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Trial registered on ANZCTR


Registration number
ACTRN12620000843954
Ethics application status
Approved
Date submitted
20/08/2020
Date registered
26/08/2020
Date last updated
26/08/2020
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 1 : Prevention in patients not infected with COVID-19.
Scientific title
COVID-19 Prevention and Treatment in Cancer; a Sequential Multiple Assignment Randomised Trial; C-SMART study. Arm 1: Effect of daily Interferon-alpha on cancer patients without known positive contact with COVID-19.
Secondary ID [1] 302028 0
nil known
Universal Trial Number (UTN)
U1111-1256-8488
Trial acronym
C-SMART (Arm 1)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 318605 0
Cancer 318606 0
Condition category
Condition code
Infection 316624 316624 0 0
Other infectious diseases
Cancer 316625 316625 0 0
Any cancer
Respiratory 316754 316754 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ARM 1 - Prophylaxis
Drug: IFN-a
Dose: 40,000 IU/Daily
Duration: 3 months
Mode: Intranasal spray (self administered)
Adherence: drug return logs, 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] 318327 0
Prevention
Comparator / control treatment
Matching placebo. (normal saline intranasal spray)
Control group
Placebo

Outcomes
Primary outcome [1] 324750 0
ARM 1: Coprimary outcome 1
Incidence of COVID-19 in cancer patients using interferon-alpha as prophylaxis without known positive contact with COVID-19.
COVID-19 confirmed by qPCR from respiratory swab .
Timepoint [1] 324750 0
3 months from baseline.
Primary outcome [2] 324853 0
ARM 1: 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] 324853 0
3 months from baseline.
Secondary outcome [1] 385636 0
ARM 1, secondary endpoint 1
Duration of acute respiratory/ILI symptoms in case of confirmed respiratory infection during the study period. (composite either COVID-19 or other respiratory viral infection).
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] 385636 0
120 days from baseline
Secondary outcome [2] 385637 0
ARM 1, secondary endpoint 2
Time to diagnosis of COVID-19 in case of confirmed COVID-19 diagnosed during the study period (days). Assessed using patient medical records
Timepoint [2] 385637 0
120 days from baseline
Secondary outcome [3] 385638 0
ARM 1, secondary endpoint 3
Time to diagnosis of other respiratory viral infection in case of confirmed other respiratory viral infection diagnosed during the study period (days). assessed using patient medical records
Timepoint [3] 385638 0
120 days from baseline
Secondary outcome [4] 385639 0
ARM 1, secondary endpoint 4
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 scale ranging from 0 (uninfected) to 10 (death)
Timepoint [4] 385639 0
120 days from baseline
Secondary outcome [5] 385640 0
ARM 1, secondary endpoint 5
Incidence of unplanned all-cause hospital admission during the study period.
Composite measure: duration of hospital stay if outcome met. assessed using medical records
Timepoint [5] 385640 0
120 days from baseline
Secondary outcome [6] 385641 0
ARM 1, secondary endpoint 6
Incidence of unplanned infection-related hospital admission during the study period. Composite measure: duration of hospital stay if outcome met. assessed using medical records
Timepoint [6] 385641 0
120 days from baseline
Secondary outcome [7] 385642 0
ARM 1, secondary endpoint 7
Incidence of sero-conversion of SARS-CoV-2 at the end of the study period. assessed using qPCR
Timepoint [7] 385642 0
120 days from baseline
Secondary outcome [8] 385643 0
ARM 1, secondary endpoint 8
Incidence of death from any cause during the study period. assessed using patient medical records
Timepoint [8] 385643 0
120 days from baseline
Secondary outcome [9] 385644 0
ARM 1, secondary endpoint 9
Incidence of testing for COVID-19 during the study period.
Composite measure: frequency of testing if outcome is met. assessed using medical records
Timepoint [9] 385644 0
120 days from baseline

Eligibility
Key inclusion criteria
ARM 1:
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. Willingness to inform the study nurse/co-ordinator of COVID-19 testing
6. Willingness to perform a self-collect nose/throat swab
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
ARM 1
1. Previous diagnosis of COVID-19 (microbiologically proven, either symptomatic or asymptomatic)
2. 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.
3. 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
4. Pregnant or breast-feeding women, or women who wish to become pregnant during the course of the study
5. Participant unable to return for regular follow-up
6. Life expectancy of less than 4 months
7. Participant already included in another intervention study on the prevention of COVID-19
8. Currently unwell with influenza-like symptoms – if participant is found to be COVID-19 negative and becomes asymptomatic, they can be reconsidered for participation

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
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 17253 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 17254 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 17255 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 17257 0
Westmead Hospital - Westmead
Recruitment hospital [5] 17290 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 30969 0
2145 - Westmead
Recruitment postcode(s) [2] 30965 0
3000 - Melbourne
Recruitment postcode(s) [3] 30966 0
3050 - Parkville
Recruitment postcode(s) [4] 31010 0
3065 - Fitzroy
Recruitment postcode(s) [5] 30967 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 306450 0
Government body
Name [1] 306450 0
Australian Government. Medical Research Future Fund
Address [1] 306450 0
Australian Government Department of Health Victorian Office
Level 8/595 Collins St, Melbourne VIC 3000
Country [1] 306450 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan Street.
Melbourne, Victoria
3000
Country
Australia
Secondary sponsor category [1] 306967 0
None
Name [1] 306967 0
Address [1] 306967 0
Country [1] 306967 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306656 0
Peter MacCallum HREC
Ethics committee address [1] 306656 0
305 Grattan Street.
Melbourne
Victoria 3000
Ethics committee country [1] 306656 0
Australia
Date submitted for ethics approval [1] 306656 0
13/07/2020
Approval date [1] 306656 0
21/08/2020
Ethics approval number [1] 306656 0
HREC/65954/PMCC

Summary
Brief summary
A multi-centre Australian trial with four arms aims to evaluate several different immune modulating drugs for prevention and treatment of COVID-19 specifically in the cancer population. This study arm (arm 1) is evaluating the effect of interferon-alpha on the incidence of COVID-19 infection in cancer patients with no COVID-19 infection or no known COVID-19 positive contacts.

Who is it for?
You may be eligible to join this study arm if you are aged 18 and above, have any haematological or solid tumour, currently receiving cancer-related treatment, have a negative COVID-19 test and without known positive contact with COVID-19

Study details
Participants in this study arm are randomly allocated (by chance) to one of two groups. One group will receive daily interferon-alpha intransal spray for 3 months while the other group will receive a daily placebo intranasal spray for 3 months.

Participants will be followed during the 3-month treatment for incidence of COVID-19 and other respiratory infections.

This study is one arm of a four arm, sequential multiple assignment randomisation trial where participants may become eligible and transition to different arms and treatments if they become exposed to COVID-19 or are hospitalised with an active moderate/severe COVID-19 infection.

It is hoped this research will provide insight into the best practice for prevention and treatment COVID-19 in cancer patients as emerging standard of care measures are not always suitable to this especially vulnerable population.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 104578 0
Prof Monica Slavin
Address 104578 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne
Vic
3000
Country 104578 0
Australia
Phone 104578 0
+61 3 8559 7997
Fax 104578 0
Email 104578 0
monica.slavin@petermac.org
Contact person for public queries
Name 104579 0
Mr Ronan Burder
Address 104579 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne
Victoria
3000
Country 104579 0
Australia
Phone 104579 0
+61 3 8559 5000
Fax 104579 0
Email 104579 0
ronan.burder@petermac.org
Contact person for scientific queries
Name 104580 0
Dr Michelle Yong
Address 104580 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne
Victoria
3000
Country 104580 0
Australia
Phone 104580 0
+61 3 8559 5000
Fax 104580 0
Email 104580 0
michelle.yong@petermac.org

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 other documents available
Summary results
No Results