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Trial registered on ANZCTR


Registration number
ACTRN12623001221640
Ethics application status
Approved
Date submitted
13/10/2023
Date registered
28/11/2023
Date last updated
28/11/2023
Date data sharing statement initially provided
28/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
CUPID: Transforming Cancer of Unknown Primary with Intelligent Diagnostics
Scientific title
Transforming Cancer of Unknown Primary with Intelligent Diagnostics: Identifying the Primary Cancer using Tissue of Origin Analysis, and Detecting Molecular Targets for Personalised Therapy
Secondary ID [1] 310738 0
MRF2007652
Universal Trial Number (UTN)
Trial acronym
CUPID
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer
 331686 0
Condition category
Condition code
Cancer 328423 328423 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
- Tissue of Origin (ToO) will be conducted on previously collected samples, A fresh biopsy will be requested only if the previous biopsy sample is inadequate to enable sufficient analysis in line with the study plan. Please note, that the above process now represents 'optimal' management of patients with advanced cancer, especially for a cancer of unknown primary, where cancer biology and site of origin remain unclear and unknown. There are no 'standard' treatment options, and the prognosis is poor. The optimal management plan (outside of research) is now supporting an approach that includes genomic profiling of the cancers as this may better guide management, improve treatment selection and improve patient outcomes. In Australia, the framework for doing such testing and analysis, with reporting of results and enacting management based on these results, remains in development. There is no 'standard process' and the reach of molecular oncology is not universal or applied in an equitable way. Our study is deigned in a manner that outlines a framework, including the development of a state-wide molecular oncology multi-disciplinary meeting, and this pathway and framework will be explored as part of the study. We are particularly keen to address the experience of Indigenous Australians within the current landscape and within the planned study framework.

- Somatic tissue profiling will occur in parallel to ToO (in fact, it will be a step-wise sequence approach - with samples moving from the genomic mutation laboratory in Adelaide to the ToO testing lab in Melbourne). All the blood (1 x 9ml lithium heparin peripheral blood sample ) and biopsy samples (Sample (FFPE block) with MINIMUM 20% tumour content with minimal necrosis and 200ng DNA (send at RT)) will be collected (tissue from previous diagnostic samples) as soon as the patient is enrolled and agrees to proceed towards a detailed diagnosis. A fresh biopsy will be requested only if the previous biopsy sample is inadequate to enable sufficient analysis in line with the study plan. This is also inline with 'standard practice', as genomic profiling as such cancers is now considered 'best practice', where genomic testing is available.

- The genomic pathology testing and reporting will be conducted by specialist genomic pathologists. The specialist pathologists involved in the research are experienced at detecting the known actionable mutations. Another group of specialist pathologists will perform the tissue of origin testing, and will provide a report based on the test results. These pathologists have worked on ToO testing, and have published their results. They will continue this research as part of our study, hoping to validate previous findings. Together, all specialist pathologists and the involved medical oncologists and other treating specialists will meet through the 'Molecular MDT' to discuss the results and consider the implications of the findings with respect to patient management. This process will be studied as part of the planned research.

- The anticipated time needed to obtain the results of the genomic testing is between 4-8 weeks post tissue collection. Patients will not be expected to wait for these results. Patients are expected to commence 'standard therapy' in the absence of knowing the results from the planned genomic tests. The results, however, may guide subsequent therapy. In selected cases, and if this meets with the patient's preference, treatment may be commenced after the genomic results are available. The above sequence and process outlines what is rapidly becoming an 'optimal' and 'standard' clinical care pathway, not a 'research pathway'. Our research intends to examine this pathway,

-The aspects of Optimal care pathway will be assessed by the following steps:
1. Prevention and early detection
2. Presentation, initial investigations and referral
3. Diagnosis, staging and treatment planning
4. Treatment
5. Care after initial treatment and recovery
6. Managing recurrent or progressive disease
7. End-of-life care".

- Compliance assessments will be conducted by assigned research staff. These staff members will have access to clinical records.

-The assessment will be carried out via a checklist extracted from OCP and compared with Sunrise EMR/medical records whether the pathway/steps were followed as per OCP or not.

-The OCP will be implemented in parallel to the ToO and Somatic mutation profiling.
as per OCP at step 2 when CUP specific sub-set and CUP non-specific sub-set patients will be referred to oncologist, progressing on to step 3; further diagnostic workup following ToO and Somatic mutation profiling will come in place to match targeted therapies to actionable mutations. In other words, the OCP will be assessed along the entire patient care continuum.
Intervention code [1] 327145 0
Diagnosis / Prognosis
Comparator / control treatment

The the medical record numbers will be identified from historical data (1 January 2000 to 31 December 2022) sourced/requested form South Australian/National Cancer registry, which will be further identified in Sunrise EMR and compared accordingly for relevant data capture.
Control group
Historical

Outcomes
Primary outcome [1] 336261 0
To identify the proportion of patients initially diagnosed with CUP, or suspected to have CUP, who then get assigned a primary cancer using tissue of origin analysis
Timepoint [1] 336261 0

Tissue of origin and Somatic mutation profiling results = within 4-8 weeks of sampling
Secondary outcome [1] 428187 0
To identify the proportion of patients initially diagnosed with CUP, or suspected to have CUP, who then get assigned a primary cancer by somatic molecular profiling
Timepoint [1] 428187 0
Upon completion of study
Secondary outcome [2] 428189 0
To identify the proportion of patients initially diagnosed with CUP who get a diagnosis other than CUP
Timepoint [2] 428189 0
4-6 weeks after study enrolment
Secondary outcome [3] 428190 0
To identify the proportion of patients who have an actionable mutation with a recognised matched therapy (or therapies)
Timepoint [3] 428190 0
Upon completion of study.
Secondary outcome [4] 428191 0
To determine the awareness of the nationally recognised Optimal Care Pathway (OCP) for all patients with CUP.
Timepoint [4] 428191 0
the outcome will assess medical professionals awareness regarding OCP, which will be assessed via a HREA approved study-specific survey conducted at the start and end of the study.
Secondary outcome [5] 428192 0
To identify the proportion of patients whose treatment was changed after a diagnosis other than CUP was made
Timepoint [5] 428192 0
Upon study completion.
Secondary outcome [6] 428193 0
To identify the proportion of patients who were able to receive optimal therapy based on their somatic mutation profiling results
Timepoint [6] 428193 0
Upon study completion.
Secondary outcome [7] 428194 0
Overall survival of patients with a CUP diagnosis following the implementation of the OCP and to compare it with a historical comparator cohort
Timepoint [7] 428194 0
Upon study completion

Eligibility
Key inclusion criteria
Eligible participants must fulfill all the following criteria:
1. Age 18 years or more
2. Suspected or confirmed CUP diagnosis
3. Willing to provide informed consent
4. Able to understand English or understand study involvement through interpreter services
5. No prior systemic therapy for the treatment of CUP
• Patients who have received prior surgery and/or radiotherapy (including radioembolization of tumour) are eligible upon evidence of cancer recurrence or progression.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who meet any of the following criteria will be excluded from study entry:
1. Metastatic disease from a known primary site
2. Patients with histology and immunohistology profiles (per 2015 ESMO guidelines) that are compatible with extragonadal germ-cell tumours, neuroendocrine tumours, sarcoma, melanoma, mesothelioma, haematological malignancies (this list is not limitative)

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
29/11/2023
Actual
Date of last participant enrolment
Anticipated
23/10/2025
Actual
Date of last data collection
Anticipated
26/04/2026
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NT,SA
Recruitment hospital [1] 25704 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 25705 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [3] 25706 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [4] 25707 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [5] 25708 0
Mount Gambier and Districts Health Service - Mount Gambier
Recruitment hospital [6] 25709 0
Royal Darwin Hospital - Tiwi
Recruitment postcode(s) [1] 41533 0
0810 - Tiwi
Recruitment postcode(s) [2] 41528 0
5000 - Adelaide
Recruitment postcode(s) [3] 41530 0
5011 - Woodville
Recruitment postcode(s) [4] 41529 0
5042 - Bedford Park
Recruitment postcode(s) [5] 41531 0
5112 - Elizabeth Vale
Recruitment postcode(s) [6] 41532 0
5290 - Mount Gambier

Funding & Sponsors
Funding source category [1] 314969 0
Government body
Name [1] 314969 0
Medical Research Future Fund, Dept of Health and Aged care, Australian Government
Country [1] 314969 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Sturt Road, Bedford Park, SA 5042
Country
Australia
Secondary sponsor category [1] 316969 0
None
Name [1] 316969 0
Address [1] 316969 0
Country [1] 316969 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313943 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 313943 0
Flinders Centre for Innovation in Cancer, Flinders Drive, Bedford Park, SA 5042
Ethics committee country [1] 313943 0
Australia
Date submitted for ethics approval [1] 313943 0
30/05/2023
Approval date [1] 313943 0
13/06/2023
Ethics approval number [1] 313943 0

Summary
Brief summary
This research is conducted to initially diagnose Cancer of Unknown Primary (CUP) at the DNA level using Somatic molecular profiling and tissue of origin assay and to measure the implementation of Optimal Care Pathway (OCP) .

Who is it for?
You may be eligible to join this study if you are aged 18 years and older, have suspected or confirmed CUP diagnosis and no prior treatment for CUP

Study details
All participants in this study will have treatment according to the optimal care pathway along with the use of tissue of origin classifier and comprehensive somatic mutation profiling.

Participants will be asked to sign a consent form. Access to your health records may be required to help interpret the results; therefore, your participation will involve giving us permission to collect information about your cancer diagnosis and use of health services. This research will be monitored by Flinders Medical Centre Medical Oncology Department Clinical Trials unit.
Participation in this study involves somatic molecular profiling and tissue of origin test which will be described in detail below.
Somatic molecular profiling and tissue of origin assay
Cancer cells have changes in their DNA (the "instruction book" for the cells in your body) that cause uncontrolled growth. When you were diagnosed with cancer, you had a piece of tissue removed from your tumour(s) (called a “biopsy”) to confirm what type of cancer it is. Testing on the tumour (somatic molecular profiling) may help identify where your cancer started. Furthermore, the test may identify genetic changes in your cancer that may respond to anti-cancer medicines. Your doctor may then tailor your treatment accordingly. Treatment in this research project will be determined and given by your treating doctors. The trial does NOT provide treatment.


Participants will be followed-up every month to assess the outcomes of the matched/recognised therapies in participants.

It is hoped that this research project might or might not improve your health but the information that is learned may help other people who have a similar medical condition in the future.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129870 0
Prof Chris Karapetis
Address 129870 0
Flinders Centre for Innovation in Cancer, Flinders Drive, Bedford Park, SA 5042
Country 129870 0
Australia
Phone 129870 0
+61 8 8204 8997
Fax 129870 0
Email 129870 0
chris.karapetis@sa.gov.au
Contact person for public queries
Name 129871 0
Mr CUPID Coordinator
Address 129871 0
Flinders Centre for Innovation in Cancer, Flinders Drive, Bedford Park, SA 5042
Country 129871 0
Australia
Phone 129871 0
+61 8 8204 6200
Fax 129871 0
Email 129871 0
health.cupid@sa.gov.au
Contact person for scientific queries
Name 129872 0
Mr CUPID Coordinator
Address 129872 0
Flinders Centre for Innovation in Cancer, Flinders Drive, Bedford Park, SA 5042
Country 129872 0
Australia
Phone 129872 0
+61 8 8204 6200
Fax 129872 0
Email 129872 0
health.cupid@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
May make the data available, if requested by investigators for project identified as worthy. Data will be de-identified. No plans at this stage for this.


What supporting documents are/will be available?




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.