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Trial registered on ANZCTR


Registration number
ACTRN12617001571369
Ethics application status
Approved
Date submitted
12/09/2017
Date registered
22/11/2017
Date last updated
22/11/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Stereotactic ablative body radiotherapy for Unresectable Pancreatic cancer with Endoscopic ultrasound inserted fiducial markers and concuRrent chemotherapy (SUPER) trial.
Scientific title
Effect of Stereotactic ablative body radiotherapy for Unresectable Pancreatic cancer with Endoscopic ultrasound inserted fiducial markers and concuRrent chemotherapy on survival rates: SUPER trial.
Secondary ID [1] 292478 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic cancer tumours 304099 0
Condition category
Condition code
Cancer 303434 303434 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Stereotactic ablative body radiotherapy for Unresectable Pancreatic cancer with Endoscopic ultrasound inserted fiducial markers and concuRrent chemotherapy (SUPER) trial.
All aspects of this study will be discussed with each patient during the recruitment process. An information sheet will be provided, and each patient will be given the opportunity to discuss this study will a medical practitioner, friends or family prior to involvement. Each participant will give written, informed consent and will be free to withdrawal from the study at any time.
This would start to assess the safety and outcome of combined FOLFIRINOX chemotherapy and stereotactic radiotherapy guided by EUS inserted fiducial markers in locally advanced PDAC. If the approach is deemed safe, we will then apply for a further ethics submission to perform a multi-centre, randomized control trial looking at SBRT combined with chemotherapy versus chemotherapy alone. This would involve patients with locally advanced disease, deemed as either unresectable or borderline resectable.
In this study, all patients who are deemed to have inoperable pancreatic cancer from assessment of a multi-disciplinary team (combined hepato-biliary surgery, radiation oncology and medical oncology), and planned for treatment with combined chemoradiotherapy will be recruited.

Patients receive a FOLFIRINOX based regime given over a 4 month period (oxaliplatin, irinotecan, leucovorin, fluorouracil every 2 weeks, totaling 8 cycles). This is followed by 2 weeks of Capecitabine as a radio-sensitizer (850 mg/m2 twice daily for 5 days of each week (Monday to Friday)), then followed by fiducial guided SBRT (25Gy in 5 fractions delivered to gross tumour and simultaneous integrated boost of 35Gy in 5 fractions to region of vessel encasement).
The dose of each of the drugs in the FOLFINIROX based regime will be variable (as determined by treating physician), and mode of administration will be IV. The drugs for the FOLFIRINOX based regime will be given simultaneously. The mode of administration for capecitabine will be oral tablet.
Patients to undergo the following tests before treatment:
1. bMRI abdomen and/or whole body PET scan
2. Bilirubin
3. Liver function
4. CA 19.9 and CE
5. Complete blood examination
Four gold fiducials will be placed by EUS guidance in 4 quadrants of the pancreatic mass to outline its peripheral borders, using a specifically designed 22G EchoTip Fiducial needle.
CT simulation will be performed within 5 days after fiducial placement. Before simulation, patients will commence a low residue diet, fast for 6 hours prior and may require appropriate analgesia depending on level of patient discomfort. Simulation will employ full body immobilization (Omni V SBRT system), multidetector 4DCT with 3mm slices and IV contrast (late arterial phase scan). Patient to be positioned supine with arms raised above the head. Simulation tumour motion study to be assessed to determine the degree of tumour excursion. For target displacement of >5mm, consideration to be given to abdominal compression to address the issue of movement at the oncologists discretion. Scan limits are from nipple to umbilical level. Reference tattoos to be used.
The duration of the fiducial placement will be 5 minutes, CT simulation will be for 15 minutes, and fiducial guided SBRT will be for 90 minutes.
Treatment planning will require MRI and/or PET fusion to ensure accurate delineation of the target volume on the 4DCT maximum intensity projection. Organ at risk and radiotherapy plan to be generated from the 4DCT average scan. SBRT will be scheduled to commence within 2 weeks.
Treatment delivery will be in 5 fractions, with a maximum of 2 fractions per week at least 48 hours apart. Patient to be pretreated with oral dexamethasone 4mg and Ondansetron 8mg, approximately 1 hour prior to treatment. Consideration to be given to pretreatment Paracetamol 1g and Lorazepam 1mg, if the patient is in pain or anxious, respectively.
Patients will require the same full body immobilization as determined at time of CT simulation. The linear accelerator will have high definition multileaf collimators and cone beam CT technology available. An onboard image match to be carried out for bone alignment followed by a pretreatment cone beam CT scan. An online image matching process of the gold seed fiducial markers to the reference image will be carried out. Exportation of the duodenal region of interest will aid in online matching. The tolerance for treatment couch shift based on cone beam CT is 0mm and for repeat cone beam CT acquisition this will be 3mm.
For biomarker applications, sections of cell-block material from the resected specimens of the patients receiving fiducial guided radiochemotherapy, will be assessed for S100A2 and S100A4 expression using immunohistochemistry. Serum levels or CA 19-9 (Carbohydrate antigen 19-9) and CEA (Carcinoembryonic Antigen) will also be measured.
Intervention code [1] 299164 0
Treatment: Devices
Intervention code [2] 299310 0
Treatment: Drugs
Comparator / control treatment
Patients receive a FOLFIRINOX based regime given over a 4 month period (oxaliplatin, irinotecan, leucovorin, fluorouracil every 2 weeks, totaling 8 cycles).

Dose of each of the drugs in the FOLFINIROX based regime will be variable, as determined by treating physician, and mode of administration will be IV.
Control group
Active

Outcomes
Primary outcome [1] 302865 0
To determine and compare the survival rates of patients recieving chemotherapy alone with fiducial guided stereotactic radio-chemotherapy. This will be assessed via medical records and contact with the patient.
Timepoint [1] 302865 0
The survival outcomes will be collected at 3, 6, 9 and 12 months after the completion of treatment.
Primary outcome [2] 302866 0
To determine and compare the resectability rates of patients recieving chemotherapy alone with fiducial guided stereotactic radio-chemotherapy. This will be assessed via medical records and contact with the patient.
Timepoint [2] 302866 0
Restaging CT scan to determine suitability for resection to be performed at 4 weeks post completion of stereotactic chemoradiotherapy.
Secondary outcome [1] 337273 0
To determine the technical success of fiducial placement. This is defined as the ability for the fiducial marker to be successfully planted to its target position.

Assessed via medical records and with communication with the oncologists, gastroenterologists, and research fellows.
Timepoint [1] 337273 0
The clinical outcomes will be collected at 3, 6, 9 and 12 months after the completion of treatment.
Secondary outcome [2] 338936 0
To compare pain scores of patients recieving chemotherapy alone with fiducial guided stereotactic radio-chemotherapy. Pain will be assessed via numeric rating scales.
Timepoint [2] 338936 0
Pain scores will be assessed before, at day 0 and 14 during treatment, as well as 1, 3, 6, 9 and 12 months after treatment.
Secondary outcome [3] 338937 0
To compare QOL questionnaires of patients recieving chemotherapy alone with fiducial guided stereotactic radio-chemotherapy.
Timepoint [3] 338937 0
SF36 QOL questionnaires will be assessed before, at day 0 and 14 during treatment, as well as 1, 3, 6, 9 and 12 months after treatment.
Secondary outcome [4] 338938 0
To assess the safety of combined FOLFIRINOX chemotherapy and stereotactic radiotherapy guided by EUS inserted fiducial markers in locally advanced PDAC. Participants will be monitored for any adverse events following procedures in the following ways:
-2 hour observation period in our recovery area, where patient vitals and symptoms (such as abdominal pain) will be recorded
-regular follow up in outpatient clinics

Possible adverse events include: abdominal pain, pancreatitis, fever, bleeding. perforation
Timepoint [4] 338938 0
All participants will also be monitored for safety for up to 7 days post procedure. And by checking medical records over the next 12 months.

Eligibility
Key inclusion criteria
1. Histologically or cytologically confirmed adenocarcinoma of the pancreas.

2. Locally advanced disease, which is deemed:
a) Unresectable; or
b) Borderline resectable , which includes these tumour characteristics:
(i) - involvement of superior mesenteric or portal vein but with sufficient vessel proximal and distal to the area of vessel involvement (which allows safe resection and reconstruction)
(ii) - gastroduodenal artery encasement up to the hepatic artery and involvement of the hepatic artery without extension to the celiac axis
(iii) - superior mesenteric artery involvement less than 180 degrees

3. Patients should have a projected life expectancy of at least 6 weeks

4. ECOG performance status less than or equal to 2

5. 18 years old or older

6. Measurable disease as defined by RECIST 1.1.

7. Serum bilirubin less than 30 µmol/L, after successful biliary decompression with stents

8. Adequate bone marrow function, WCC greater than 3 x 10^9/L, platelets greater than100 x 10^9/L

9. Written informed consent

10. Those deemed for combined chemoradiotherapy as per multi-disciplinary team consensus
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Metastatic disease from pancreatic cancer

2. Prior chemotherapy or radiotherapy

3. History of other malignant diseases other than non-melanomatous skin cancer or in-situ carcinoma of the uterine cervix

4. Clinical evidence of uncontrolled angina pectoris, cardiac failure, clinically significant cardiac arrhythmia, or other serious uncontrolled medical condition

5. Pregnant or lactating (any woman of childbearing potential must have a pregnancy test prior to randomization and must take adequate precautions to prevent pregnancy during treatment)

6. Tumour size greater than 75mm

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2017
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
250
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 297049 0
Hospital
Name [1] 297049 0
Royal Adelaide Hospital
Country [1] 297049 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000
Country
Australia
Secondary sponsor category [1] 296052 0
None
Name [1] 296052 0
n/a
Address [1] 296052 0
n/a
Country [1] 296052 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298230 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 298230 0
Ethics committee country [1] 298230 0
Date submitted for ethics approval [1] 298230 0
Approval date [1] 298230 0
23/12/2015
Ethics approval number [1] 298230 0

Summary
Brief summary
This study will determine the effect of stereotactic ablative body radiotherapy (SBRT) with endoscopic ultrasound inserted fiducial markers for unresectable pancreatic cancer.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above, have adenocarcinoma of the pancreas which has been deemed inoperable and are planning for treatment with combined chemotherapy.

Study details
Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will receive chemotherapy only In this trial, patients receive a FOLFIRINOX based regime given over a 4 month period (oxaliplatin, irinotecan, leucovorin, fluorouracil every 2 weeks, totalling 8 cycles). While participants in the other group will receive chemotherapy of Folfirinox based regime and they will also receive 2 weeks of Capecitabine as a radio-sensitizer (850 mg/m2 twice daily for 5 days of each week (Monday to Friday)), prior to fiducial guided SBRT (25Gy in 5 fractions delivered to gross tumour and simultaneous integrated boost of 35Gy in 5 fractions to region of vessel encasement).
Participants will be followed-up for up to 12 months post-completion of treatment to determine survival rates, resectability rates, technical success of fiducial placement, pain and quality of life.

The use of radiotherapy, either alone or in combined with chemotherapy, has been evaluated in the past but evidence is limited due the lack of ability to deliver the radiation to the pancreatic mass without causing adverse effects to surrounding organs. One of the approaches to overcome this problem is to use marker-guided stereotactic radiotherapy, which is increasingly applied in the field of radiation oncology. The majority of studies have looked at technical success and safety rather than patient survival and quality of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76414 0
Dr Vinh-An Huu
Address 76414 0
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000
Country 76414 0
Australia
Phone 76414 0
+61 8 8222 5214
Fax 76414 0
Email 76414 0
[email protected]
Contact person for public queries
Name 76415 0
Romina Safaeian
Address 76415 0
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000
Country 76415 0
Australia
Phone 76415 0
+61 8 8222 5214
Fax 76415 0
Email 76415 0
[email protected]
Contact person for scientific queries
Name 76416 0
Romina Safaeian
Address 76416 0
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000
Country 76416 0
Australia
Phone 76416 0
+61 8 8222 5214
Fax 76416 0
Email 76416 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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