Clinical trial NCT04089150: MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease
Official title: MASTERPLAN: A Randomised Phase II Study of MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: stereotactic body radiotherapy
SBRT
chemotherapy
radiotherapy
surgery
Lead sponsor: Australasian Gastro-Intestinal Trials Group
Sponsor class: NETWORK
Collaborators: name: Trans Tasman Radiation Oncology Group
name: Australian Government Department of Health and Ageing
First posted: 2019-09-13
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Locoregional control (Locoregional Response Rate LRR)
timeFrame: Within 12 months of randomisation;
Secondary outcomes:
measure: Safety (NCI CTCAE v5.0)
timeFrame: 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
measure: Surgical morbidity/mortality (Clavien grading system)
timeFrame: At discharge post-surgery, 30 days and 90 days post surgery, up to 4 years
measure: Radiological response rates (RECIST v1.1)
timeFrame: 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.
measure: Progression Free Survival (PFS) (RECIST v1.1)
timeFrame: 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
measure: Pathological response rates (College of American Pathology Tumour Regression Grade TRG)
timeFrame: At SRBT/surgery compared to baseline;
measure: Surgical resection rates (Guidelines for the Evaluation of Resectability and Histology)
timeFrame: At surgery
measure: R0 resection rates (>1mm) (Synoptic PC histology reporting as outlined in Royal College of Pathologists of Australasia (RCPA)
timeFrame: At surgery
measure: Quality of Life (EORTC QLQ C30 and PAN26 QOL)
timeFrame: 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.
measure: Deterioration-Free Survival (DFS) (EORTC QLQ C30)
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: From the date of randomisation to date of death from any cause, or the date of last known alive; up to 4 years
Other outcomes:
measure: Exploratory biomarker analysis of blood
timeFrame: 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
measure: Exploratory biomarker analysis of tissue
timeFrame: 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.
measure: ePRO Acceptability
timeFrame: 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.
Locations:
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Southport
country: Australia
facility: ICON Cancer Centre, Gold Coast University Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
Study officials:
affiliation: ICON Gold Coast University Hospital, Southport, Queensland, AUS
name: Andrew Oar
role: STUDY_CHAIR
References: