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Durvalumab

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Calcium, Dietary

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Folinic Acid

Folate

Vitamin B9

Histidine

All patients enrolled to this study will receive mFOLFIRINOX, delivered Q2W for 6 cycles and durvalumab delivered Q4W for 3 cycles in the neoadjuvant setting for resectable or borderline resectable pancreatic cancer patients. Patients will then undergo restaging, discussion at MDM and surgical resection where appropriate. Following resection, patients will commence 6 cycles of adjuvant mFOLFIRINOX alone (or gemcitabine-based chemotherapy if deemed by investigator as more appropriate).

Patients will be followed up on study for 12 months from surgery, or from completion of neoadjuvant

Durvalumab will be supplied by AstraZeneca as a 500 mg vial concentrate for solution for infusion. The solution contains 50 mg/mL durvalumab, 26 mM histidine/histidine-hydrochloride, 275 mM trehalose dihydrate, and 0.02% weight/volume (w/v) polysorbate 80; it has a pH of 6.0 and density of 1.054 g/mL. The label-claim volume is 10 mL.

Durvalumab is a sterile, clear to opalescent, colorless to slightly yellow solution, free from visible particles.

Investigational product vials are stored at 2°C to 8°C (36°F to 46°F) and must not be frozen. Investigational product must be kept in original packaging until use to prevent prolonged light exposure.

Calcium folinate (leucovorin)

2400mg/m2 by continuous infusion via pump over 46 hours starting on day 1

6mg by subcutaneous injection to be given on day 3 of each cycle.

Pegylated G-CSF

Laura Carolan

Julia Kuszewski

Kathryn Jenkins

Sarah Maloney

Carly Leighton

Lorraine Chantrill

Yuan Guo

Niall Tebbutt

Lorraine Chantrill, Professor

To determine the safety and tolerability of adding durvalumab to mFOLFIRINOX prior to surgery in patients with resectable or borderline resectable pancreatic adenocarcinoma.

Despite curative surgery, pancreatic cancer patients have five-year survival rates of 20%. Adjuvant chemotherapy has improved survival in resected pancreatic cancer patients but only 10-15% are suitable for surgery and 30% of the resected pancreatic cancer patients miss out on adjuvant chemotherapy due to postoperative complications.

Neoadjuvant chemotherapy has improved the resection rates in the patients with non-metastatic pancreatic cancer. There is a growing interest to combine chemotherapy with checkpoint inhibitors to improve disease control in the early stage of pancreas cancer. The investigators propose a pilot study to evaluate the feasibility and safety of combining modified FOLFIRINOX (mFOLFIRINOX) with durvalumab (MEDI4736) in patients with resectable or borderline resectable pancreatic adenocarcinoma.

NEO-adjuvant Chemo-immunotherapy in Pancreatic Cancer

NEO-adjuvant Chemo-Immunotherapy in Pancreatic Cancer

Exploratory Objective - Collection of stool samples, oral swabs and tumour tissue to analyse microbiome changes during therapy.

Exploratory Objective - Immunohistochemistry of immune markers and Fluorescent In-situ Hybridisation to detect tissue localisation of the microbes.

80% of planned neoadjuvant treatment is defined as at least 5 cycles of mFOLFIRINOX and at least 2 of 3 cycles durvalumab. Dose modified cycles count towards received treatment.

Justification: As a pilot study, this primary objective addresses feasibility. A phase II study assessing use of neoadjuvant FOLFIRINOX in borderline resectable pancreatic cancer patients has previously demonstrated an 80% rate of receipt of all planned neoadjuvant therapy (Murphy et al 2018).

Address efficacy and safety of patients missing surgery due to significant treatment related adverse events.

Address efficacy and safety of treatment tolerability

Address efficacy and safety of the R0 resection rate.

Address efficacy and safety of the pathological complete response rate.

Address efficacy and safety of the objective response rate.

The University of New South Wales

Walter and Eliza Hall Institute of Medical Research

Australasian Gastro-Intestinal Trials Group

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
NEO-adjuvant Chemo-immunotherapy in Pancreatic Cancer	NCT06094140	Pancreatic Canc...	Durvalumab Oxaliplatin Irinotecan Calcium folinat... Fluorouracil Pegylated G-CSF	18 Years -	Australasian Gastro-Intestinal Trials Group
NEO-adjuvant Chemo-immunotherapy in Pancreatic Cancer	NCT06094140	Pancreatic Canc...	Durvalumab Oxaliplatin Irinotecan Calcium folinat... Fluorouracil Pegylated G-CSF	18 Years -	Australasian Gastro-Intestinal Trials Group

Spots Global Cancer Trial Database for calcium folinate (leucovorin)