MASTERPLAN

Protocol Title

A randomised phase II study of MFOLFIRINOX And Stereotactic Radiotherapy (SBRT) for Pancreatic Cancer With High Risk and Locally Advanced Disease

Aim

To determine if adding SBRT to mFOLFIRINOX (OR gemcitabine/nab-paclitaxel) for patients with high-risk or unresectable (also called locally advanced) pancreatic cancer improves cancer control rates in and around the pancreas. If after 120 patients, the cancer control rate (termed locoregional control) is considered superior with SBRT (compared to without), we would consider proceeding to a larger trial.

Background

The five year overall survival for patients with pancreatic cancer (PC) is 8%. Patients with PC have inferior survival to patients with breast, prostate, cervical, bladder, colorectal, stomach, oesophagus, lung, kidney, liver and brain cancer. PC has the fifth highest incidence of cancer related mortality and accounts for the death of more than 2,900 Australians annually. For the 80% of PC patients with non-metastatic PC who have high-risk, borderline resectable (BRPC) or locally advanced pancreas cancer (LAPC), the 5-year overall survival is abysmal, at 12%. This is despite having no demonstrable metastatic disease at diagnosis. Approximately half of all PC patients experience locoregional recurrence (LRR). Even with surgery, 40% of patients will experience a LRR in the first 12 months [5]. LRR is the most common site of treatment failure for patients with PC and this is a major contributor to the substantial morbidity and mortality of this cancer. Clinical trials exploring new treatment paradigms for PC including stereotactic body radiotherapy (SBRT), molecular targets and novel biomarkers are recommended within international consensus guidelines. SBRT is a significant dose escalation to standard external beam radiotherapy (EBRT) without an increase in toxicity. This is anticipated to increase tumour cell kill and reduce rates of LRR. Reduced LRR rates could increase the likelihood of R0 resection allowing the possibility of cure, reduce the debilitating symptoms associated with LRR and progression, and potentially improve overall survival by preventing or delaying development of metastases. LRR is associated with significant pain and suffering due to gastric outlet obstruction, duodenal erosion and coeliac plexus infiltration, and ultimately results in premature death.

Clinical Trial Design

A multicentre randomised phase II study comparing SBRT with modern chemotherapy to modern chemotherapy alone for high-risk operable, borderline resectable and locally advanced pancreas cancer (n=120).

PATIENTS RECRUITED

Click to access the table and view recruitment data on all AGITG open trials:

Open Trial Recruitment Table

Key Eligibility Criteria

Inclusion Criteria

1. Adults, aged between 18-75 years, with histologic confirmation of pancreatic adenocarcinoma
2. Any of the following:
   • T3 (tumour >4 cm)
   • Extrapancreatic extension
   • Node positive (Stage IIB)
   • Borderline resectable pancreatic cancer
   • Locally advanced pancreatic cancer
3. Measurable disease according to RECIST v1.1
4. ECOG performance status 0-1
5. Adequate renal and haematological function.
6. 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
7. Study treatment planned to start within 14 days of registration.
8. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments
9. Signed, written informed consent

Exclusion Criteria

1. Tumour size greater than 70mm
2. Duodenal infiltration seen on endoscopy
3. Prior abdominal radiotherapy
4. Evidence of metastatic disease on baseline radiologic investigations
5. 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
6. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
7. Neuroendocrine pancreatic carcinoma
8. Life expectancy of less than 3 months
9. 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 randomisation. Men must use a reliable means of contraception
10. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol

Contact Email

Principal Investigator

Dr Andrew Oar

A/Prof Andrew Kneebone

Detailed Information Available on

More detailed information available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) or ClinicalTrials.Gov