Pancreatic Adenocarcinoma
Conditions
Brief summary
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.
Interventions
DRUGPancrelipase
Pancrelipase delayed-release capsules
Sponsors
Andrew Hendifar, MD
VIVUS LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Borderline resectable, locally advanced, and advanced pancreatic cancer patients (can include new or recurrent diagnosis) referred to SOCCI-CSMC (Samuel Oschin Cancer Center - Cedars Sinai Medical Center) 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Completing Pancreatic Enzyme Replacement Therapy During the First 8 Weeks of the Study: Daily Compliance Diary | 8 weeks | Adherence to therapy of at least 50% of the needed total lipase units, recorded using a daily compliance diary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 6 months | 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. |
| Mean Change in Stool Frequency From Baseline Through Cycle 3 Day 1 | 8 weeks | 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. |
| Mean Change in Stool Consistency From Baseline Through Cycle 3 Day 1 | 8 weeks | 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). |
| Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin A | 6 months | — |
| Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin D | 6 months | — |
| Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin E | 6 months | — |
| Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin K | 6 months | — |
| Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin K PT | 6 months | — |
| Change in Microbiome From Baseline | 8 weeks | Microbiome analysis of stool samples |
| Mean Change in Daily Activity (Steps Taken) From Baseline | 6 months | As measured by continuous daily wearable activity monitor |
| Mean Change in Daily Activity (Stairs Climbed) From Baseline | 6 months | As measured by continuous daily wearable activity monitor |
| Mean Change in Sleep Disturbance From Baseline | 6 months | As measured by continuous daily wearable activity monitor |
| Mean Change in Duration of Sleep Disturbances From Baseline | 6 months | As measured by continuous daily wearable activity monitor. An absolute change in the percentage of time during nighttime sleep in which participants experienced sleep disturbance is being reported.An absolute change in percent is understood to be calculated as the value at the later time point minus the value at the earlier time point (e.g., value at 6 months minus value at baseline). |
| Mean Change in Average Heart Rate From Baseline | 6 months | As measured by continuous daily wearable activity monitor |
| Mean Change in Peak Heart Rate From Baseline | 6 months | As measured by continuous daily wearable activity monitor |
| Mean Change in Daily Active Minutes From Baseline | 6 months | As measured by continuous daily wearable activity monitor |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAndrew Hendifar, MD, MPH
Cedars-Sinai Medical Center
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
Pancrelipase: Pancrelipase delayed-release capsules | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Standard of Care Treatment With Pancreaze (Pancrelipase) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 21 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 70 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 21 / 30 |
| other Total, other adverse events | 7 / 30 |
| serious Total, serious adverse events | 12 / 30 |
Outcome results
Primary
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.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Feasibility of Completing Pancreatic Enzyme Replacement Therapy During the First 8 Weeks of the Study: Daily Compliance Diary | 29 Participants |
Secondary
Change in Microbiome From Baseline
Microbiome analysis of stool samples
Time frame: 8 weeks
Secondary
Mean Change in Average Heart Rate From Baseline
As measured by continuous daily wearable activity monitor
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Average Heart Rate From Baseline | 0.8 beats per minute | Standard Error 2.6 |
Secondary
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.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Calories Consumed From Baseline Through the End-of-study Visit | -169.2075 calories | Standard Deviation 969.6394 |
Secondary
Mean Change in Daily Active Minutes From Baseline
As measured by continuous daily wearable activity monitor
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Daily Active Minutes From Baseline | 3.0 minutes/day | Standard Error 6.7 |
Secondary
Mean Change in Daily Activity (Stairs Climbed) From Baseline
As measured by continuous daily wearable activity monitor
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Daily Activity (Stairs Climbed) From Baseline | 1332.6 stair steps/day | Standard Error 539.4 |
Secondary
Mean Change in Daily Activity (Steps Taken) From Baseline
As measured by continuous daily wearable activity monitor
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Daily Activity (Steps Taken) From Baseline | -0.3 steps/day | Standard Error 3.8 |
Secondary
Mean Change in Duration of Sleep Disturbances From Baseline
As measured by continuous daily wearable activity monitor. An absolute change in the percentage of time during nighttime sleep in which participants experienced sleep disturbance is being reported.An absolute change in percent is understood to be calculated as the value at the later time point minus the value at the earlier time point (e.g., value at 6 months minus value at baseline).
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Duration of Sleep Disturbances From Baseline | 4.43 % of nighttime sleep | Standard Error 1.3 |
Secondary
Mean Change in Peak Heart Rate From Baseline
As measured by continuous daily wearable activity monitor
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Peak Heart Rate From Baseline | 9.6 BPM | Standard Error 5.4 |
Secondary
Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin A
Time frame: 6 months
Population: Some patients were missing vitamin values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin A | -0.5 mcg/dL | Standard Deviation 14.70231 |
Secondary
Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin D
Time frame: 6 months
Population: Some patients were missing vitamin values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin D | -5.37619 ng/mL | Standard Deviation 12.44841 |
Secondary
Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin E
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin E | 0.495 mg/L | Standard Deviation 3.988863 |
Secondary
Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin K
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin K | -27.47059 pg/mL | Standard Deviation 676.6716 |
Secondary
Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin K PT
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Serum Levels of Fat-soluble Vitamins From Baseline - Vitamin K PT | -0.2190476 pg/mL | Standard Deviation 2.82889 |
Secondary
Mean Change in Sleep Disturbance From Baseline
As measured by continuous daily wearable activity monitor
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Sleep Disturbance From Baseline | 0.5 hours/night | Standard Error 0.83 |
Secondary
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).
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Stool Consistency From Baseline Through Cycle 3 Day 1 | -0.407407 units on Bristol Stool Form Scale | Standard Deviation 1.906654 |
Secondary
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.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Stool Frequency From Baseline Through Cycle 3 Day 1 | -0.96296 bowel movements/day | Standard Deviation 2.457038 |
Secondary
Mean Change in Weight From Baseline Through the End-of-study Visit
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard of Care Treatment With Pancreaze (Pancrelipase) | Mean Change in Weight From Baseline Through the End-of-study Visit | -2.1931 lbs | Standard Deviation 6.163831 |