Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000935831
Ethics application status
Approved
Date submitted
31/05/2021
Date registered
16/07/2021
Date last updated
14/10/2024
Date data sharing statement initially provided
16/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Applicability of Positron Emission Tomography using Gallium-68 labelled Fibroblast Activating Protein Inhibitor for the diagnosis, staging and treatment of pancreatic cancer.
Scientific title
A pilot study to evaluate the diagnostic and therapeutic applications of FAPI-PET in pancreatic cancer.
Secondary ID [1] 303911 0
Nil known.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic Cancer 321494 0
Condition category
Condition code
Cancer 319248 319248 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will attend the RBWH Nuclear Imaging Department, or the Herston Imaging Research Facility (HIRF) on the RBWH campus, to undergo FAPI-PET scan with superimposed low dose computed tomography (FAPI-PET/CT).

The procedure requires insertion of an intravenous (IV) line for injection of the tracer. The specific tracer to be used is Gallium-68-FAPI-46 at a dose of 250MBq. Participants will have three separate PET/CT scans on the same day following just one injection of the tracer:
1. 10 minutes following injection of tracer: Scan over pancreas only (about 15 minutes lying on the scanner bed).
2. 60 minutes following injection of tracer: Scan of head to upper thighs. (about 30 minutes lying on the scanner bed).
3. 180 minutes following injection of tracer: Scan over pancreas only. (about 15 minutes lying on the scanner bed).

The above imaging protocol represents the maximum radiation exposure a participant can receive as part of this study. Provided the data obtained is contributory to study outcomes, certain participants may undergo fewer scanning sessions or have less body area scanned.

The time commitment for taking part in this study is 4 hours at maximum. Each participant will attend HIRF for the FAPI-PET/CT imaging protocol only once. The scan will take place within 14 days of enrolment in the study, although preferably within 7 days. FAPI-PET/CT is to take place prior to delivery of any surgical or systemic therapy, and prior to direct biopsy of the primary tumour mass for patients without known metastatic disease.

The scan will be administered by staff with relevant qualifications in PET imaging at the RBWH Nuclear Imaging department or HIRF. FAPI-PET/CT images will be interpreted by a qualified nuclear medicine physician.

The results of FAPI-PET/CT will be relayed to the treating clinician only if there could be a change to management as a result. Such cases will be re-discussed at the relevant multi-disciplinary team (MDT) meeting, and change to the treatment plan as a result will only occur if metastatic lesions are confirmed on biopsy or other established imaging techniques. See "study design" for further details.

Participants will be followed up as usual by their treating clinician according to usual protocols. The researchers will collect information obtained at clinical follow up, as well as results of FAPI-PET/CT to evaluate study outcomes.

If their pancreatic lesion undergoes surgical resection or biopsy, consenting participants will have excess tissue samples sent to the Translational Research Institute to undergo additional analysis. More specifically, this will involve immunohistochemistry to quantify expression of Fibroblast Activating Protein (FAP), which is the cellular target of FAPI-PET/CT.
Intervention code [1] 320216 0
Diagnosis / Prognosis
Comparator / control treatment
Nil.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327121 0
Proportion of participants where all measurable sites of pancreatic cancer (greater than 10mm) have a maximum standardised uptake value (SUVmax) exceeding 10 as measured by FAPI-PET/CT at any time point after injection of tracer. This will be evaluated by the qualified nuclear medicine physician interpreting the scan.
Timepoint [1] 327121 0
At the time of FAPI-PET/CT scan.
Primary outcome [2] 327122 0
The proportion of patients with potentially resectable pancreatic cancer on conventional staging who have new distant metastases detected on FAPI-PET/CT. New distant metastases will be screened for by the qualified nuclear medicine physician interpreting the PET scan. Confirmation of metastatic deposits will be with histopathology or other established radiological modalities.
Timepoint [2] 327122 0
At the time of pre-operative disease staging.
Primary outcome [3] 327123 0
SUVmax as measured by FAPI-PET/CT, intra-lesional biodistribution as measured by FAPI-PET/CT, and temporal biodistribution as measured by serial FAPI-PET/CT; in malignant compared to benign pancreatic lesions. PET imaging parameters will be evaluated by the qualified nuclear medicine physician interpreting the scan. All pancreatic lesions will undergo tissue classification with surgical or biopsy specimens to determine if they are benign or malignant.
Timepoint [3] 327123 0
At the time of pathological assessment of the pancreatic lesion.
Secondary outcome [1] 393867 0
Disease free survival as determined by review of medical records from clinical follow up.
Timepoint [1] 393867 0
Assessed for 24 months after enrolment in the study.
Secondary outcome [2] 398336 0
Overall survival as determined by hospital medical records.
Timepoint [2] 398336 0
Assessed for 24 months after enrolment in the study.
Secondary outcome [3] 422543 0
Expression of Fibroblast Activating Protein (FAP) in resection/biopsy specimens belonging to participants. This will be measured as a 'proportion' and 'intensity' scored for both neoplastic and stromal cells following immunohistochemical staining for FAP. This will be correlated with SUVmax of the same lesion on FAPI-PET/CT, as well as grade of dysplasia or malignancy.
Timepoint [3] 422543 0
At time of immunohistochemical analysis of participant tissue specimens.

Eligibility
Key inclusion criteria
This will be a dual centre, prospective, single arm study. We aim to recruit up to 62 patients in this study.
Key Inclusion criteria.
Patients referred to any hepato-pancreato-biliary (HPB) surgeon or oncologist with admitting rights at the Royal Brisbane and Women’s Hospital (RBWH) and Princess Alexandra Hospital (PAH) will be considered for inclusion. Patients will be recruited into 1 of 3 groups based on the following inclusion criteria:

a. Patients with pancreatic cancer and metastases. Must satisfy the following:
i. Histology / cytology specimen from primary or metastatic lesion highly suggestive of pancreatic or peri-ampullary adenocarcinoma.
ii. Distant metastases diagnosed on conventional cross-sectional imaging.

b. Patients with probable pancreatic cancer that is potentially resectable. Must satisfy the following:
i. Solid or infiltrating mass arising from pancreatic parenchyma on cross sectional imaging or common bile duct brushings highly suggestive of pancreatic or peri-ampullary adenocarcinoma.
ii. Has undergone cross sectional imaging of chest abdomen and pelvis without the diagnosis of metastases or local un-resectable features.
iii. Has not undergone direct biopsy of the tumour mass prior to FAPI-PET/CT.

c. c. Patients with a cystic pancreatic lesion without confirmed malignancy. Must satisfy the following:
i. Cystic pancreatic lesion detected on cross sectional imaging or endoscopic ultrasound.
ii. Patient exhibits at least one “worrisome feature” or “high-risk stigmata” according to Fukuoka guidelines: [Tanaka et al 2017: see below reference].

Additional Inclusion criteria.
i. No known problems of peripheral intravenous access.
ii. Able to provide informed, signed consent.
iii. All women of childbearing age considered for the study must have a pregnancy test prior to enrolment.

Reference:
Tanaka, M., et al., Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology, 2017. 17(5): p. 738-753.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria
i. Aged under 18 years of age.
ii. Administered a radioisotope within 5 half-lives prior to the intended scan.
iii. Patients with allergies to the FAPI or FDG PET tracer.
iv. Pregnant patients.
v. Patients who have started chemotherapy or radiotherapy for their disease prior to FAPI-PET/CT.
vi. Patients who have undergone surgery for their disease prior to FAPI-PET/CT.
vii. Unable to lie flat to tolerate PET scanning.
viii. Prior history of other malignancy within the last 2 years.

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)
N/A.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
All patients recruited will undergo FAPI-PET/CT as described in "intervention/exposure". This is in addition to conventional staging with contrast enhanced CT, magnetic resonance, ultrasound, endoscopy, laparoscopy or FDG-PET/CT if it is considered part of their usual work up. Endoscopic retrograde cholangio-pancreatography (ERCP) with stent and/or brushings prior to FAPI-PET/CT is permitted in all cases. Patients are only to have undergone direct biopsy of the tumour mass prior to FAPI-PET/CT if they fall into eligibility group a (distant metastases already diagnosed).

For group a, patients with known metastatic disease, the treating clinician will be blinded to the results of FAPI-PET/CT. Findings from FAPI-PET/CT will not influence management of patients in this cohort.

For group b and c, patients with possible/probable pancreatic cancer that is potentially resectable, the nuclear physician interpreting FAPI-PET/CT will notify the treating surgeon only if potential new distant metastases have been detected. Such cases will be re-discussed at the relevant multi-disciplinary team (MDT) meeting, and change to the treatment plan as a result will only occur if metastatic lesions are confirmed on biopsy or other established imaging techniques.

FAPI-PET/CT is not to be used in lieu of any other staging modality, including FDG-PET/CT.

Representative slides from excess Study Participant tissue samples will be prepared by the pathology department at the treating hospital. These will be collected in accordance with the study protocol. Slides will undergo analysis by investigators at the Translational Research Institute. No Study Participant personal information will be provided to the Mater. Tissue slides will be stored at room temperature in the laboratory in which they will undergo analysis. Once tissue slides have been stained, scored and all relevant data collected they will be stored by Mater for up to 15 years to enable IHC analysis for other PET targets that might become relevant in future HREC approved research.

For participants who have been enrolled and undergone FAPI-PET/CT scan prior to version 4 of the Patient Information and Consent Form (PICF), analysis of their tissue samples by investigators at the Mater will be conditional on that participant agreeing to and signing version 4 of the PICF.

This study is intended as a pilot study for proof of principle. During this pilot study the imaging and pathology study protocols will be reviewed for logistics and feasibility to inform future clinical trial design.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Primary outcome 1 (Proof of concept).
We will determine the proportion - and 95% confidence interval- of participants for which all known pancreatic cancer sites (>10mm) had a maximum standardised uptake value (SUVmax) of >10 measured by FAPI-PET/CT at 10,60 or 180 minutes after tracer injection.

Primary Outcome 2 (Proof of concept).
We will determine the proportion - and 95% confidence interval - of participants with potentially resectable disease on conventional staging who had new distant metastases detected on FAPI-PET/CT.

Primary outcome 3. (Proof of concept)
We will compare SUVmax of the primary lesion as measured by FAPI-PET/CT at 10, 60 and 180 minutes after tracer injection between benign and malignant pancreatic lesions. We will use parametric or non parametric comparison depending on the distribution of SUVmax. At each time point we will characterise intra-lesional bio-distribution in benign and malignant pancreatic lesions. We will characterise the pattern of change in SUVmax over time as determined by serial FAPI-PET/CT for benign and malignant pancreatic lesions.

Secondary Outcome 1.
For patients who undergo resection of pancreatic cancer we will determine recurrence within 6 months of surgery. We will compare SUVmax of the primary tumour as measured by FAPI-PET/CT at 60 minutes after tracer injection between groups. We will use parametric or non parametric comparison depending on distribution of SUVmax. We will utilise Kaplan-Meier time to event curves to test for a difference in overall and disease free survival for patients whose primary pancreatic cancer has SUVmax >10 as measured by FAPI-PET/CT 60 minutes after tracer injection.

Secondary Outcome 2.
In patients with sufficient tissue to perform immunohistochemistry we will perform linear regression adjusting for potential confounders to determine if proportion and intensity of staining is related to SUVmax of primary pancreatic lesions. We will perform similar tests for correlation with expression of other biomarkers. We will do this separately for both stromal and neoplastic expression. For each pattern of FAP expression (i.e., stromal cells only, neoplastic cells only, or mixed) we will determine median SUVmax-p and IQR. We will compare groups using parametric or non-parametric tests depending on distribution of absolute SUVmax-p.

We will also compare FAP expression (proportion, intensity, and dominant staining pattern) between benign and malignant lesions.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/08/2021
Actual
10/11/2021
Date of last participant enrolment
Anticipated
30/12/2024
Actual
Date of last data collection
Anticipated
30/12/2026
Actual
Sample size
Target
62
Accrual to date
46
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 19073 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 19074 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 33623 0
4029 - Herston
Recruitment postcode(s) [2] 33624 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 308298 0
Charities/Societies/Foundations
Name [1] 308298 0
Royal Brisbane and Women's Hospital (RBWH) Foundation
Country [1] 308298 0
Australia
Funding source category [2] 313996 0
Charities/Societies/Foundations
Name [2] 313996 0
PanKind (The Australian Pancreatic Cancer Foundation)
Country [2] 313996 0
Australia
Primary sponsor type
Hospital
Name
Royal Brisbane & Women's Hospital
Address
Butterfield Street, Herston
QLD, Australia, 4029
Country
Australia
Secondary sponsor category [1] 309104 0
Hospital
Name [1] 309104 0
Princess Alexandra Hospital
Address [1] 309104 0
199 Ipswich Rd
Woolloongabba
QLD, 4102
Country [1] 309104 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308274 0
Royal Brisbane and Women's Hospital Human Research Ethics Committee
Ethics committee address [1] 308274 0
Ethics committee country [1] 308274 0
Australia
Date submitted for ethics approval [1] 308274 0
08/04/2021
Approval date [1] 308274 0
27/05/2021
Ethics approval number [1] 308274 0
HREC/2021/QRBW/75096

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

Contacts
Principal investigator
Name 110150 0
Dr William McGahan
Address 110150 0
Royal Brisbane and Women's Hospital
Butterfield Street, Herston
QLD, 4029
Country 110150 0
Australia
Phone 110150 0
+61 418987371
Fax 110150 0
Email 110150 0
[email protected]
Contact person for public queries
Name 110151 0
William McGahan
Address 110151 0
Royal Brisbane and Women's Hospital
Butterfield Street, Herston
QLD, 4029
Country 110151 0
Australia
Phone 110151 0
+61 418987371
Fax 110151 0
Email 110151 0
[email protected]
Contact person for scientific queries
Name 110152 0
William McGahan
Address 110152 0
Royal Brisbane and Women's Hospital
Butterfield Street, Herston
QLD, 4029
Country 110152 0
Australia
Phone 110152 0
+61 418987371
Fax 110152 0
Email 110152 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
No ethical approval to share individual patient data.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11308Study protocol    381773-(Uploaded-10-04-2023-12-43-34)-Study-related document.docx
11310Informed consent form    381773-(Uploaded-10-04-2023-12-44-07)-Study-related document.docx



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.