Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001504707
Ethics application status
Approved
Date submitted
14/10/2022
Date registered
2/12/2022
Date last updated
29/10/2024
Date data sharing statement initially provided
2/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Solving Unknown Primary cancER Earlier Diagnosis (SUPER-ED): A stepped wedge cluster randomised controlled trial implementing a Model of Care to support earlier diagnosis
Scientific title
Solving Unknown Primary cancER Earlier Diagnosis (SUPER-ED): A stepped wedge cluster randomised controlled trial implementing a Model of Care to support earlier diagnosis
Secondary ID [1] 308069 0
None
Universal Trial Number (UTN)
Trial acronym
SUPER-ED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer of Unknown Primary 327763 0
Condition category
Condition code
Cancer 324833 324833 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Fifteen participating sites from our existing network of Cancer of Unknown Primary (CUP) collaborating sites will be randomised into one of the three clusters, with 5 sites per group. Each site will commence receiving the intervention at the time corresponding to their randomised cluster. Each period corresponds to 6 months, with a one-month changeover period between Control and Intervention.

Components of the intervention include:
- Patient access to a dedicated CUP care coordinator who will provide support and care relating to the patient’s CUP diagnosis. Interaction with the CUP care coordinator will be consistent with care coordination in usual care. There may be occasional interaction remotely if necessary though it is expected that the majority of interactions are face to face.
- Patient access to the SUPER-ED CUP website which will include educational material and resources relating to their CUP diagnosis. Participants will not be asked to spend a minimum amount of time interacting with the SUPER-ED CUP website. Use of the website will be at their discretion.
- Participants will undergo a standardised diagnostic workup including a minimum diagnostic work up (e.g. physical examinations, blood tests, medical imaging scans, biopsy)
- If applicable to the patient’s case, additional investigations may be performed including site- or subtype-directed investigations based on the specific presentation (e.g. molecular testing)
- Fortnightly virtual multidisciplinary meetings (MDM) will be hosted and coordinated by the Peter MacCallum Cancer Centre’s specialist CUP service to provide expert opinion on the diagnosis or management of challenging, complex or interesting cases. Patient participants will not attend the virtual MDMs, consistent with MDMs in usual practice. It is anticipated the MDMs will run on a fortnightly basis for one hour.

Being a stepped wedge trial, all components of the intervention will be made available to participants upon enrolment. Each component will be the usual care delivered at that site, and will be delivered by the oncology team including the nurse coordinator. There are no anticipated time periods for each step of the intervention, rather, the intervention becomes the current model of care. Strategies to monitor adherence to the intervention will not be utilised.

The CUP care coordinator role is patient-facing and will encompass:
a) Assessing patients’ clinical and supportive care needs
b) Providing information and education about their cancer
c) Planning and coordinating clinical care (e.g. ordering tests, specialist appointments, clinic visits)
d) Referring to other services (social work, pastoral care etc)
e) Providing counselling
f) Delivering clinical care
g) Working within the local oncology clinics and MDM settings
h) Supporting access to the SUPER-ED website
i) Facilitating discussion of cases at the virtual CUP MDM.
No additional training will be required for the local CUP care coordinators.

The CUP website has been designed specifically for the SUPER-ED study, however the content is based on the Optimal Care Pathway (OCP) for people with cancer of unknown primary. This OCP is endorsed by a panel of experts and jurisdictional and consumer representatives that was established by the Council of Australian Governments. A wide range of clinicians, peak health organisations, consumers and carers were consulted or participated in their development. https://www.cancer.org.au/assets/pdf/cancer-of-unknown-primary-january-2020

The CUP website will include:
(a) CUP Optimal Care Pathway: Links to the CUP OCP, including explanations of medical/scientific terms and understanding the diagnostic process.
(b) Current clinical trials: A complete and regularly updated list of all Australian currently recruiting clinical trials for CUP will be maintained. These will include (but not be limited to) the SUPER suite of trials and other treatment trials that deliver therapeutics on the basis of actionable molecular targets.
(c) Clinician’s corner: Videos of Australia’s leading CUP clinicians, pathologist and molecular biologists will provide comprehensible information on state-of-the-art diagnostic, treatment and management information for CUP to upskill clinicians (and consumers) in diagnosis and disease management. Recordings of the virtual MDMs tackling challenging cases will be included here for viewing by the patient, carers and their treatment team in a password protected area.
(d) Understanding CUP: Individual videos of patients and carers talking about their real-world experience of living with CUP covering: understanding of the diagnostic process, experimental diagnostic molecular tests, treatment and care experiences, uncertainty and other emotions.
(e) Consultation help for patients: Printable versions of recommended diagnostic tests drawn from the CUP OCP and question prompt lists for patients to take to their next clinician consultation to guide discussion.
(f) More information: Links to trustworthy external resources, including other patient information and support via the Cancer Council (such as the Cancer Information and Support Service 131120); CUP Foundation UK, and other reputable evidence-based websites.
Intervention code [1] 324520 0
Diagnosis / Prognosis
Comparator / control treatment
As per usual care, sites during the control phase will be provided with links to the Australian CUP OCP guidelines (clinician and patient versions); the Cancer Council booklet ‘Understanding Cancer of Unknown Primary (hardcopy or links to website) and access to a Cancer Council Helpline (131120).
Control group
Active

Outcomes
Primary outcome [1] 332650 0
Time to completion of minimum diagnostic workup - Number of days from the date of imaging that first detected metastasis, to the date of completion of minimum diagnostic workup. This data will be sourced through a patient medical records audit.
Timepoint [1] 332650 0
This outcome data will be collected at four months after the patient's first imaging investigation that detected metastasis and will be assessed at the conclusion of the study.
Secondary outcome [1] 414234 0
Primary tumour type diagnosed - excluding patients who have a benign diagnosis, The proportion of patients who have a primary tumour type diagnosed after completion of the standardised diagnostic tests out of the total proportion of patients recruited who completed standardised diagnostic workup. This data will be sourced through a patient medical records audit.
Timepoint [1] 414234 0
This outcome data will be collected at four months after the patient's first imaging investigation that detected metastasis and will be assessed at the conclusion of the study.
Secondary outcome [2] 414235 0
Clinical trial participation rates - Proportion of patients with a CUP diagnosis recruited to any clinical trial out of the total proportion of patients recruited and who completed standardised diagnostic workup. This data will be sourced through a patient medical records audit.
Timepoint [2] 414235 0
This outcome data will be collected at four months after the patient's first imaging investigation that detected metastasis and will be assessed at the conclusion of the study.
Secondary outcome [3] 414236 0
Patient-reported physical, social and mental health.
Patient-Reported Outcomes Measurement Information System (PROMIS) short forms measuring:
Emotional Distress – Anxiety
Timepoint [3] 414236 0
4 months after the patient's first imaging investigation that detected metastasis
Secondary outcome [4] 414237 0
Mishel Uncertainty in Illness Scale – Community Form (MUIS-C) measuring:
Patient-reported uncertainty
Timepoint [4] 414237 0
4 months after the patient's first imaging investigation that detected metastasis
Secondary outcome [5] 414238 0
Patient-reported understanding

Single items, drawn from the UK Cancer Patient Experience Survey and adapted for Australia assessing: understanding of their diagnosis, diagnostic tests and treatment, adequacy of communication, information and experiences with hospital staff and the health system.

Timepoint [5] 414238 0
4 months after the patient's first imaging investigation that detected metastasis
Secondary outcome [6] 415842 0
Patient-reported physical, social and mental health.
Patient-Reported Outcomes Measurement Information System (PROMIS) short forms measuring:
Emotional Distress – Depression
Timepoint [6] 415842 0
4 months after the patient's first imaging investigation that detected metastasis
Secondary outcome [7] 415843 0
Patient-reported physical, social and mental health.
Patient-Reported Outcomes Measurement Information System (PROMIS) short forms measuring:
Fatigue
Timepoint [7] 415843 0
4 months after the patient's first imaging investigation that detected metastasis
Secondary outcome [8] 415844 0
Patient-reported physical, social and mental health.
Patient-Reported Outcomes Measurement Information System (PROMIS) short forms measuring:
Pain interference
Timepoint [8] 415844 0
4 months after the patient's first imaging investigation that detected metastasis
Secondary outcome [9] 415845 0
Patient-reported physical, social and mental health.
Patient-Reported Outcomes Measurement Information System (PROMIS) short forms measuring:
Pain intensity
Timepoint [9] 415845 0
4 months after the patient's first imaging investigation that detected metastasis
Secondary outcome [10] 415846 0
Patient-reported physical, social and mental health.
Patient-Reported Outcomes Measurement Information System (PROMIS) short forms measuring:
Sleep disturbance
Timepoint [10] 415846 0
4 months after the patient's first imaging investigation that detected metastasis
Secondary outcome [11] 415847 0
Patient-reported physical, social and mental health.
Patient-Reported Outcomes Measurement Information System (PROMIS) short forms measuring:
Physical function
Timepoint [11] 415847 0
4 months after the patient's first imaging investigation that detected metastasis
Secondary outcome [12] 415848 0
Patient-reported physical, social and mental health.
Patient-Reported Outcomes Measurement Information System (PROMIS) short forms measuring:
Satisfaction with social roles
Timepoint [12] 415848 0
4 months after the patient's first imaging investigation that detected metastasis

Eligibility
Key inclusion criteria
- 18 years of age or older
- Presenting with malignancy of undefined primary origin, i.e. suspicion of metastatic malignancy without an obvious primary site on imaging
- Clinically appropriate to undergo diagnostic work-up, as determined by the treating clinician
-Able to provide written or verbal consent. For participants with limited English proficiency a legally acceptable representative may be a witness such as a qualified interpreter.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Unable to provide (written or verbal) consent.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The sequence will be block randomisation to ensure each cluster contains 5 hospitals.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
The 15 participating sites have been selected from our existing network of health services that are collaborators of CUP research.
Grouping of the sites into clusters and randomisation of the clusters will be performed remotely by the Study Statistician. The participating sites will be randomised to different conditions as part of the stepped wedge cluster design. The patients themselves will not be randomised, instead they will be asked to provide clinical data and PROMs data relating to the model of care that their service is currently providing.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size calculation is based on a Type 1 error rate of 5% and a Type 2 error rate of 20%. Our data on 207 cases found that the mean(sd) time from identification of metastatic disease to diagnosis was 57.4(49.1). The aim of this study is to reduce the time to diagnosis from 57.4 to 30 days. A total sample size of 240 (20 subjects per cluster per period or 4 subjects per site per period) gives 80% power to detect this difference.

Analyses will be conducted on an intention-to-treat basis and the trial conducted and reported according to CONSORT extension for stepped wedge guidelines. Missing data will be imputed using multiple imputations, redrawing 50 samples.

For the primary endpoint analysis of days from detection of metastasis to minimum workup, a random effects linear mixed model will be used, with days as the dependent variable and adjusting for group assignment and period. Site and cluster will be entered as a random effects and covariance matrices will be used to model the correlation of random effects and within-group effects over time to improve model fit. Specifically, we will explore model fit using Stata’s residuals and covariance options.
Sensitivity analyses will be conducted linear regression, with days as the dependent variable, time as the independent variable, clustering over site to account for correlated errors.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/10/2024
Actual
Date of last participant enrolment
Anticipated
30/06/2027
Actual
Date of last data collection
Anticipated
31/10/2027
Actual
Sample size
Target
240
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,TAS,VIC
Recruitment hospital [1] 23243 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 23245 0
Border Medical Oncology - Albury
Recruitment hospital [3] 23246 0
Westmead Private Hospital - Westmead
Recruitment hospital [4] 23247 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [5] 23248 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [6] 23250 0
Royal Hobart Hospital - Hobart
Recruitment hospital [7] 23251 0
Launceston General Hospital - Launceston
Recruitment hospital [8] 23252 0
Southwest Health Care - Warrnambool - Warrnambool
Recruitment hospital [9] 23253 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [10] 23254 0
The Alfred - Melbourne
Recruitment hospital [11] 23255 0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
Recruitment hospital [12] 23256 0
Eastern Health - Box Hill
Recruitment hospital [13] 23258 0
Peninsula Oncology Centre - Frankston
Recruitment hospital [14] 26469 0
Blacktown Hospital - Blacktown
Recruitment hospital [15] 27285 0
Dandenong Hospital- Monash Health - Dandenong
Recruitment postcode(s) [1] 38613 0
3000 - Melbourne
Recruitment postcode(s) [2] 38615 0
2640 - Albury
Recruitment postcode(s) [3] 38616 0
2145 - Westmead
Recruitment postcode(s) [4] 38617 0
0810 - Tiwi
Recruitment postcode(s) [5] 38618 0
4029 - Herston
Recruitment postcode(s) [6] 38620 0
7000 - Hobart
Recruitment postcode(s) [7] 38621 0
7250 - Launceston
Recruitment postcode(s) [8] 38622 0
3280 - Warrnambool
Recruitment postcode(s) [9] 38623 0
3220 - Geelong
Recruitment postcode(s) [10] 38624 0
3550 - Bendigo
Recruitment postcode(s) [11] 38625 0
3128 - Box Hill
Recruitment postcode(s) [12] 38627 0
3199 - Frankston
Recruitment postcode(s) [13] 42449 0
2148 - Blacktown
Recruitment postcode(s) [14] 43372 0
3175 - Dandenong

Funding & Sponsors
Funding source category [1] 312325 0
Government body
Name [1] 312325 0
Department of Health and Aged Care, Medical Research Future Fund (MRFF)
Country [1] 312325 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
Swinburne Research
Level 1, Swinburne Place South,
24 Wakefield Street Hawthorn,
VIC, 3122
Country
Australia
Secondary sponsor category [1] 313878 0
None
Name [1] 313878 0
Address [1] 313878 0
Country [1] 313878 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311692 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 311692 0
Ethics committee country [1] 311692 0
Australia
Date submitted for ethics approval [1] 311692 0
08/08/2022
Approval date [1] 311692 0
04/10/2022
Ethics approval number [1] 311692 0

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

Contacts
Principal investigator
Name 122018 0
Prof Linda Mileshkin
Address 122018 0
Peter MacCallum Cancer
305 Grattan Street
Melbourne, Victoria
3000 Australia
Country 122018 0
Australia
Phone 122018 0
+61 03 8559 7902
Fax 122018 0
Email 122018 0
[email protected]
Contact person for public queries
Name 122019 0
Natalie Richards
Address 122019 0
Peter MacCallum Cancer Centre
305 Grattan St, Melbourne VIC 3000
Country 122019 0
Australia
Phone 122019 0
+61 3 8559 7453
Fax 122019 0
Email 122019 0
[email protected]
Contact person for scientific queries
Name 122020 0
Linda Mileshkin
Address 122020 0
Peter MacCallum Cancer
305 Grattan Street
Melbourne, Victoria
3000 Australia
Country 122020 0
Australia
Phone 122020 0
+61 03 8559 5000
Fax 122020 0
Email 122020 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.