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Trial registered on ANZCTR


Registration number
ACTRN12616001697471
Ethics application status
Approved
Date submitted
3/11/2016
Date registered
9/12/2016
Date last updated
17/07/2019
Date data sharing statement initially provided
17/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Stereotactic ablative body radiotherapy (SABR) for Liver Cancer After Radiology treatment (TACE)
Scientific title
Fiducial Image guided Stereotactic ablative body radiotherapy (SABR) for Hepatocellular carcinoma After Interventional Radiology treatment (TACE) (FISHAR trial)
Secondary ID [1] 290304 0
None
Universal Trial Number (UTN)
U1111-1188-5494
Trial acronym
FISHAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma 300553 0
Condition category
Condition code
Cancer 300411 300411 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Imaging of patients will be reviewed by investigating EUS Endoscopist and Radiation Oncologist. If required, radiotherapy fiducial markers will be placed by EUS in four quadrants of the ablated site, or surgical margin to outline its peripheral borders. EUS and fiducial placement will be carried out in accordance with Gastroenterology and Hepatology Unit protocol at the Royal Adelaide Hospital. Fiducial insertion will be performed by A/Prof Nam Quoc Nguyen MBBS (Hons) PhD FRACP, Consultant Gastroenterologist/ Interventional Endoscopist at the Royal Adelaide Hospital. The patient is sedated for the procedure which takes approximately 15 minutes to complete.

CT simulation will be performed within five days after fiducial placement. Simulation will employ full body immobilization (Omni V SBRT system), multi-detector 4DCT with 3mm slices and IV contrast (late arterial phase scan). Simulation tumour motion study will be assessed to determine the degree of tumour excursion. Treatment planning is determined by imaging (CT or MRI) to ensure accurate delineation of the target volume on the 4DCT maximum intensity projection. SABR will be scheduled to commence within two weeks from simulation. The planning criteria will be as follows: Planning Target Volumes (PTV): In ablated lesions, PTV will be determined by gross tumour volume (GTV) plus uniform 5mm margin. In resected lesions, PTV will be determined by the clinical target volume (CTV) plus uniform 5mm margin.
The absorbed dose will be 42-45Gy in three fractions to each PTV (BED10 = 100.8Gy). The prescription isodose should encompass at least 95% of the PTV. The maximum dose within the PTV should not exceed 140%. Treatment delivery will be in three fractions, with a maximum of two fractions per week at least 48 hours apart. Online image matching process of the gold seed fiducial markers to the reference image will be carried out.
Follow up: The clinical outcomes of tumour size, AFP and survival will be collected at 1, 3, 6, 9, 12, 18 and 24 months after the completion of treatment. The exact modality of radiological restaging (CT or MRI) will be at the discretion of the HCC MDT, to allow for the best method of assessing efficacy of therapy. Any subsequent therapy due to progression of HCC (if needed), will be determined by the HCC MDT.
To evaluate the feasibility and safety of fiducial marker insertion and SABR on liver disease evident by decompensation of synthetic liver dysfunction or regional toxicity from radiation - weekly blood tests (CBP, EUC, LFT and INR) will be performed from commencement and up to four weeks after completion of SABR, to assess for deterioration of liver impairment/failure. Side effect profile will be carefully documented including any pain, discomfort, nausea or vomiting during or post SABR. Complications related to EUS insertion of fiducials will be recorded, including fiducial migration, bleeding, and organ perforation.

Fiducial markers: endoscopic ultrasound guided insertion of 3 gold markers in the peritumoural region.
SABR: ct simulation takes approximately 45 min to 1 hour. SABR is delivered over 3 fractions at least 48 hours apart. Each fraction takes approximately 30-45 min to complete.

The decision for 42 vs 45Gy is determined at the time of radiotherapy planning. Where the dose can be delivered safely without exceeding the normal tissue constraints, 45Gy in 3 fractions would be choice at the discretion of the radiation oncologist. The timing is a departmental logistical decision. Whilst adhering to the rule of 48 hrs apart and 2 fractions max per week, the logistical capacity of the department to treat is the determining factor regarding exact timing. Exact isodose is determined at planning – this choice is a balance of achieving dose coverage of the tumour target and maintaining a dose max that is within the recommended constraints.
Intervention code [1] 296112 0
Treatment: Devices
Intervention code [2] 296560 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 300046 0
(1) Persistent tumour or local recurrence

Tumour growth characteristics and local recurrence will be determined by using Response Evaluation Criteria In Solid Tumors (RECIST) criteria and imaging studies.
Modalities (CT/MRI) will be determined by the HCC MDT at the Royal Adelaide Hospital.
Timepoint [1] 300046 0
Persistent tumour or local recurrence will be measured at 1, 3, 6, 9, 12, 18 and 24 months after the completion of treatment.
Primary outcome [2] 300190 0
(2) New development of distant metastasis during this study.

Tumour growth characteristics and distal metastasis will be determined by Response Evaluation Criteria In Solid Tumors (RECIST) and imaging studies.
Modalities (CT/MRI) will be determined by the HCC MDT at the Royal Adelaide Hospital.
Timepoint [2] 300190 0
The development of new or distant metastasis will be measured during this study at 1, 3, 6, 9, 12, 18 and 24 months after the completion of treatment.
Secondary outcome [1] 328918 0
(1) Progression of MELD - The Model for End Stage Liver Disease (MELD) will be used to predict survival for patients with advanced liver disease.
Timepoint [1] 328918 0
The progression of MELD will be calculated at 1, 3, 6, 9, 12, 18 and 24 months after the completion of treatment or primary end point is reached.
Secondary outcome [2] 329290 0
(2) Progression of Child’s Pugh Score. The Child-Turcotte-Pugh Classification for Severity of Cirrhosis will be used to estimate the child's cirrhosis severity.
Timepoint [2] 329290 0
The progression of Child’s Pugh Score will be calculated at 1, 3, 6, 9, 12, 18 and 24 months after the completion of treatment or primary end point is reached.

Eligibility
Key inclusion criteria
INCLUSION CRITERIA
Aged > 18 years
Able to give informed consent
ECOG 0-1
Barcelona clinic liver cancer (BCLC) class A/B as determined by a Hepatocellular Carcinoma Multidisciplinary team (HCC MDT)
HCC diagnosed by standard radiological criteria or histology
HCC < 6cm which is amenable to SABR
Pre-treated with TACE with incomplete response or re-occurrence
Measureable disease on imaging defined by M RECIST criteria
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
EXCLUSION CRITERIA
BCLC C (significant decompensated liver disease or HCC not amenable to TACE)
Significant comorbidities unable to safely tolerate sedation/anaesthetic
Expected life expectancy of < 24 months
Prior radiotherapy to abdomen
Pregnant or lactating (any woman of childbearing potential must have a pregnancy test prior to enrollment and must take adequate precautions to prevent pregnancy during treatment)

Study design
Purpose of the study
Treatment
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
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analysis will be carried out using SPSS version 22.0.0 for Windows. Categorical variables will be compared using Chi-square and Fisher’s exact test where appropriate. Quantitative variables will be tested by t-test. Univariate analysis for survival will be performed using the Kaplan Meier method and differences in Kaplan Meier curves will be tested for statistical significance using the log rank test.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/02/2017
Actual
1/03/2017
Date of last participant enrolment
Anticipated
31/12/2017
Actual
29/05/2019
Date of last data collection
Anticipated
31/12/2019
Actual
Sample size
Target
20
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 7048 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 14776 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 294861 0
Hospital
Name [1] 294861 0
Royal Adelaide Hospital
Country [1] 294861 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Royal Adelaide Hospital Port Road Adelaide South Australia 5000
Country
Australia
Secondary sponsor category [1] 293700 0
None
Name [1] 293700 0
None
Address [1] 293700 0
None
Country [1] 293700 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296245 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 296245 0
Royal Adelaide Hospital Port Road Adelaide South Australia 5000
Ethics committee country [1] 296245 0
Australia
Date submitted for ethics approval [1] 296245 0
22/03/2016
Approval date [1] 296245 0
22/06/2016
Ethics approval number [1] 296245 0
HREC/16/RAH/102

Summary
Brief summary
The primary purpose of this trial is to assess the safety and efficacy of stereotactic ablative body radiotherapy (SABR) for liver cancer which has re-occurred or not responded to radiology treatment (TACE).

Who is it for?
You may be eligible to participate in this trial if you are aged 18 or over and have been diagnosed with hepatocellular carcinoma (liver cancer), which has been pre-treated with TACE with incomplete response or re-occurrence, and is deemed suitable for SABR therapy by your treating clinicians.

Study details
All participants enrolled in this trial will receive SABR therapy. The treating team of clinicians may determine that it would be useful to insert fiducial markers in some participants, which are small gold markers, inserted around the tumour to act as a reference point across different images. Within 5 days of fiducial marker insertion (where applicable), all participants will undergo a CT scan simulating the body immobilisation procedure. This will take approximately 45 minutes to one hour. A full body immobilisation system is utilised to create an impression of the body. The CT scan is more in depth than a regular CT and takes multiple images. Small tattoos are drawn onto the patient to act as a guide to allow the lasers to line up during treatment. In order to help the patient stay still and breathe regularly, they are asked to breathe in time with a metronome (typically 30 bpm). Participants will then undergo three SABR treatment sessions over the next two to three weeks, which involves delivery of radiotherapy to the tumour. The treatment takes approximately one hour and consists of using the full body immobilisation system and the tattoo guides to ensure the patient is in the correct position and alignment for the precise delivery of radiation to the tumour. A quick scan is then done to check the positioning, followed by a more in depth CT scan to verify this. When the treating team are happy with the positioning, the treatment radiation dose will be delivered, followed by a pause mid treatment to verify and confirm the positioning once again.

Post treatment all participants will be followed up every few months for up to 24 months following completion of SABR treatment. This will involve blood tests, CT/MRI scans to assess tumour progression, and monitoring of the side effects related to SABR treatment.

It is hoped that the findings from this trial will provide information on whether SABR, with or without fiducial maker insertion, is safe and effective for the treatment of liver cancer, where the tumours have not responded or re-occurred following treatment with TACE.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
N/A
Attachments [1] 1216 1216 0 0
/AnzctrAttachments/371631-FISHAR Protocol V2.1 September 2016.pdf (Protocol)
Attachments [2] 1217 1217 0 0
/AnzctrAttachments/371631-FISHAR PICF V2.0 June 2016.pdf (Participant information/consent)

Contacts
Principal investigator
Name 69582 0
Dr Hien Le
Address 69582 0
Royal Adelaide Hospital, Radiation Oncology. Port Road Adelaide South Australia 5000.
Country 69582 0
Australia
Phone 69582 0
+61 8 7074 2432
Fax 69582 0
Email 69582 0
[email protected]
Contact person for public queries
Name 69583 0
Erin McCartney
Address 69583 0
Royal Adelaide Hospital, Hepatology. 5E291. Port Road Adelaide South Australia 5000.
Country 69583 0
Australia
Phone 69583 0
+618 70742191
Fax 69583 0
Email 69583 0
[email protected]
Contact person for scientific queries
Name 69584 0
Erin McCartney
Address 69584 0
Royal Adelaide Hospital, Hepatology. 5E291. Port Road Adelaide South Australia 5000.
Country 69584 0
Australia
Phone 69584 0
+618 870742191
Fax 69584 0
Email 69584 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
Chief investigator undecided if IPD will be available.


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.