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

Study Overview
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Brief Summary
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This study is being conducted to examine the safety of the investigational drug, Xilonix(™), in addition to standard doses of Onivyde® (nanoliposomal irinotecan) and 5- fluorouracil (5FU)/folinic acid (leucovorin) for pancreatic cancer patients with cachexia. Cachexia is a syndrome that includes involuntary weight loss and physical deterioration that can contribute to poor outcomes of cancer treatment. In other studies, Xilonix has increased lean body mass in advanced cancer patients. This increase could lead to improved weight maintenance and quality of life.

Detailed Description
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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.

Official Title
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A Phase I Study of Onivyde and 5-FU in Combination With Xilonix for Advanced Pancreatic Cancer With Cachexia

Conditions
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Pancreatic Cancer, Cachexia, Weight Loss

Intervention / Treatment
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* Drug: Xilonix plus Onivyde and 5FU


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xilonix plus Onivyde and 5FU<br>interleukin-1-alpha antagonist (Xilonix) in addition to standard chemotherapy of onivyde and 5-fluorouracil/folinic acid (leucovorin) | Drug: Xilonix plus Onivyde and 5FU<br>* Xilonix by IV<br>* Other names: interleukin-1-alpha antagonist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the determination of the Maximum Tolerated Dose (MTD) | Assess safety of novel combination | 28 days (first cycle) | 
| Maximum Tolerated Dose (MTD) of onivyde, 5-fluorouracil/folinic acid in combination with Xilonix | Assess MTD of Onivyde in combination with novel therapy | 28 days (first cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight stability | Mean change from baseline (kg) up to 6 months | 6 months | 
| Lean Body Mass | Mean change from baseline (kg) up to 6 months | 6 months | 
| Overall Survival | To measure overall survival up to 12 months from baseline | 12 months | 
| Progression Free Survival | To measure progression free survival up to 12 months from baseline | 12 months | 
| Mean change in global quality of life (QOL) score (EORTC Pan26) | Assessment based on patient-reported QOL up to 6 months from baseline | 6 months | 
| Mean change in global score of patient-reported response to therapy (FAACT questionnaire- Functional Assessment of Anorexia/Cachexia Therapy) | Assessment based on patient-reported outcomes up to 6 months from baseline | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent diagnosis, advanced pancreatic cancer, locally advanced pancreatic cancer, new diagnosis, adenocarcinoma