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To determine the safety and tolerability of adding durvalumab to mFOLFIRINOX prior to surgery in patients with resectable or borderline resectable pancreatic adenocarcinoma.
Full description
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.
Enrollment
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Inclusion criteria
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.
Signed, written informed consent.
Exclusion criteria
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:
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.
History of another primary malignancy except for:
History of leptomeningeal carcinomatosis.
History of active primary immunodeficiency.
Active infection including:
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab.
Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
Prior randomisation or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.
Primary purpose
Allocation
Interventional model
Masking
20 participants in 1 patient group
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Central trial contact
Julia Kuszewski; Laura Carolan
Data sourced from clinicaltrials.gov
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