NEO-adjuvant Chemo-immunotherapy in Pancreatic Cancer

NCT06094140 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NEO-IMPACT
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Pancreatic Cancer

Keywords

Resectable; Border-line; Pancreas

Outcome Measures

Primary Outcomes (1)

• The proportion of patients receiving at least 80% of planned neoadjuvant treatment.

  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).

  At completion of neo-adjuvant treatment (at 3 months post enrollment)

Secondary Outcomes (5)

• The proportion of patients missing surgery due to significant treatment related adverse events.

  Every 2 weeks during neo-adjuvant treatment, at the completion of treatment (at 3 months post enrolment) and 30 to 42 days after the last dose of immunotherapy.

• Treatment tolerability (Rates of adverse events as per CTCAE v5.0).

  Through study completion, an average of 1 year

• R0 resection rate.

  Through study completion, an average of 1 year

• Pathological complete response rate.

  Through study completion, an average of 1 year

• Objective response rate.

  Through study completion, an average of 1 year

Other Outcomes (2)

• To monitor the change in microbiome during neoadjuvant therapy.

  At baseline, at end of neoadjuvant treatment (within 2 weeks of last dose) and post-operatively (14-42 days post surgery, prior to commencement of adjuvant treatment)

• Analysis of tumour tissue (baseline and surgical resection) for molecular changes and gene expression profile.

  Through study completion, an average of 1 year

Study Arms (1)

Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.

EXPERIMENTAL

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

Drug: Durvalumab; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Calcium folinate (leucovorin); Drug: Fluorouracil; Drug: Pegylated G-CSF

Interventions

Durvalumab DRUG

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.

Also known as: Imfinzi

Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.

Oxaliplatin DRUG

85mg/m2 intravenously on day 1

Also known as: Eloxatin

Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.

Irinotecan DRUG

150mg/m2 intravenously on day 1

Also known as: Camptosar, Campto

Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.

Calcium folinate (leucovorin) DRUG

50mg as an intravenous bolus

Also known as: Folinic acid

Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.

Fluorouracil DRUG

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

Also known as: Adrucil

Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.

Pegylated G-CSF DRUG

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

Also known as: Neulasta

Single arm study, mFOLFIRINOX and durvalumab, neoadjuvant resectable pancreatic cancer.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults, aged 18 years and older, with cytologically or histologically proven resectable or borderline resectable pancreatic adenocarcinoma as per Australasian Gastro-Intestinal Trials Group (AGITG) consensus guidelines. Those in whom cytology is suspicious for pancreatic adenocarcinoma but not diagnostic may be allowed on study following discussion with the study chair (or their representative).
• ECOG 0-1
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1.5 × 109 /L
• Platelet count ≥100× 109/L
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). \[This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.\]
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional ULN unless;
• o There has been recent biliary drainage in the past 30 days, in which case it must be ≤5 x ULN
• Measured creatinine clearance (CL) \>50 mL/min or Calculated creatinine CL \>50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) / 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 / 72 x serum creatinine (mg/dL)
• Study treatment both planned and able to start within 14 days of registration.
• Body weight \>30 kg.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Must have a life expectancy of at least 12 weeks.
• Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to first study treatment.

You may not qualify if:

• Locally advanced or metastatic pancreatic adenocarcinoma.
• Neuroendocrine pancreatic carcinoma.
• Prior treatment for pancreatic cancer including chemotherapy, checkpoint inhibitor or investigational treatments, the exception of a maximum of 1 cycle of neoadjuvant intent mFOLFIRINOX.
• Participation in another clinical study with an investigational product during the last 30 days.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or enrolment occurs during the follow-up period.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia.
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
• Any chronic skin condition that does not require systemic therapy.
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
• Patients with coeliac disease controlled by diet alone.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, active infection requiring systemic therapy within 14 days before the first dose of study drug, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.

Sponsors & Collaborators

• Australasian Gastro-Intestinal Trials Group: lead
• The University of New South Wales: collaborator
• Walter and Eliza Hall Institute of Medical Research: collaborator

Study Sites (3)

GenesisCare North Shore

Sydney, New South Wales, 2065, Australia

Location

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

Location

Warringal Private Hospital

Melbourne, Victoria, 3084, Australia

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

durvalumab; Oxaliplatin; Irinotecan; Leucovorin; Fluorouracil; pegfilgrastim

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Lorraine Chantrill, Professor

  AGITG

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2023
• First Posted: October 23, 2023
• Study Start: May 20, 2022
• Primary Completion: June 30, 2024
• Study Completion (Estimated): June 1, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)