MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease

Pancreatic Cancer Clinical Trial

— MASTERPLAN  

Official title:

MASTERPLAN: A Randomised Phase II Study of MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04089150
• Other study ID #: CTC 0245/AGITG AG0118PS
• Status: Recruiting
• Phase: Phase 2
• Start date: October 1, 2019
• Est. completion date: August 30, 2023

Study information

• Verified date: October 2021
• Source: Australasian Gastro-Intestinal Trials Group
• Contact: NHMRC CTC
• Phone: +61 (0) 2 9562 5000
• Email: masterplan[@]ctc.usyd.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a prospective, multicentre randomised, phase II clinical trial to evaluate safety and activity of stereotactic body radiotherapy (SBRT) in addition to chemotherapy in patients with high-risk and borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). High risk defined as any patient with tumour >4cm, extrapancreatic extension or node positive disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: August 30, 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Adults, aged between 18-75 years, with histological confirmation of pancreatic adenocarcinoma
• Any of the following

1. T3 (tumour >4 cm)

2. Extrapancreatic extension

3. Node positive (stage IIB)

4. 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Radiation:
• Stereotactic Radiotherapy (SBRT)
40 Gray (Gy) in 5 fractions, 2-3 fractions per week over two weeks, 8 Gy per fraction

Drug:
• mFOLFIRINOX
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
• Gemcitabine + Nab-paclitaxel
Day 1, Day 8 and Day 15 gemcitabine 1000mg/m2 + nab-paclitaxel 125mg/m2 28-day cycle, 3 cycles
• Gemcitabine + Capecitabine
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

Procedure:
• Pancreatoduodenectomy (Whipple procedure)
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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	St George Hospital	Kogarah	New South Wales
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	ICON Cancer Centre, Gold Coast University Hospital	Southport	Queensland
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland

Sponsors (3)

Lead Sponsor	Collaborator
Australasian Gastro-Intestinal Trials Group	Australian Government Department of Health and Ageing, Trans Tasman Radiation Oncology Group

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory biomarker analysis of blood	The list of blood biomarkers and their measurement will be updated when confirmed.	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
Other	Exploratory biomarker analysis of tissue	The list of tissue biomarkers and their measurement will be updated when confirmed.	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.
Other	ePRO Acceptability	Proportion of patients who are willing to use electronic device vs. paper format, Analysis of demographic data and assessing data quality between the group	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.
Primary	Locoregional control (Locoregional Response Rate LRR)	To determine if the addition of SBRT to chemotherapy improves locoregional control;	Within 12 months of randomisation;
Secondary	Safety (NCI CTCAE v5.0)	Compare acute and late side effects from chemotherapy +/- SBRT	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
Secondary	Surgical morbidity/mortality (Clavien grading system)	Length of stay, death within 30 days, frequency and severity of adverse events. Hospital admission during surgery will be calculated from day of surgery to date of discharge from acute care hospitalisation. The length of stay in acute hospital care will include intensive care admissions.	At discharge post-surgery, 30 days and 90 days post surgery, up to 4 years
Secondary	Radiological response rates (RECIST v1.1)	Compare radiologic response rates for chemotherapy +/- SBRT	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.
Secondary	Progression Free Survival (PFS) (RECIST v1.1)	Compare 12-month progression free survival	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
Secondary	Pathological response rates (College of American Pathology Tumour Regression Grade TRG)	Compare pathologic response rates of chemotherapy +/- SBRT	At SRBT/surgery compared to baseline;
Secondary	Surgical resection rates (Guidelines for the Evaluation of Resectability and Histology)	Compare rates of surgical resection	At surgery
Secondary	R0 resection rates (>1mm) (Synoptic PC histology reporting as outlined in Royal College of Pathologists of Australasia (RCPA)	Compare R0 resection rates (>1 mm)	At surgery
Secondary	Quality of Life (EORTC QLQ C30 and PAN26 QOL)	To assess the impact of the regimens on quality of life of patients	Baseline, Day 1 of each cycle of chemotherapy, prior to SBRT, post initial chemotherapy +/- SBRT, prior to surgery, 30 days post end of treatment, at months 3, 6,9 and 12 post randomisation 6 monthly in years 2, 3 and 4.
Secondary	Deterioration-Free Survival (DFS) (EORTC QLQ C30)	To assess overall net clinical benefit of treatment	The time until the first of the following events: a 10-point deterioration in health status from baseline, disease progression, death, or treatment discontinuation;up to 4 years
Secondary	Overall Survival (OS)	OS is defined as the interval from the date of randomisation to date of death from any cause, or the date of last known alive. Participants will be censored at the date of commencement of the subsequent anti-cancer therapy.	From the date of randomisation to date of death from any cause, or the date of last known alive; up to 4 years