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Trial registered on ANZCTR


Registration number
ACTRN12620000842965
Ethics application status
Approved
Date submitted
20/08/2020
Date registered
26/08/2020
Date last updated
30/11/2023
Date data sharing statement initially provided
26/08/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
C-SMART.
COVID-19 Prevention and Treatment in Cancer.
Arm 2 : Post-exposure prevention in patients recently exposed to COVID-19
Scientific title
COVID-19 Prevention and Treatment in Cancer; a Sequential Multiple Assignment Randomised Trial; C-SMART study.
Arm 2: Effect of daily Interferon-alpha on cancer patients with known positive contact with COVID-19.
Secondary ID [1] 302085 0
nil known
Universal Trial Number (UTN)
U1111-1256-8488
Trial acronym
C-SMART (Arm 2)
Linked study record
ARM 1 ACTRN12620000843954
ARM 3 ACTRN12620000841976
ARM 4 ACTRN12620000844943

Health condition
Health condition(s) or problem(s) studied:
COVID-19 318694 0
Cancer 318695 0
Condition category
Condition code
Infection 316708 316708 0 0
Other infectious diseases
Cancer 316709 316709 0 0
Any cancer
Respiratory 316764 316764 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ARM 2 - Post Exposure Prophylaxis
Drug: IFN-a
Dose: 1,000,000 IU/Daily
Duration: 7 days
Mode: Intranasal spray (self administered)
Adherence: drug return logs and patient reported.

Description of study design:
This SMART design specifies that participants entering the trial who have had no known COVID-19 exposure are initially randomised to either low-dose intranasal IFN-a or placebo as pre-exposure prophylaxis against developing COVID-19. Any participants who have a known COVID-19 exposure are randomised to high-dose IFN-a or placebo as a post-exposure prophylaxis against developing COVID-19. If, at any stage after enrolling, a participant develops ‘moderate’ COVID-19, then they are then randomised to either selinexor or placebo, and if at any stage after enrolling the participant develops ‘severe’ COVID-19 they are then randomised to either lenzilumab or placebo.
Importantly, participants enrolling into the trial can directly enter any of the four interventions if they meet the appropriate entry criteria.
Intervention code [1] 318382 0
Prevention
Intervention code [2] 318383 0
Treatment: Drugs
Comparator / control treatment
Matching placebo. (normal saline intranasal spray
Control group
Placebo

Outcomes
Primary outcome [1] 324847 0
ARM 2: Coprimary outcome 1
incidence of COVID-19 when Interferon alpha is given as post-exposure prophylaxis with a known positive contact or exposure with COVID-19. COVID-19 confirmed by qPCR from respiratory swab .
Timepoint [1] 324847 0
28 days from baseline
Primary outcome [2] 324848 0
ARM 2: Coprimary outcome 2.
incidence of any upper or lower community acquired respiratory viral infection (define as identification of respiratory viruses such as coronavirus other than SARS-CoV-2, influenza, parainfluenza, respiratory syncytial virus, rhinovirus, adenovirus, human metapneumovirus).
Assessed using local standard of care testing (e.g. respiratory swabs, saliva and/or blood)
Timepoint [2] 324848 0
28 days from baseline
Secondary outcome [1] 385903 0
ARM 2: secondary outcome 1
Duration of acute respiratory symptoms in case of confirmed COVID-19 diagnosed during the study period (days).
assessed using a take-home PRO specifically developed and approved for this study entitled "patient symptom Diary". in combination with any relevant medical records.
Timepoint [1] 385903 0
28 days from baseline
Secondary outcome [2] 385904 0
ARM 2: secondary outcome 2
Time to diagnosis of COVID-19 in case of confirmed COVID-19 diagnosed during the study period (days). assessed using medical records
Timepoint [2] 385904 0
28 days from baseline
Secondary outcome [3] 385905 0
ARM 2: secondary outcome 3
Illness severity in case of confirmed COVID-19 diagnosed during the study period, defined as the maximal score on the World Health Organization (WHO)’s clinical progression ordinal scale ranging from 0 (uninfected) to 10 (death)
Timepoint [3] 385905 0
28 days from baseline
Secondary outcome [4] 385906 0
ARM 2: secondary outcome 4
Incidence of unplanned all-cause hospital admission during the study period. assessed using medical records.
Timepoint [4] 385906 0
28 days from baseline
Secondary outcome [5] 385907 0
ARM 2: secondary outcome 5
Incidence of unplanned infection-related hospital admission during the study period. assessed using medical records
Timepoint [5] 385907 0
28 days from baseline
Secondary outcome [6] 385908 0
ARM 2: secondary outcome 6
Incidence of seroconversion of SARS-CoV-2 at the end of the study period. assessed using qPCR.
Timepoint [6] 385908 0
28 days from baseline
Secondary outcome [7] 385909 0
ARM 2: secondary outcome 7
Incidence of testing for COVID-19 during the study period.
Composite measure: frequency of testing if outcome is met. assessed using medical records
Timepoint [7] 385909 0
28 days from baseline

Eligibility
Key inclusion criteria
ARM 2
1. Age equal to or greater than 18 years old.
2. Any haematological or solid tumour
3. Current or within the last 12 months received cancer related treatment such as chemotherapy, radiotherapy or targeted small molecule, cellular therapy or immune-modulating therapy
4. Signed written and verbal informed consent
5. Have been exposed to a known COVID-19 case within the last 72 hours, defined by the current Department of Health and Human services such as household contact, 15 minutes of face to face exposure, 2 hours in close space.
6. Willingness to inform the study nurse/co-ordinator of COVID-19 testing
7. Willingness to perform a self-collect nose/throat swab
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
ARM 2
1. Previous diagnosis of COVID-19 (microbiologically proven, either symptomatic or asymptomatic)
2. Any contra-indication to intra-nasal IFN-a such as severe nasal bleeding requiring intervention, nasal malignancy, nasal deformity, radiotherapy to the nasopharynx and/or oropharynx
3. Pregnant or breast-feeding women, or women who wish to become pregnant during the course of the study
4. Patient unable to return for follow-up
5. Life expectancy of less than 1 month
6. Patient already included in another intervention study on the prevention of COVID-19
7. Currently unwell with influenza-like symptoms

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
simple randomisation using computer software with stratification based on age (above and below 65 years old)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
sequential multiple assignment randomisation trial
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
By employing an Bayesian approach for directly inferring the probabilities of efficacy for each of the interventions proposed, the trial sample size is not required to be fixed in advance, which is of benefit given there is limited information required to derive expected sample size. However, we have provided an indicative sample size that would be required to identify a treatment effect for each primary hypothesis if using a more conventional, non-Bayesian approach. The expected sample sizes for each treatment arm (1:1 randomisation) are provided in the summary table and were calculated for 90% power and a 5% two-sided level of significance

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Safety concerns
Date of first participant enrolment
Anticipated
1/09/2020
Actual
Date of last participant enrolment
Anticipated
1/09/2021
Actual
Date of last data collection
Anticipated
1/12/2021
Actual
Sample size
Target
170
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 17285 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 17286 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 17287 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 17288 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [5] 17289 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 31005 0
3000 - Melbourne
Recruitment postcode(s) [2] 31006 0
3050 - Parkville
Recruitment postcode(s) [3] 31007 0
3084 - Heidelberg
Recruitment postcode(s) [4] 31008 0
3065 - Fitzroy
Recruitment postcode(s) [5] 31009 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 306506 0
Government body
Name [1] 306506 0
Australian Government. Medical Research Future Fund
Country [1] 306506 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan Street.
Melbourne, Victoria
3000
Country
Australia
Secondary sponsor category [1] 307033 0
None
Name [1] 307033 0
Address [1] 307033 0
Country [1] 307033 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306708 0
Peter MacCallum HREC
Ethics committee address [1] 306708 0
Ethics committee country [1] 306708 0
Australia
Date submitted for ethics approval [1] 306708 0
13/07/2020
Approval date [1] 306708 0
21/08/2020
Ethics approval number [1] 306708 0
HREC/65954/PMCC

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104746 0
Prof Monica Slavin
Address 104746 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne
Vic
3000
Country 104746 0
Australia
Phone 104746 0
+61 3 8559 7997
Fax 104746 0
Email 104746 0
[email protected]
Contact person for public queries
Name 104747 0
Ronan Burder
Address 104747 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne
Victoria
3000
Country 104747 0
Australia
Phone 104747 0
+61 3 8559 5000
Fax 104747 0
Email 104747 0
[email protected]
Contact person for scientific queries
Name 104748 0
Michelle Yong
Address 104748 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne
Victoria
3000
Country 104748 0
Australia
Phone 104748 0
+61 3 8559 5000
Fax 104748 0
Email 104748 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.