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Trial registered on ANZCTR


Registration number
ACTRN12617001642370
Ethics application status
Approved
Date submitted
28/09/2017
Date registered
19/12/2017
Date last updated
2/05/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A study looking at the use of Mfolfirinox Chemotherapy And Stereotactic Radiotherapy for Patients with Locally Advanced pancreatic cancer to evaluate if this is a feasible treatment option with acceptable acute toxicity rates.
Scientific title
Mfolfirinox And STEreotactic Radiotherapy for Patients with Locally Advanced paNcreatic cancer (MASTERPLAN): a feasibility study to assess if mFOLFIRINOX chemotherapy and Stereotactic Body Radiation Therapy (SBRT) is a feasible neoadjuvant treatment option with acceptable acute toxicity rates for patients with Borderline Resectable Pancreatic Adenocarcinoma (BRPC) or Unresectable Pancreatic Adenocarcinoma (UPC)
Secondary ID [1] 292975 0
Nil
Universal Trial Number (UTN)
U1111-1202-7476
Trial acronym
MASTERPLAN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Borderline Resectable Pancreatic Adenocarcinoma 304876 0
Unresectable Pancreatic Adenocarcinoma 305317 0
Condition category
Condition code
Cancer 304188 304188 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention involved in this study are;
- four cycles of mFOLFIRINOX chemotherapy (standard of care). This involves Oxaliplatin (75mg/m2) via intravenous administration, Irinotecan(150mg/m2) via intravenous administration, 5-fluorouracil (2400mg/m2) via continuous infusion over 4 days. This is done 4 times every 14 days. The chemotherapy is prescribed by a qualified medical oncologist and delivered by a qualified registered nurse.
- insertion of fiducial markers used for imaging during radiotherapy which is performed more than 3 days before the commencement of SBRT. Fiducial markers that aid in the visualisation of the tumour during radiotherapy will be inserted prior to SBRT. The fiducial markers will be placed either percutaneously (needle puncture of the skin), intraoperatively (during surgery), or under Endoscopic ultrasound (EUS) guidance. The method used will depend on tumour location. This only needs to be performed at one time point. This will take approximately 30 minutes to complete.
- SBRT will follow the completion of the four cycles of mFOLFIRINOX chemotherapy, SBRT will commence 2-4 weeks following the completion of mFOLFIRINOX chemotherapy based on clinician discretion. SBRT involves 5 treatments given over 2 to 3 weeks (depending on machine availability) to a dose of 30-45Gy. Patients are permitted to have treatment on two consecutive days but not three. Each SBRT treatment will take approximately 30 to 40 minutes each session. Dose per fraction will be 6 to 9Gy pending the location of the tumour. SBRT is prescribed by a qualified radiation oncologist and the SBRT is delivered by a qualified radiation therapist.
- surgery (if cancer is resectable after chemotherapy and SBRT),
- study blood tests. Study blood tests will be performed at baseline prior to chemotherapy, prior to cycle 2 , 3 and 4 of chemotherapy, prior to SBRT, 4 weeks following SBRT and at 3, 6, 12, 18 and 24 months following SBRT. These tests will require 35ml of blood to be taken (just over two tablespoons of blood).
- Positron Emission Tomography (PET) imaging using 18F-MISO and 18FDG-PET (approximately 4 hours each), The PET scans (both the 18F-MISO and FDG-PET) involves the use of an intravenously administered radioactive drug (tracer) followed by the scan. The PET-CT scan will be performed by a suitably qualified allied health professional. The 18FDG-PET is performed at baseline as standard of care and the performed as a study procedure prior to SBRT and 4 weeks after completion of SBRT. The 18F-MISO PET is completed only as a study procedure at baseline, prior to SBRT and 4 weeks after completion of SBRT if available.
- Magnetic Resonance Imaging (MRI). The MRI scans will be performed before and in the follow up stage after radiotherapy treatment over approximately a 24 month period. This includes MRI scans performed at least one week prior to radiotherapy treatment, and then 3, 6, 12, 18 and 24 months after radiotherapy treatment is finished. ALL MRI scans performed before or after the radiotherapy treatment are for the assessment of tumour and treatment response. The MRI scans will involve the use of a contrast agent administered intravenously by the treating doctor, unless contraindicated then no contrast will be used. The MRI scan will be performed by a suitably qualified allied health professional.
- completion of quality of life (QoL) questionnaires. QoL questionnaires will be completed by the participant at baseline, prior to SBRT, 6 weeks after SBRT, 3 months after SBRT and 6 months after SBRT. Subsequently QOL will be completed 6 monthly up until and including the 18 month follow up appointment.

The use of mFOLFIRINOX chemotherapy and SBRT in isolation has been tested but this study is testing the feasibility when they are combined.

For the investigational PET imaging and MRI scans performed at baseline, prior to SBRT and 4 weeks following SBRT, these will be performed within a few days of each other at the same hospital but in different departments. All investigational blood tests will be performed on the same day as the routine clinic visit.
The clinical trials team will document compliance of attendance at scheduled imaging. Patients who have not attended their scheduled imaging will be contacted by the clinical trials team and reasons for failure to attend will be sought. Where possible, attendance to reschedule appointments will be facilitated.
Intervention code [1] 299220 0
Treatment: Other
Comparator / control treatment
No control group - all patients will receive the same investigations.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 303502 0
To assess if mFOLFIRINOX chemotherapy and SBRT is a feasible neoadjuvant treatment option with acceptable acute toxicity rates for patients with BRPC or UPC.
This will be assessed by the EORTC QLQ-C30 and PAN26 QoL and toxicity data as per CTCAE V4 criteria.
Timepoint [1] 303502 0
6 weeks following completion of SBRT and then 3 monthly following SBRT for 1 year then 6 monthly for another year,
Secondary outcome [1] 339087 0
Response rates with neoadjuvant mFOLFIRINOX and SBRT as per RECIST criteria.
Timepoint [1] 339087 0
6 weeks following completion of SBRT and then 3 monthly following SBRT for 1 year then 6 monthly for another year,
Secondary outcome [2] 339088 0
Acute and late side effects with neoadjuvant mFOLFIRINOX and SBRT. Known side effects from mFOLFIRINOX include include gastrointestinal, neurological, myelosuppression, cutaneous manifestations and death. Known acute side effects from SBRT include nausea, vomiting, fatigue, gastritis, weight loss, anorexia and diarrhoea and know late side effects include haemorrhage, gastritis, ulceration, perforation, obstruction, gastroparesis and pancreatic insufficiency. All toxicity will be assessed using CTCAE version 4.
Timepoint [2] 339088 0
6 weeks following completion of SBRT and then 3 monthly following SBRT for 1 year then 6 monthly for another year,
Secondary outcome [3] 339090 0
Margin negative resection rates after neoadjuvant mFOLFIRINOX and SBRT
Timepoint [3] 339090 0
Margin negative resection rate is determined from pathology specimen with margin >1mm considered to be a negative resection margin. This is assessed directly from the pathology report following surgery.
Secondary outcome [4] 339091 0
1 year disease-free survival rates after neoadjuvant mFOLFIRINOX and SBRT. This will be assessed by clinical assessment.
Timepoint [4] 339091 0
12 months following completion of SBRT.
Secondary outcome [5] 339092 0
Assess qualitatively the functional Magnetic Resonance Imaging (MRI) changes of the pancreas at different time points during neoadjuvant treatment with mFOLFIRINOX and SBRT
Timepoint [5] 339092 0
Prior to SBRT and 4 weeks following completion of SBRT
Secondary outcome [6] 339095 0
Assess the variation in position of fiducial markers inserted into the pancreas during a course of SBRT
Timepoint [6] 339095 0
During SBRT treatment delivery via imaging modalities on the treatment machine including 4D cone beam CT at every fraction of SBRT.
Secondary outcome [7] 339096 0
Assess the changes in 18FDG uptake in patients diagnosed with pancreatic adenocarcinoma receiving mFOLFIRINOX and SBRT
Timepoint [7] 339096 0
Prior to any treatment, prior to SBRT and 4 weeks following completion of SBRT via measurement of total lesional glycolysis (TLG) and maximum standardised uptake value (SUV).
Secondary outcome [8] 339097 0
Assess the changes in tumour hypoxia in patients diagnosed with pancreatic adenocarcinoma receiving mFOLFIRINOX and SBRT
Timepoint [8] 339097 0
Prior to any treatment, prior to SBRT and 4 weeks following completion of SBRT via measurement of maximum SUV.
Secondary outcome [9] 340267 0
Treatment completion rates with neoadjuvant mFOLFIRINOX and SBRT
Timepoint [9] 340267 0
At the completion of neoadjuvant mFOLFIRINOX and SBRT.
Secondary outcome [10] 340268 0
1 year overall survival rates after neoadjuvant mFOLFIRINOX and SBRT. This will be assessed by clinical assessment.
Timepoint [10] 340268 0
12 months following completion of SBRT.
Secondary outcome [11] 341220 0
2 year disease-free survival rates after neoadjuvant mFOLFIRINOX and SBRT. This will be assessed by clinical assessment.
Timepoint [11] 341220 0
24 months following completion of SBRT.
Secondary outcome [12] 341221 0
2 year overall survival rates after neoadjuvant mFOLFIRINOX and SBRT. This will be assessed by clinical assessment.
Timepoint [12] 341221 0
24 months following completion of SBRT.

Eligibility
Key inclusion criteria
Age greater than or equal to 18 years and able to give informed consent.
Patients with histologically confirmed adenocarcinoma of the pancreas that is classified as BRPC or UPC, as per NCCN guidelines.
ECOG performance status 0 or 1.
Adequate bone marrow function (absolute neutrophil count ((ANC) greater than 1.5, platelets greater than 100).
Adequate liver function (albumin greater than 25 g/L, bilirubin less than or equal to 26 micromol/L; transaminases (ALT/AST) less than or equal to 5 times the upper limit of normal (ULN)).
Adequate renal function (creatinine less than or equal to 1.5 times the ULN).
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Age 70 years and over.
Patients with resectable or metastatic pancreatic cancer.
Neuroendocrine pancreatic carcinoma.
Previous chemotherapy or abdominal radiotherapy.
Previous diagnosis of cancer within the last 5 years (excluding non-melanoma skin cancers, and carcinoma in situ).
Chronic diarrhoea or peripheral neuropathy equal to or greater than grade 2.
Pregnancy.
Non-controlled coronary artery disease or myocardial infarction within the last 6 months.
Known hypersensitivity to 5-fluorouracil, irinotecan, oxaliplatin, capecitabine.
Patient will be ineligible for fMRI if they have contraindication to MRI. They will still have other imaging performed (18FDG-PET and 18F-MISO).
Patients with portal hypertension, coagulopathy or an inaccessible portal vein will not have portal vein blood sampling done as part of CTC/cPSC sub-study.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
This feasibility study is only recruiting 10 participants who will all receive the mFOLFIRINOX and SBRT. There is no randomisation. No statistical justification of patient numbers has been undertaken.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 9108 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 9109 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [3] 9110 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment postcode(s) [1] 17608 0
2170 - Liverpool
Recruitment postcode(s) [2] 17609 0
2560 - Campbelltown
Recruitment postcode(s) [3] 17610 0
2200 - Bankstown

Funding & Sponsors
Funding source category [1] 297601 0
Hospital
Name [1] 297601 0
Liverpool Cancer Services Trust Fund
Address [1] 297601 0
1 Elizabeth St, Liverpool NSW 2170
Country [1] 297601 0
Australia
Primary sponsor type
Hospital
Name
Liverpool Hospital
Address
1 Elizabeth St, Liverpool NSW 2170
Country
Australia
Secondary sponsor category [1] 296615 0
Individual
Name [1] 296615 0
Dr Andrew Oar
Address [1] 296615 0
Liverpool Cancer Therapy
Liverpool Hospital
1 Campbell St Liverpool
NSW 2170
Country [1] 296615 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298694 0
South Western Sydney Local Health District
Ethics committee address [1] 298694 0
Research and Ethics Office
Locked Bag 7103
Liverpool BC
NSW 1871
Ethics committee country [1] 298694 0
Australia
Date submitted for ethics approval [1] 298694 0
21/08/2017
Approval date [1] 298694 0
03/10/2017
Ethics approval number [1] 298694 0

Summary
Brief summary
This study will qualitatively and quantitatively assess MRI and PET (18F-MISO and if available, 18FDG-PET) for the treatment response assessment of pancreatic cancer patients treated using mFOLFIRINOX chemotherapy (which is the current standard of care for chemotherapy) combined with SBRT. The feasibility of the combination of these two therapies will be assessed according to acceptable toxicity rates.
Who is it for?
You may be eligible to join this study if you are aged 18 years to 69 years and have been diagnosed with borderline resectable pancreatic adenocarcinoma or unresectable pancreatic adenocarcinoma.

Study details:
All patients who are enrolled in the study will receive the standard pre-treatment work-up, study treatment of mFOLFIRINOX chemotherapy combined with SBRT and post treatment surveillance. In addition patients will be subjected to 3 additional MRIs, 2 two additional 18FDG-PET and 3 additional 18F-MISO PET (if available) conducted up to 4 weeks following completion of SBRT. Patients will also be subjected to study blood tests. Some blood tests may be part of standard care but those that are not will be included with the standard of care blood tests with additional blood taken and if not part of standard collection, will be taken at the correct timepoint for the study. Patients will be asked to complete QoL questionnaires at 7 timepoints throughout the study.
Those patients that are determined to have resectable cancer by the multidisciplinary team following their treatment will proceed to surgical removal of their tumour. Follow up will continue on patients who have resectable or unresectable cancer for 24 months following treatment.
This study will inform the design of a larger, randomised, multicentre trial.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes

Contacts
Principal investigator
Name 77914 0
Dr Mark Lee
Address 77914 0
Liverpool Cancer Therapy Centre,
Locked Bag 7103
Liverpool BC
1871 NSW
Country 77914 0
Australia
Phone 77914 0
+61 2 8738 9806
Fax 77914 0
+61 2 8738 9811
Email 77914 0
mark.lee2@health.nsw.gov.au
Contact person for public queries
Name 77915 0
Dr Andrew Oar
Address 77915 0
Liverpool Cancer Therapy Centre,
Locked Bag 7103
Liverpool BC
1871 NSW
Country 77915 0
Australia
Phone 77915 0
+61 2 8738 9806
Fax 77915 0
+61 2 8738 9811
Email 77915 0
Andrew.Oar@health.nsw.gov.au
Contact person for scientific queries
Name 77916 0
Dr Andrew Oar
Address 77916 0
Liverpool Cancer Therapy Centre,
Locked Bag 7103
Liverpool BC
1871 NSW
Country 77916 0
Australia
Phone 77916 0
+61 2 8738 9806
Fax 77916 0
+61 2 8738 9811
Email 77916 0
Andrew.Oar@health.nsw.gov.au

No data has been provided for results reporting
Summary results
Not applicable