None listed
Conditions
Brief summary
The NEO-IMPACT study will assess the safety of combining standard chemotherapy (modified FOLFIRINOX) with immunotherapy (durvalumab) in patients with early stage pancreatic adenocarcinoma who are considered suitable for surgery. Who is it for? You may be eligible for this study if you are an adult aged 18 or older, you have been diagnosed with pancreatic cancer that is suitable for surgery (resectable or borderline resectable) and your kidneys, liver and bone marrow are considered healthy enough for you to take both chemotherapy and an immunotherapy drug. Study details All participants who choose to enrol in this study will undergo 6 treatment cycles every 2 weeks (for a total of 12 weeks) of combined immuno-chemotherapy (durvalumab with modified FOLFIRINOX). The chemotherapy (modified FOLFIRINOX) will be administered as a day patient in hospital. It is given via an intravenous (into a vein) infusion on day 1 of each cycle. One of the chemotherapy drugs (5-FU) will be given as a continuous infusion over 46 hours via a portable pump therefore you will return to the hospital on day 3 to have this pump disconnected , The immunotherapy drug (durvalumab) will be given via an intravenous infusion on day 1 of each second cycle i.e. cycles 1, 3 and 5. At the end of the 6 treatment cycles, participants will be assessed for their suitability for surgery. After surgery all participants will then undergo an additional 6 treatment cycles of chemotherapy alone (modified FOLFIRINOX). All participants will be monitored for 12 months after their surgery, This will include a medical review, blood tests and imaging with a CT scan every 3 months. It is hoped this research will determine if adding immunotherapy to standard chemotherapy affects how well the treatment is tolerated, and whether it will affect how much of the planned treatment can be completed (due to potential side effects). If the combined treatments are shown to be safe, they may be prescribed to future pancreatic cancer patients.
Interventions
Combination of modified FOLFIRINOX (mFOLFIRINOX) with durvalumab (MEDI4736) in patients with resectable or borderline resectable pancreatic adenocarcinoma in the neo-adjuvant setting;
Prior to surgery, eligible patients will receive 6 cycles of mFOLFIRINOX every 2 weeks given as follows:
- Oxaliplatin 85mg/m2 intravenously on day 1
- Irinotecan 150mg/m2 intravenously on day 1
- Calcium folinate (leucovorin) 50mgas an intravenous bolus
- Fluorouracil 2400mg/m2 by continuous infusion via pump over
Combination of modified FOLFIRINOX (mFOLFIRINOX) with durvalumab (MEDI4736) in patients with resectable or borderline resectable pancreatic adenocarcinoma in the neo-adjuvant setting; Prior to surgery, eligible patients will receive 6 cycles of mFOLFIRINOX every 2 weeks given as follows: - Oxaliplatin 85mg/m2 intravenously on day 1 - Irinotecan 150mg/m2 intravenously on day 1 - Calcium folinate (leucovorin) 50mgas an intravenous bolus - Fluorouracil 2400mg/m2 by continuous infusion via pump over 46 hours starting on day 1 - Pegylated G-CSF 6mg by subcutaneous injection to be given on day 3 of each cycle. Patients will also receive 3 cycles of durvalumab (MEDI4736) every 4 weeks given as follows: - Durvalumab 1500mg intravenously on day 1, with cycle 1, day 1 durvalumab treatment coinciding with cycle 1, day 1 of mFOLFIRINOX (ie. repeated on day 1 of cycle 3 and cycle 5 of mFOLFIRINOX. After completion of neoadjuvant therapy, all patients will be reviewed at the local multidisciplinary meeting (MDM) to determine resectability of the primary tumour. Curative surgery should be planned to take place within 6-8 weeks following the final dose of neoadjuvant therapy, with standard preoperative assessments to determine suitability. Adjuvant (post-surgery) chemotherapy will start within 8-12 weeks of surgery and consist of 6 cycles of mFOLFIRINOX administered in the say way as that administered prior to surgery. There will be no adjuvant durvalumab.
Sponsors
Australasian Gastro-Intestinal Trials Group (AGITG)
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Pancreatic adenocarcinoma proven by histology or cytology that is resectable or borderline resectable. Good performance status (ECOG 0 - 1) Adequate kidney, liver and bone marrow function to be able to undergo immuno-chemotherapy Body weight above 30kg Life expectancy of at least 12 weeks Tumour lesion on CT or MRI scan that is measurable
Exclusion criteria
Locally advanced or metastatic pancreatic adenocarcinoma. Neuroendocrine pancreatic carcinoma. Prior treatment for pancreatic cancer (including another clinical trial). Complete or intermediate dihydropyrimidine dehydrogenase deficiency (DPYD deficiency) Major surgical procedure within 28 days prior to the first dose of immuno-chemotherapy. History of allogenic organ transplantation. Active or prior autoimmune or inflammatory disorders such as inflammatory bowel disease (eg. colitis, Crohn's disease), systemic lupus erythematosus, Sarcoidosis syndrome, Wegener syndrome (granulomatosis with polyangitis, Graves disease, rheumatoid arthritis, hypophysitis, uveitis). Uncontrolled intercurrent illness (such as ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrheoa, psychiatric illness/social situations that would limit compliance with study requirements). History of another primary malignancy (except malignancy treated with curative intent and with no know active disease for more than 5 years, or adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease or adequately treated carcinoma insitu without evidence of disease or history of leptomeningeal carcinomatosis or history of active primary immunodeficiency). Active infection with TB, hepatitis B or hepatitis C. HIV positive. Current or prior use of immunosuppressive medication within 14 days before the first dose of immunotherapy. Receipt of live attenuated vaccine within 30 days prior to the first dose of immuno-chemotherapy. Patients who are pregnant or breast-feeding. Patients or partners of patients, who are of reproductive potential and are unwilling to use effective birth control from screening to 90 days after the last dose of immunotherapy. Known allergy or hypersensitivity to any of the drugs (immuno-chemotherapy) used or their excipients.
Outcome results
None listed