Based on a central role of inflammation in pancreas cancer, the role of IL 1 in acute and chronic inflammation , the inhibitory effect of IL 1 alfa and beta by anakinra and preliminary experience with anakinra in combination with chemotherapy in metastasis (with FOLFIRINOX) and localized disease (with gemcitabine/abraxane/cisplatin), a phase 2 study with anakinra in combination with perioperative chemotherapy for patients with PDAC is being proposed.
This is an open-label, single-arm, prospective phase II study conducted by Baylor Scott and White Research Institute in Dallas. The study will enroll patients with pancreatic adenocarcinoma that are planned to receive pre-operative chemotherapy followed by surgical resection and post operative treatment. Local surgical/biopsy and pathology reports will constitute adequate documentation of histology/cytology for study inclusion. Patients will receive pre- and post-operative chemotherapy plus Anakinra. Specifically, the pre-operative chemotherapy regimen will be a combination of Nab-paclitaxel, gemcitabine and cisplatin, while post-operative chemotherapy will use 5-Fluorouracil, oxaliplatin, and irinotecan. Patients will also receive growth factor (Neupogen followed by Neulasta) for safety and to ensure that treatment is not delayed due to neutropenic effects of chemotherapy. Anakinra will be self-administered by the participants through out the treatment period. A treatment break of 2 days will be given prior to the surgery day.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Anakinra (100 mg) twice a day (BID), daily, will be self-administered subcutaneously starting on D1 of chemotherapy. Anakinra will be held 2 days prior to surgery. A dosing diary will be given to the patient for anakinra documentation.
Baylor University Medical Center, Charles A Sammons Cancer Center
Dallas, Texas, United States
RECRUITINGTo determine the percentage of patients that have a normalization of CA19-9 after pre-op treatment with the combination of nab-paclitaxel (abraxane), gemcitabine, cisplatin and anakinra.
Time frame: 24 months
To determine the effect of anakinra in combination with perioperative chemotherapy on overall survival (OS) of PDAC patients. A benchmark of 24 months OS will be used to determine how many patients meet or exceed this goal.
Time frame: 24 months
To determine the effect of anakinra in combination with perioperative chemotherapy on the median disease free survival (DFS). A benchmark of 12 months DFS will be used to determine how many patients meet or exceed this goal.
Time frame: 12 months
To determine the effect of anakinra in combination with perioperative chemotherapy on response rate
Time frame: 24 months
To determine the R0 resection rates (complete tumor removal with negative resection margins) obtained with anakinra + pre-operative chemotherapy.
Time frame: 24 months
To describe the effect of anakinra in combination with perioperative chemotherapy on the prevalence and severity of pain by monitoring patients' pain level using memorial pain assessment card (MPAC).
Time frame: 24 months
To determine the effect of anakinra in combination with perioperative chemotherapy on patients' health-related quality of life by monitoring patients using EORTC quality of life survey questionnaire (EORTC QLQ-C30).
Time frame: 24 months
To determine the effect of anakinra in combination with perioperative chemotherapy on the inflammasomes ( IL6, CRP, IL1α and IL1β) in blood and in the resected pathology specimens.
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Time frame: 24 months