroquine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Hydroxychloroquine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.