Pancreaze (Pancrelipase) for Patients With Pancreatic Adenocarcinoma With Cachexia and Exocrine Pancreatic Insufficiency (PANCAX-3)

Pancreatic-enzyme Replacement Therapy With Pancreaze (Pancrelipase) Delayed-release in Addition to Standard of Care for Borderline Resectable, Locally Advanced, and Advanced Pancreatic Adenocarcinoma Patients (PANCAX-3) With Cachexia and Exocrine Pancreatic Insufficiency

The objective of this study is to assess weight stability, functional changes, and quality of life when Pancreaze (pancrelipase) delayed-release 84,000-lipase units (capsules), for main meals, and 42,000-lipase units (capsules), for snacks, are added to standard of care in patients with exocrine pancreatic insufficiency due to pancreatic adenocarcinoma. This will be the first prospective study of this particular formulation in addition to standard of care in advanced pancreatic cancer patients. We will treat 40 consecutive patients with borderline resectable, locally advanced and advanced pancreatic cancer patients who present with weight loss and exocrine pancreatic insufficiency with this advanced formulation of Pancreaze.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Pancrelipase

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andrew Hendifar, MD, MPH; Phone Number: 310-423-2217; Email: Andrew.Hendifar@cshs.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Sub-Investigator: Gillian Gresham, PhD
      • Sub-Investigator: Jun Gong, MD
      • Principal Investigator: Andrew Hendifar, MD
      • Contact: Abrahm Levi; Phone Number: 310-248-8084; Email: abrahm.levi@cshs.org
      • Sub-Investigator: Arsen Osipov, MD
      • Sub-Investigator: Meghan Laszlo, RD
      • Sub-Investigator: Kamya Sankar, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Borderline resectable, locally advanced, and advanced pancreatic cancer patients (can include new or recurrent diagnosis) referred to SOCCI-CSMC
2. Age ≥ 18 years.
3. ECOG performance status 0-1 or Karnofsky PS >60%
4. Clinical diagnosis of exocrine pancreatic insufficiency
5. Cachexia defined as at least 5% weight loss in the presence of chronic illness, within any 6-month period prior to screening OR as documented by the medical physician based on standard diagnosis of cachexia
6. Life expectancy of greater than 3 months, in the opinion of the investigator.

7. Patients must have normal organ and marrow function as defined below:

   • Absolute Neutrophil Count (ANC) ≥ 500/mcL
   • Platelets ≥ 50,000/mcL
   • Total bilirubin ≤ 5X upper limit of normal (ULN)
   • AST(SGOT)/ALT(SGPT) ≤ 5 X ULN
   • Creatinine OR creatinine clearance ≤ 3 times the upper limit of normal OR ≥ 30 mL/min/1.73 m² for patients with creatinine levels above normal.
   • Note: Patients with biliary stents are eligible provided that all other inclusion criteria are met.
8. Woman of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of signing the informed consent form, for the duration of study participation, and for at least 30 days after discontinuing from study treatment.
9. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. 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.
2. Women who are pregnant or are breastfeeding
3. Dementia or altered mental status that would prohibit the understanding or rendering of informed consent
4. Unable to swallow intact capsules
5. Fibrosing colonopathy: Patients with history of fibrosing colonopathy have been reported to experience advancement to colonic strictures with doses of lipase>6000 units/kg/meal over prolonged periods of time.
6. History of chronic illness associated with malabsorption or nutrient deficiency including but not limited to chronic pancreatitis, cystic fibrosis, celiac disease, Crohn's disease, pernicious anemia and/or prior intestinal resection.
7. Coexistent other primary malignancy
8. Pregnancy, breastfeeding, or of childbearing potential and not willing to use methods of birth control during the study
9. Active drug abuse or intoxication with any substance including alcohol (blood alcohol content >0.08%, legal driving limit)
10. Known allergy to any of the active ingredients in pancreatic enzyme supplementation
11. Concurrent use of pancreatic enzyme supplementation or over the counter supplements which contain lipase, protease, and amylase as active ingredients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard of care treatment with Pancreaze (pancrelipase); Pancrelipase capsules; 84,000 IU lipase units per main meal and 42,000 IU lipase units per snack; for 24 weeks	Drug: Pancrelipase; Pancrelipase delayed-release capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of completing pancreatic enzyme replacement therapy during the first 8 weeks of the study: daily compliance diary	Adherence to therapy of at least 50% of the needed total lipase units, recorded using a daily compliance diary.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in weight from baseline through the end-of-study visit		6 months
Mean change in calories consumed from baseline through the end-of-study visit	As measured by Automated Self-Administered 24-Hour (ASA24) Dietary Assessment Tool. The ASA24 is a system to collect 24-hour food recalls and provide complete nutrient analysis of the foods and beverages consumed during the collection timeframe. The tool is used in this study to measure total calories consumed.	6 months
Mean change in stool frequency from baseline through Cycle 3 Day 1	As measured by patient reported number of bowel movements in the past 24 hours. In this study, higher numbers represent more severe symptoms; a reduction in number of bowel movements in the past 24 hours represents improvement in symptoms.	8 weeks
Mean change in stool consistency from baseline through Cycle 3 Day 1	As measured by patient reported stool consistency using the Bristol Stool Chart.The Bristol Stool Chart is a diagnostic scale to classify stool into 7 different groups, ranging from Type 1-7 (indicating solid to liquid consistency or time spent longest in the bowel to least time in the bowel). A normal stool should be either Type 3 or Type 4 (middle of the scale). Worsening of stool consistency is denoted by classifications located closer to the extreme ends of the scale (Type 1 or Type 7).	8 weeks
Mean change in serum levels of fat-soluble vitamins from baseline		6 months
Change in microbiome from baseline	Microbiome analysis of stool samples	8 weeks
Mean change in daily activity (steps taken) from baseline	As measured by continuous daily wearable activity monitor	6 months
Mean change in daily activity (stairs climbed) from baseline	As measured by continuous daily wearable activity monitor	6 months
Mean change in sleep duration from baseline	As measured by continuous daily wearable activity monitor	6 months
Mean change in sleep disturbances from baseline	As measured by continuous daily wearable activity monitor	6 months
Mean change in average heart rate from baseline	As measured by continuous daily wearable activity monitor	6 months
Mean change in peak heart rate from baseline	As measured by continuous daily wearable activity monitor	6 months
Mean change in daily active minutes from baseline	As measured by continuous daily wearable activity monitor	6 months

Collaborators and Investigators

• Sponsor: Andrew Hendifar, MD
• Collaborators: VIVUS LLC
• Investigators: Principal Investigator: Andrew Hendifar, MD, MPH, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2020
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: September 19, 2019
• First Submitted That Met QC Criteria: September 20, 2019
• First Posted (Actual): September 23, 2019

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 5, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Body Weight; Body Weight Changes; Pancreatic Diseases; Weight Loss; Thinness; Adenocarcinoma; Cachexia; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Pancrelipase; Pancreatin
• Other Study ID Numbers: IIT2018-29-HENDIFAR-PNCX3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No