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