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

Phase 1

Completed

• Conditions: Pancreatic Cancer; Cachexia; Weight Loss
• Interventions: Drug: Xilonix plus Onivyde and 5FU

• Registration Number: NCT03207724
• Lead Sponsor: Andrew Hendifar, MD

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-06-30
• Study First Submitted QC: 2017-06-30
• Study First Posted: 2017-07-05
• Study Start: 2017-10-16
• Primary Completion: 2019-11-21
• Study Completion: 2020-10-27
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-29
• Last Update Posted: 2020-12-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Xilonix plus Onivyde and 5FU	Xilonix plus Onivyde and 5FU	interleukin-1-alpha antagonist (Xilonix) in addition to standard chemotherapy of onivyde and 5-fluorouracil/folinic acid (leucovorin)

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States