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Trial registered on ANZCTR


Registration number
ACTRN12623001098628
Ethics application status
Approved
Date submitted
13/09/2023
Date registered
20/10/2023
Date last updated
25/10/2023
Date data sharing statement initially provided
20/10/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the role of interim Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) and blood markers to predict local and regional failure in patients with anal squamous cell carcinoma.
Scientific title
Interim Magnetic Resonance Imaging (MRI), fluorodeoxyglucose (FDG)-positron emission tomography (PET), and circulating tumour human papillomavirus (HPV) DNA during chemoRadiotherapy In p16-positive AnaL squamous cell carcinoma: The IMPERIAL Study
Secondary ID [1] 310588 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
IMPERIAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anal Cancer 331450 0
Condition category
Condition code
Cancer 328188 328188 0 0
Bowel - Anal

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
FDG-PET, Biomarker testing with optional MRI will be administered to participants eligible and consenting to this study.
Patients will receive 5-6 weeks of CRT depending on their staging.
FDG- PET scans will be performed at 3 timepoints for all patients. PETpre is to be completed prior to commencement of CRT, PETinterim during the second week of CRT and PETpost at 3 months post CRT. If the PETpost at 3 months post-treatment FDG-PET reveals a partial response, and the patient does not have clinically progressive disease, a 4th FDG-PET (PETprogress) will be performed at 5 months after completion of CRT.
The scans will be performed in the Nuclear Medicine department at Liverpool Hospital on a digital PET scanner (GE Healthcare, Discovery MI) in 3D mode for a total acquisition time of 1.5 – 2.5 min per bed position, adjusted according to the patient weight, from mid brain to proximal femora at about 1 hour post injection of a radiotracer called fluorodeoxyglucose (3.4 MBq/Kg). PET images will be reconstructed using GE VUE Point FX (Time of Flight) algorithm into a 256 x 256 matrix size with a slice thickness of 3.75 to 4.0 mm, and GE Q.Clear iterative reconstruction and if required Q-static motion-corrected respiratory gated algorithm for measurement of SUV and other volumetric parameters. Transmission scans and attenuation corrections will be obtained by using a 128-slice CT, using helical mode without the use of a contrast medium. CT images are to be acquired at 3.75 to 5mm slice thickness and reconstructed to a transaxial matrix size of 512 x 512. The current (30-40 mAs) and voltage (120-140 kV) are varied according to the patient weight. All FDG PET images will be analysed by the consensus reading of a nuclear medicine physician and a radiation oncologist.

Patients who are eligible for the main study will be screened with an MRI safety questionnaire and if no contraindications to MRI are found, will be offered enrollment on the MRI sub-study. For this study, MRI will be performed at 3 timepoints (baseline prior to radiotherapy, Mid treatment of CRT and 3 months post CRT). It is currently routine practice at the recruiting centres to acquire an MRI at the time of radiotherapy simulation. To reduce the number of visits to the hospital, MRIinterim and MRIpost should be performed on the same day as PETinterim and PETpost, wherever feasible.
All eligible patients will be scanned on a 3T Magnetom Skyra by Siemens, which is a dedicated MRI radiotherapy simulator at Liverpool Cancer Therapy Centre (LCTC). Sequences will be acquired with 3mm slice thickness in the radiotherapy position using a surface coil. The field of view should include the primary as a priority, and include regional nodes if applicable.
Patients should receive a single bolus of IV 20mg prior to scanning to reduce motion artefact. If the patient has a contraindication to hyoscine butylbromide and is not diabetic, glucagon can be used as an alternate agent. The MRI scan can proceed without either agent if both are contraindicated.
Sequences to be acquired:
-T1 axial (for bone fusion with CT)
-T2 axial, sagittal, oblique axial (perpendicular to primary tumour), oblique sagittal
(longitudinal to primary tumour)
-DWI with B-values 50, 400 and 800

Detection of HPV 16 and 18 viral DNA is detected and quantified from the patient’s plasma through a droplet digital polymerase chain reaction (ddPCR) test. This is referred to as circulating tumour DNA in this instance, as the HPV DNA is integrated into the tumour cells.
Collection of peripheral blood is required for HPV ctDNA testing. The baseline sample should be collected no more than 4 weeks prior to commencement of CRT. Blood will be collected and analysed 2 weeks into CRT, and 3 months after completion of CRT. To minimise additional venepuncture for patients, blood will be collected at the time of cannulation for either PET (in the nuclear medicine department at Liverpool Hospital) or CT scanning (Liverpool or Campbelltown Cancer Therapy Centres), wherever this is possible.
Intervention code [1] 326994 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 336065 0
Locoregional failure will be assessed by using FDG PET, MRI imaging and HPV ctDNA biomarker testing.
Timepoint [1] 336065 0
6 months post chemoradiation treatment
Primary outcome [2] 336066 0
MTV 2.5 will be assessed using FDG-PET imaging.
Timepoint [2] 336066 0
2 weeks during chemoradiation treatment, 3 and 6 months post chemoradiation treatment
Primary outcome [3] 336067 0
Diffusion weighted images with B values 50, 400 and 800 will be assessed using MRI
Timepoint [3] 336067 0
2 weeks during Chemoradiation treatment
Secondary outcome [1] 426723 0
Quantification of HPV ctDNA assessed by blood sample analysis
Timepoint [1] 426723 0
2 weeks during chemoradiation treatment, 3 and 6 months post chemoradiation treatment
Secondary outcome [2] 427051 0
Volumetric changes indicating progression free survival i.e <30% increase in volume as per RECISTS1.1 using FDG-PET and MRI imaging
Timepoint [2] 427051 0
2 weeks during chemoradiation and 3 and 6 months post chemoradiation

Eligibility
Key inclusion criteria
- Age greater than or equal to 18
- Patient willing and able to give written informed consent
- Patient deemed suitable for CRT treatment protocol as determined by both a medical oncologist and a radiation oncologist
- Biopsy confirming histological diagnosis of primary invasive anal squamous cell carcinoma, and documentation of p16 immunohistochemistry status
- TNM stage T1-T4 N0-N1 M0 (AJCC 8th edition), determined by
-Clinical groin examination
-DRE
-EUA or anoscopy- CT chest, abdomen and pelvis (with IV contrast unless contraindicated)
-Documentation of size of primary lesion
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Women lactating, pregnant or of childbearing potential with inadequate contraception
- Patients who have previously received systemic therapy for anal cancer, or previous radiotherapy to the pelvis
- Previous HPV-related malignancy within the last 3 years
- Macroscopic surgical resection of the primary anal cancer
- P16 negative on immunohistochemical staining (note: equivocal staining pattern not an exclusion)
- ECOG performance status >2
- Patients with significant medical or psychosocial conditions that may impact their ability to understand or complete the treatment protocol and study requirements
- Distant metastatic disease (M1)
If enrolled into the MRI sub-study:
- Inability to have an MRI due to severe claustrophobia, implanted incompatible devices (including pacemakers and implantable defibrillators) or magnetic material (e.g. bullet shrapnel, intraocular metal).

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
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2023
Actual
Date of last participant enrolment
Anticipated
1/06/2026
Actual
Date of last data collection
Anticipated
1/12/2028
Actual
Sample size
Target
28
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 25512 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 41331 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 314797 0
Hospital
Name [1] 314797 0
Liverpool Hospital, Radiation Oncology Department
Country [1] 314797 0
Australia
Primary sponsor type
Government body
Name
South Western Sydney Local Health District
Address
Administration Building, Eastern Campus, Liverpool Hospital Locked Bag 7279, Liverpool BC 1871
Country
Australia
Secondary sponsor category [1] 316787 0
None
Name [1] 316787 0
Address [1] 316787 0
Country [1] 316787 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313809 0
South Western Sydney Local Health District
Ethics committee address [1] 313809 0
Administration Building, Eastern Campus, Liverpool Hospital Locked Bag 7279, Liverpool BC 1871
Ethics committee country [1] 313809 0
Australia
Date submitted for ethics approval [1] 313809 0
02/08/2023
Approval date [1] 313809 0
20/09/2023
Ethics approval number [1] 313809 0

Summary
Brief summary
This study aims to investigate whether the combination of FDG-PET imaging, MRI scans and blood sampling will lead to more accurate assessment of anal cancer location and progression.

Who is it for?
You may be eligible for this study if you are aged 18 years or older, you have been diagnosed with anal cancer (specifically, anal squamous cell carcinoma) and your doctor has determined that chemoradiation therapy would be a suitable treatment option for you.

Study details
All participants who choose to enrol in this study will be asked to provide up to 3 blood samples which will be tested for cancer markers. Participants will also be asked to undergo a form of imaging called FDG-PET scanning which will involve injection of a dye prior to the scan. It is anticipated that completion of the scan and blood samples will take no more than 2 hours. Participants will be asked to complete 1 FDG-PET scan prior chemoradiotherapy, 1 FDG-PET throughout the course of their chemoradiotherapy which is usually delivered over 5-6 weeks and maximum of 2 FDG PET post chemoradiotherapy.
A small group of participants who agree to participate in an additional sub-study will also be asked to undergo up to 3 MRI scans to look for additional cancer markers. Overall participation will not exceed 30 months after enrolment into the study.

It is hoped that the findings from this investigations will provide new cancer markers that can be used to determine how well patients with anal cancer are responding to chemoradiation treatment. If this study finds new markers that look promising, these may be used to guide treatment decisions and could lead to improved outcomes for patients with anal cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129414 0
Mr Mark Lee
Address 129414 0
Liverpool Cancer Therapy Centre, Locked Bag 7103, Liverpool BC, NSW 1871, Australia
Country 129414 0
Australia
Phone 129414 0
+61 2 87389806
Fax 129414 0
Email 129414 0
[email protected]
Contact person for public queries
Name 129415 0
Penny Phan
Address 129415 0
Radiation Oncology Clinical Trials, 1 Campbell St, Liverpool NSW, 2170
Country 129415 0
Australia
Phone 129415 0
+61 429094402
Fax 129415 0
Email 129415 0
[email protected]
Contact person for scientific queries
Name 129416 0
Penny Phan
Address 129416 0
Radiation Oncology Clinical Trials,, 1 Campbell St, Liverpool NSW, 2170
Country 129416 0
Australia
Phone 129416 0
+61 429094402
Fax 129416 0
Email 129416 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
Data will be analysed to seek correlations and trends. Results will be presented as a whole.


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.