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Trial registered on ANZCTR


Registration number
ACTRN12620000841976
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 3: treatment among cancer patients with moderate COVID-19 infection.
Scientific title
COVID-19 Prevention and Treatment in Cancer; a Sequential Multiple Assignment Randomised Trial; C-SMART study.
Arm 3: Effect of selinexor in cancer patients with moderate COVID-19 infection.
Secondary ID [1] 302086 0
nil known
Universal Trial Number (UTN)
U1111-1256-8488
Trial acronym
C-SMART (Arm 3)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 318696 0
Cancer 318697 0
Condition category
Condition code
Infection 316710 316710 0 0
Other infectious diseases
Cancer 316711 316711 0 0
Any cancer
Respiratory 316765 316765 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ARM 3 - Moderate COVID-19 infection
Drug: Selinexor
Dose: 20mg 3x weekly
Duration: 14 days
Mode: oral - self administered tablet
adherence: supervised administration while inpatient. self 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] 318384 0
Treatment: Drugs
Comparator / control treatment
placebo controlled. exact matching tablet. Information about the specific formulation is pending, manufactured by Karyopharm (who also produce the IP)
Control group
Placebo

Outcomes
Primary outcome [1] 324849 0
ARM 3 Primary outcome.
composite outcome: incidence of death and/or need for invasive or non-invasive ventilation.
assessed using medical records
Timepoint [1] 324849 0
60 days from baseline
Secondary outcome [1] 385913 0
ARM 3: secondary outcome 1
Time to clinical improvement defined as
a. Resolution of fever – oral temperature < 38oC for 24 hours without antipyretics AND
b. Respiratory rate < 20 breaths/minute OR
c. Oxygen saturation > 94% on room air OR
d. Hospital discharge

assessed using medical recods
Timepoint [1] 385913 0
60 days from baseline
Secondary outcome [2] 385914 0
ARM 3: secondary outcome 2
Illness severity of COVID-19, defined as the maximal score on the World Health Organization (WHO)’s clinical progression ordinal scale ranging from 0 (uninfected) to 10 (death)
Timepoint [2] 385914 0
60 days from baseline
Secondary outcome [3] 385915 0
ARM 3: secondary outcome 3
change to clinical condition assessed with Karnofsky Performance score
Timepoint [3] 385915 0
60 days from baseline
Secondary outcome [4] 385916 0
ARM 3: secondary outcome 4
Time to progression to severe COVID-19, defined by WHO ordinal scale
Timepoint [4] 385916 0
60 days from baseline
Secondary outcome [5] 385917 0
ARM 3: secondary outcome 5
Time to all-cause mortality
Timepoint [5] 385917 0
60 days from baseline
Secondary outcome [6] 385918 0
ARM 3: secondary outcome 6
Duration of hospitalisation.
assessed using medical records
Timepoint [6] 385918 0
at discharge
Secondary outcome [7] 385919 0
ARM 3: secondary outcome 7
Duration of COVID-19 symptoms (symptoms include: headache, general aches & pain, fatigue, weakness, nasal stuffiness, nasal drainage, sore throat, cough, loss of sense of smell, chest discomfort, chills, fever, other as relevant)
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 [7] 385919 0
60 days from baseline
Secondary outcome [8] 385920 0
ARM 3: secondary outcome 8
Duration of oxygen supplementation (days). assessed using medical records.
Timepoint [8] 385920 0
60 days from baseline
Secondary outcome [9] 385921 0
ARM 3: secondary outcome 9
change in nasopharyngeal SARS-CoV-2 viral load shedding (assessed via qPCR)
Timepoint [9] 385921 0
60 days from baseline
Secondary outcome [10] 385922 0
ARM 3: secondary outcome 10
Safety and tolerability of selinexor defined as listing and documentation of frequency and severity of adverse effects. examples of some known possible adverse events include (but are not limited to):
• nausea
• vomiting
• diarrhoea
• weight loss
• constipation
• fatigue and asthenia – loss of energy; weakness
• decreased appetite
• dehydration
• abdominal pain
• dysgeusia – change in taste
• shortness of breath
• cough
• dizziness
• fever
• blurred vision
• headache
• difficulty falling asleep

Outcome assessed using any/all of medical records, patient reported, vital signs, ECG, imaging, other investigative procedure as per standard local practice.
Timepoint [10] 385922 0
60 days from baseline
Secondary outcome [11] 385923 0
ARM 3: secondary outcome 11
composite outcome: incidence of changes in blood results relevant to clinical improvement.
a. Changes in C-reactive protein (CRP)
b. Changes in ferritin level
c. Changes in lactate dehydrogenase (LDH) level
Timepoint [11] 385923 0
60 days from baseline

Eligibility
Key inclusion criteria
ARM 3
1. Age equal to or greater than 18 years of age.
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. Laboratory confirmation of SARS-CoV-2 by PCR as per local laboratory assays
6. Hospitalised
7. Symptoms of COVID-19 such as:
a. Fever equal to or greater than 38 degrees Celsius OR
b. Tachypnoea respiratory rate equal to or greater than 20 breaths/min OR
c. Pulse Oxygen saturation (SpO2) equal to or less than 94%
8. Concurrent standard of care antimicrobials, antivirals are allowed.
9. Female and male patients of child bearing potential will use highly effective contraception. In female child bearing potential participants a negative urine pregnancy test will be required.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
ARM 3
1. Unable to take oral medication
2. Any known allergic reactions to selinexor or concomitant medication-related contra-indications to selinexor.
3. Severe critical COVID-19 infection defined as:
a) Requiring invasive or non-invasive mechanical ventilation, ECMO
b) Anticipated unlikely to survive within 48 hours
4. In the opinion of the investigator and primary oncologist, participation in the study would not be in the best interests of the participant
5. Severe renal impairment defined as creatinine clearance (CrCL) < 20ml/min as calculated using the Cockcroft Gault formula
6. Severe hepatic impairment defined as aspartate transaminase (AST) or alanine transaminase (ALT) > 5 x upper limit of normal (ULN)

Study design
Purpose of the study
Treatment
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)
Safety/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] 17291 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 17292 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 17293 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 17294 0
Westmead Hospital - Westmead
Recruitment hospital [5] 17295 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 31014 0
2145 - Westmead
Recruitment postcode(s) [2] 31011 0
3000 - Melbourne
Recruitment postcode(s) [3] 31012 0
3050 - Parkville
Recruitment postcode(s) [4] 31015 0
3065 - Fitzroy
Recruitment postcode(s) [5] 31013 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 306507 0
Government body
Name [1] 306507 0
Australian Government. Medical Research Future Fund
Address [1] 306507 0
Australian Government Department of Health Victorian Office
Level 8/595 Collins St, Melbourne VIC 3000
Country [1] 306507 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan Street.
Melbourne, Victoria
3000
Country
Australia
Secondary sponsor category [1] 307034 0
None
Name [1] 307034 0
Address [1] 307034 0
Country [1] 307034 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306709 0
Peter MacCallum HREC
Ethics committee address [1] 306709 0
305 Grattan Street.
Melbourne
Victoria 3000
Ethics committee country [1] 306709 0
Australia
Date submitted for ethics approval [1] 306709 0
13/07/2020
Approval date [1] 306709 0
21/08/2020
Ethics approval number [1] 306709 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 3) is evaluating the effect of Selinexor on the incidence of COVID-19 infection in cancer patients with moderate COVID-19 infection.

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, and are hospitalised with a moderate COVID-19 infection

Study details
Participants in this study arm are randomly allocated (by chance) to one of two groups. One group will receive oral Selinexor 3 times a week for 2 weeks while the other group will receive oral placebo 3 times a week for 2 weeks

Participants will be followed for 60 days to assess effectiveness and safety.

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 104750 0
Prof Monica Slavin
Address 104750 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne
Vic
3000
Country 104750 0
Australia
Phone 104750 0
+61 3 8559 7997
Fax 104750 0
Email 104750 0
monica.slavin@petermac.org
Contact person for public queries
Name 104751 0
Mr Ronan Burder
Address 104751 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne
Vic
3000
Country 104751 0
Australia
Phone 104751 0
+61 3 8559 5000
Fax 104751 0
Email 104751 0
ronan.burder@petermac.org
Contact person for scientific queries
Name 104752 0
Dr Michelle Yong
Address 104752 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne
Vic
3000
Country 104752 0
Australia
Phone 104752 0
+61 3 8559 5000
Fax 104752 0
Email 104752 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