MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease
MASTERPLAN
MASTERPLAN: A Randomised Phase II Study of MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease
1 other identifier
interventional
120
1 country
11
Brief Summary
This is a prospective, multicentre randomised, phase II clinical trial, with randomisation 2:1 by minimisation and stratification by tumour stage, planned chemotherapy and institution.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 pancreatic-cancer
Started Oct 2019
Typical duration for phase_2 pancreatic-cancer
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 4, 2019
CompletedFirst Posted
Study publicly available on registry
September 13, 2019
CompletedStudy Start
First participant enrolled
October 1, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
August 30, 2023
CompletedOctober 22, 2021
October 1, 2021
3.6 years
February 4, 2019
October 15, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Locoregional control (Locoregional Response Rate LRR)
To determine if the addition of SBRT to chemotherapy improves locoregional control;
Within 12 months of randomisation;
Secondary Outcomes (10)
Safety (NCI CTCAE v5.0)
Safety Assessment before each cycle of chemotherapy, post chemotherapy treatment, following SBRT and surgery (if applicable) then at 3, 6, 9 and 12 months post-randomisation and 6 monthly during year 2, 3 and 4
Surgical morbidity/mortality (Clavien grading system)
At discharge post-surgery, 30 days and 90 days post surgery, up to 4 years
Radiological response rates (RECIST v1.1)
at baseline. In SBRT arm, post-initial chemotherapy (prior to SBRT). In both arms, 4-6 weeks post completion of initial treatment (prior to surgery), 3 ,6, 9 and 12 monthly during year 2, 3 and 4.
Progression Free Survival (PFS) (RECIST v1.1)
From randomisation to the time of first documented clinical or imaging relapse or date of death from any cause, whichever occurs first; up to 4 years
Pathological response rates (College of American Pathology Tumour Regression Grade TRG)
At SRBT/surgery compared to baseline;
- +5 more secondary outcomes
Other Outcomes (3)
Exploratory biomarker analysis of blood
baseline, prior to SBRT (Arm B only), insertion of fiducial markers (Arm B, optional), post initial treatment, at surgery (optional, at selected sites), 6 and12 months post randomisation and at progression, up to 5 years
Exploratory biomarker analysis of tissue
Diagnosis (archival tissue), at time of fiducial insertion (Arm B, optional), surgical resection (for resectable patients) and at time of progression (optional), up to 5 years.
ePRO Acceptability
Baseline, Day 1 of each cycle of chemotherapy, 2 weeks post initial chemotherapy(SBRT arm), 4-6 weeks post initial chemotherapy +/- SBRT, 30 days post end of treatment, at months 3, 6,9 and 12 post randomisation 6 monthly in years 2, 3 and 4.
Study Arms (2)
Arm A
ACTIVE COMPARATOR* Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine
Arm B
EXPERIMENTAL* Option 1: fluorouracil(5-FU)/leucovorin/irinotecan/oxaliplatin (mFOLFIRINOX) (6 cycles) * Option 2: gemcitabine + nab-paclitaxel (3 cycles) * Stereotactic Radiotherapy (SBRT) to commence within 3 weeks of completing initial chemotherapy: 40 Gray (Gy) in 5 fractions over 2 weeks * Resectable patients receive surgery 6 weeks post completion of initial chemotherapy * Unresectable patients continue with ongoing chemotherapy (option 1 or option 2) * Unresectable patients with locoregional progression or metastatic disease, chemotherapy treatment at the discretion of treating medical oncologist * Adjuvant chemotherapy for resectable patients to begin within 8 weeks after surgery * For patients who received option 1 chemotherapy: 12 weeks of mFOLFIRINOX * For patients who received option 2 chemotherapy: 12 weeks of mFOLFIRINOX or 12 additional weeks of gemcitabine/capecitabine
Interventions
40 Gray (Gy) in 5 fractions, 2-3 fractions per week over two weeks, 8 Gy per fraction
* Day 1: oxaliplatin 85mg/m2 + irinotecan 150mg/m2 + leucovorin 50mg * 5-FU 2400mg/m2 continuous IV infusion, 46 hour continuous infusion * 14-day cycle, 6 cycles
* Day 1, Day 8 and Day 15 gemcitabine 1000mg/m2 + nab-paclitaxel 125mg/m2 * 28-day cycle, 3 cycles
* Week 1, 2 and 3, qw: 1000 mg/m2 gemcitabine * 21 days continuous: 830 mg/m2 oral capecitabine + 7 days rest * 28-day cycle, 3 cycles
R0 resection. When the tumour is within the head of the pancreas, a standard Whipple's procedure and level 2/3 dissection with modification to obtain margin clearance will be offered. For lesions in the tail, a standard modular resection will be offered.
Eligibility Criteria
You may qualify if:
- Adults, aged between 18-75 years, with histological confirmation of pancreatic adenocarcinoma
- Any of the following
- T3 (tumour \>4 cm)
- Extrapancreatic extension
- Node positive (stage IIB)
- Borderline resectable pancreatic cancer, locally advanced pancreatic cancer
- Measurable disease according to RECIST v1.1
- ECOG performance status 0-1
- Adequate renal and haematological function
- Adequate hepatic function. Defined as bilirubin \<1.5 X ULN (Upper Limit of Normal), AST + ALT \<3.0 X ULN. In patients who have had a recent biliary drainage and whose bilirubin is descending, a value of ≤ 3 X N is acceptable
- Study treatment planned to start within 14 days of registration
- Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
- Signed, written informed consent
You may not qualify if:
- Tumour size greater than 70mm
- Prior abdominal radiotherapy
- Evidence of metastatic disease on baseline radiologic investigations
- History of another malignancy within 2 years prior to randomisation, except adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial transitional cell carcinoma of the bladder, or any Stage 1 endometrial carcinoma. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 2 years after definitive primary treatment
- Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
- Neuroendocrine pancreatic carcinoma
- Life expectancy of less than 3 months
- Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must use a reliable means of contraception
- Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050, Australia
St George Hospital
Kogarah, New South Wales, 2217, Australia
Prince of Wales Hospital
Randwick, New South Wales, 2031, Australia
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Calvary Mater Newcastle
Waratah, New South Wales, 2298, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
ICON Cancer Centre, Gold Coast University Hospital
Southport, Queensland, 4215, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000, Australia
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Andrew Oar
ICON Gold Coast University Hospital, Southport, Queensland, AUS
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 4, 2019
First Posted
September 13, 2019
Study Start
October 1, 2019
Primary Completion
May 1, 2023
Study Completion
August 30, 2023
Last Updated
October 22, 2021
Record last verified: 2021-10
Data Sharing
- IPD Sharing
- Will not share
The study will be conducted in accordance with applicable Privacy Acts and Regulations. All data generated in this study will remain confidential. All information will be stored securely at the NHMRC CTC, University of Sydney and will only be available to people directly involved with the study. Personal data identifying trial participants will be held securely at the NHMRC CTC for the purpose of follow up if the patient is unable to/wishes to discontinue clinic based follow-up.