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

• ClinicalTrials.gov Identifier: NCT03207724
• Recruitment Status: Completed
• First Posted: July 5, 2017
• Last Update Posted: December 30, 2020
• Sponsor: Andrew Hendifar, MD
• Collaborators: Ipsen; Janssen Research & Development, LLC
• Information provided by (Responsible Party): Andrew Hendifar, MD, Cedars-Sinai Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer; Cachexia; Weight Loss	Drug: Xilonix plus Onivyde and 5FU	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study of Onivyde and 5-FU in Combination With Xilonix for Advanced Pancreatic Cancer With Cachexia
• Actual Study Start Date: October 16, 2017
• Actual Primary Completion Date: November 21, 2019
• Actual Study Completion Date: October 27, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Xilonix plus Onivyde and 5FU; interleukin-1-alpha antagonist (Xilonix) in addition to standard chemotherapy of onivyde and 5-fluorouracil/folinic acid (leucovorin)	Drug: Xilonix plus Onivyde and 5FU; Xilonix by IV; Other Name: interleukin-1-alpha antagonist

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

Sponsors and Collaborators

Andrew Hendifar, MD

Ipsen

Janssen Research & Development, LLC

Investigators

• Principal Investigator: Andrew Hendifar, MD; Cedars-Sinai Medical Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Erratum In: Sci Rep. 2022 Nov 4;12(1):18731.

• Responsible Party: Andrew Hendifar, MD, Assistant Professor of Medicine, Cedars-Sinai Medical Center
• ClinicalTrials.gov Identifier: NCT03207724
• Other Study ID Numbers: IIT2016-07-Hendifar-OnFX
• First Posted: July 5, 2017
• Last Update Posted: December 30, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Andrew Hendifar, MD, Cedars-Sinai Medical Center:

advanced pancreatic cancer; locally advanced pancreatic cancer; recurrent diagnosis; new diagnosis; adenocarcinoma

Additional relevant MeSH terms:

Pancreatic Neoplasms; Wasting Syndrome; Weight Loss; Cachexia; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Body Weight Changes; Body Weight; Emaciation; Metabolic Diseases; Nutrition Disorders