Clinical trial NCT03207724: Study of Onivyde and 5-FU in Combination With Xilonix for Pancreatic Cancer With Cachexia
Official title: A Phase I Study of Onivyde and 5-FU in Combination With Xilonix for Advanced Pancreatic Cancer With Cachexia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Cancer
Cachexia
Weight Loss
Keywords: advanced pancreatic cancer
locally advanced pancreatic cancer
recurrent diagnosis
new diagnosis
adenocarcinoma
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
Collaborators: name: Ipsen
name: Janssen Research & Development, LLC
First posted: 2017-07-05
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the determination of the Maximum Tolerated Dose (MTD)
timeFrame: 28 days (first cycle)
measure: Maximum Tolerated Dose (MTD) of onivyde, 5-fluorouracil/folinic acid in combination with Xilonix
timeFrame: 28 days (first cycle)
Secondary outcomes:
measure: Weight stability
timeFrame: 6 months
measure: Lean Body Mass
timeFrame: 6 months
measure: Overall Survival
timeFrame: 12 months
measure: Progression Free Survival
timeFrame: 12 months
measure: Mean change in global quality of life (QOL) score (EORTC Pan26)
timeFrame: 6 months
measure: Mean change in global score of patient-reported response to therapy (FAACT questionnaire- Functional Assessment of Anorexia/Cachexia Therapy)
timeFrame: 6 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Andrew Hendifar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gong J, Thomassian S, Kim S, Gresham G, Moshayedi N, Ye JY, Yang JC, Jacobs JP, Lo S, Nissen N, Gaddam S, Tighiouart M, Osipov A, Hendifar A. Phase I trial of Bermekimab with nanoliposomal irinotecan and 5-fluorouracil/folinic acid in advanced pancreatic ductal adenocarcinoma. Sci Rep. 2022 Sep 2;12(1):15013. doi: 10.1038/s41598-022-19401-3.