Enterade in Carcinoid/Non-Carcinoid Syndrome Neuroendocrine Tumor Patients With Quality of Life Limiting Bowel Frequency

Study Overview
=================
Brief Summary
-----------------
This is an open-label phase II basket study evaluating the ability of enterade® to reduce bowel frequency in neuroendocrine tumor (NET) patients with carcinoid syndrome and non-carcinoid syndrome.

Detailed Description
-----------------
Primary Objective: - To assess the ability of enterade to reduce bowel movement frequency in NET patients with and without carcinoid syndrome. Secondary Objectives: To assess subject-reported health-related quality of life measures in subjects before and after compound administration. To characterize the side effect profile and tolerability of the compound as measured by the number of total 8-oz enterade® bottles consumed throughout the trial. To evaluate changes in serum electrolytes before and after administration of the compound. To assess differences in intravenous fluid requirement and/or hospitalizations for dehydration in patients between observation period and active enterade® period. To evaluate differences in utilization of standard-of-care anti-diarrheal medications in patients between observation period and enterade® period. To compare subjective bloating and flatulence in patients before and after administration of the compound. To evaluate changes in patient weight before and after administration of the compound. Exploratory Objectives: To assess changes in serum and stool inflammatory markers before and after the study compound. To evaluate changes in fecal lactoferrin before and after study compound administration.

Official Title
-----------------
Proprietary Amino Acid-Based Medical Food (Enterade) in Carcinoid Syndrome and Non-Carcinoid Syndrome Neuroendocrine Tumor Patients With Quality of Life Limiting Bowel Frequency

Conditions
-----------------
Neuroendocrine Tumor, Carcinoid Syndrome

Intervention / Treatment
-----------------
* Dietary Supplement: Enterade®
* Other: Functional Assessment of Chronic Illness Therapy for Patients with Diarrhea (version 4.0)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Carcinoid syndrome: Participants must have histopathologically confirmed neuroendocrine tumor with 4 or more bowel movements per day on standard anti-diarrheal regimen (which includes somatostatin analogs and/or Telotristat Ethyl). Additionally, a plasma 5-HIAA, or a urine 24-hour 5-HIAA or plasma secretory hormone levels (VIP, gastrin) above the upper limit of normal per reference lab. Patients may be grouped into this cohort based on a previous plasma 5-HIAA level though the final cohort determination will be made based upon the 5-HIAA level drawn during screening. Non-Carcinoid Syndrome: Participants who have histopathologically confirmed neuroendocrine tumor and have 4 or more bowel movements per day on standard anti-diarrheal regimen (which may or may not include somatostatin analogs), but do not have elevated results for one of the following: plasma 5-HIAA, or 24-hour urine 5-HIAA or other plasma secretory hormone levels (VIP, gastrin) above the upper limit of normal per reference lab. Patients may be grouped into this cohort based on a previous plasma 5-HIAA level though the final cohort determination will be made based upon the 5-HIAA level drawn during screening ECOG performance status ≤ 2 (Karnofsky ≥60%) Ability to tolerate thin liquids by mouth at the time of enrollment. Ability to understand and the willingness to sign a written informed consent document. Subject who are willing to take enterade® as instructed will be eligible. Exclusion Criteria: Known allergy to Stevia. Uncontrolled intercurrent illness including, but not limited to, ongoing or active Clostridium difficile infection or history of Clostridium difficile infection. Participants with a history of inflammatory bowel disease, irritable bowel syndrome, bariatric surgery and/or Celiac disease. Participants with psychiatric illness/social situations that would limit compliance with study requirements. Patients who have had enterade® within the past 3 months. Pregnant or breastfeeding women. The safety of enterade® has not been validated in this patient population.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enterade<br>Carcinoid Syndrome: Participants will drink a bottle of Enterade two time per day for 4 weeks. | Dietary Supplement: Enterade®<br>* Participants will drink an 8 ounce bottle of Enterade® twice a day for 4 weeks<br>Other: Functional Assessment of Chronic Illness Therapy for Patients with Diarrhea (version 4.0)<br>* Ancillary studies<br>* Other names: FACIT-D;|
| Experimental: Experimental<br>Non-Carcinoid Syndrome: Participants will drink a bottle of Enterade two time per day for 4 weeks. | Dietary Supplement: Enterade®<br>* Participants will drink an 8 ounce bottle of Enterade® twice a day for 4 weeks<br>Other: Functional Assessment of Chronic Illness Therapy for Patients with Diarrhea (version 4.0)<br>* Ancillary studies<br>* Other names: FACIT-D;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bowel movement frequency | Changes in number of average daily bowel movements from baseline | At 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health-Related Quality of Life: Functional Assessment of Chronic Illness Therapy for Patients with Diarrhea (FACIT-D) version 4.0 | The FACIT-D is a questionnaire composed of 5 categories (physical well-being, social/family well-being, emotional well-being, functional well-being and additional concerns). Each category has 6-11 questions which are scored on a 0 (not at all) to 4 (very much) scale. Groups of categories are scored differently. For example in the additional concerns, emotional well-being and physical well-being categories, a higher score reflects poorer quality of life. In the family well-being and functional well-being categories, a higher score indicates better outcomes. | At 8 weeks | 
| Tolerability of enterade®: number of enterade® drinks consumed | Measured by the total number of enterade® drinks consumed | At 8 weeks | 
| Incidents adverse events | NCI CTCAE version 5.0 | At 8 weeks | 
| Change in serum electrolytes (Sodium) | The electrolyte sodium will be assessed for each patient before and after enterade® (measured in mmol/L) | At 8 weeks | 
| Change in serum electrolytes (Potassium) | The electrolyte potassium will be assessed for each patient before and after enterade® (measured in mmol/L) | At 8 weeks | 
| Change in serum electrolytes (Chloride) | The electrolyte chloride will be assessed for each patient before and after enterade® (measured in mmol/L) | At 8 weeks | 
| Change in serum electrolytes (Magnesium) | The electrolyte magnesium will be assessed for each patient before and after enterade® (measured in mg/dL ) | At 8 weeks | 
| Change in serum electrolytes (Phosphorous) | The electrolyte phosphorous will be assessed for each patient before and after enterade® (measured in mg/dL ) | At 8 weeks | 
| Differences in intravenous fluid requirements | Measured by the number of incidence requiring intravenous fluid before and after taking enterade® | At 8 weeks | 
| Differences in use of standard-of-care anti-diarrhea medications | Measured by reported incidence of standard-of-care anti-diarrhea medications usage before and after taking enterade® | At 8 weeks | 
| Differences in bloating | Measured by reported incidence of bloating before and after taking enterade® | At 8 weeks | 
| Differences in flatulence | Measured by reported incidence of flatulence before and after taking enterade® | At 8 weeks | 
| Changes in weight | Measured by fluctuation in weight before and after taking enterade® | At 8 weeks |