Study of Onivyde and 5-FU in Combination With Xilonix for Pancreatic Cancer With Cachexia

This study will prospectively evaluate advanced pancreatic adenocarcinoma patients. The intervention will be interleukin-1-alpha antagonist (Xilonix) in addition to standard chemotherapy. The first aim is to assess the safety and identify the maximum tolerated dose of Onivyde with 5-fluorouracil/folinic acid in combination with the study agent, Xilonix. The study will also create a repository of serum, tissue, and fecal specimens to investigate novel biomarkers related to cachexia with pancreatic adenocarcinoma and interleukin-1-alpha blockade. Lastly, the study will assess for a correlation between cachexia, activity, and PROs on domains of quality of life.

Inclusion criteria

• Advanced or locally advanced pancreatic cancer patients (can include new or recurrent diagnosis) referred to SOCCI-CSMC for chemotherapy that has progressed through or intolerant to gemcitabine based chemotherapy
• Cachexia defined as greater than 5% unexplained weight loss within any 6 month period prior to screening visit OR as documented by the medical physician based on standard diagnosis of cachexia
• Age ≥ 18 years
• ECOG performance status 0-2 or Karnofsky PS >60%
• Patients must have normal organ and marrow function
• Ability to understand and the willingness to sign a written informed consent
• Negative pregnancy test for WOCBP
• WOCBP and men must agree to use of adequate contraception

Exclusion criteria

• Patients who are currently receiving any other investigational agents
• Patients who have received more than one chemotherapeutic regimen in metastatic setting
• Patients with CNS metastases
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with unresolved grade 3/4 adverse effects of prior therapy at time of enrollment
• Subjects with history of hypersensitivity to compounds of similar chemical or biologic composition to Xilonix or Onivyde
• Women who are pregnant or breastfeeding
• Dementia or altered mental status that would prohibit the understanding or rendering of informed consent
• Patients with known Dihydropyrimidine dehydrogenase deficiency (DPD deficiency)
• Patients known to be UGT1A1*28 allele homozygous
• Patients who have had a live vaccine within 3 months of enrollment