Open Label Study to Analyze the Effect of Telotristat Ethyl on Weight Regulation/Gain

• ClinicalTrials.gov Identifier: NCT04034745
• Recruitment Status: Withdrawn
• First Posted: July 26, 2019
• Last Update Posted: December 30, 2020
• Sponsor: Andrew Hendifar, MD
• Collaborator: Lexicon Pharmaceuticals
• Information provided by (Responsible Party): Andrew Hendifar, MD, Cedars-Sinai Medical Center

Study Description

Brief Summary:

This single arm study will evaluate whether Xermelo (telotristat ethyl) associated weight gain is affects lean body mass, dietary intake, and physical and cognitive functioning among neuroendocrine tumor (NET) patients with a history of carcinoid syndrome.

Condition or disease	Intervention/treatment
Pancreatic Cancer; Neuroendocrine Tumors; Cachexia; Cancer	Drug: telotristat ethyl

Detailed Description:

The purpose of this study is to examine the mechanisms of weight gain associated with the drug telotristat ethyl (Xermelo) among patients with a neuroendocrine tumor (NET) with history of carcinoid syndrome. We want to know if taking Xermelo affects patients' lean body mass, quality of life, dietary intake, and physical and cognitive functioning during treatment. A better understanding of the mechanisms of weight gain from Xermelo may allow us to determine whether this drug may be beneficial for treating carcinoid syndrome, cachexia, or weight loss seen in other diseases.

Study Design

• Study Type: Observational
• Actual Enrollment: 0 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: IIT2018-26 -Hendifar-NETCx: A Descriptive, Multicenter, Single-arm, Open Label Study to Analyze the Effect of Telotristat Ethyl on Weight Regulation/Gain
• Estimated Study Start Date: October 2020
• Estimated Primary Completion Date: November 2022
• Estimated Study Completion Date: November 2023

Groups and Cohorts

Group/Cohort	Intervention/treatment
Standard of Care telotristat ethyl (Xermelo) Treatment; Treatment of telotristat ethyl (Xermelo) with DXA scans and bionutritional assessments (24-hour food recall and taste/smell alteration) conducted 3x during telotristat ethyl treatment.	Drug: telotristat ethyl; 250 mg tablets of Xermelo (telotristat ethyl) is administered orally 3x daily in combination with somatostatin analogs (SSAs) for approximately 84 days as per standard of care; Other Name: Xermelo

Outcome Measures

Primary Outcome Measures :

1. Mean change in lean body mass (measured using DXA Scan) from baseline and after 13 weeks of treatment. [ Time Frame: From baseline to 13 weeks after treatment ]

Secondary Outcome Measures :

1. Mean change in patient reported outcomes using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) from baseline up to 3 years post treatment. [ Time Frame: From baseline to 3 years post treatment ]
   The summary score (SS) is a mean of 13 QLQ-C30 subscale scores, ranging from 0 to 100, with a higher SS rating reflecting a better health status.
2. Mean change in patient reported outcomes using the Montreal Cognitive Assessment (MOCA) test from baseline up to 3 years post treatment. [ Time Frame: From baseline to 3 years post treatment ]
   MOCA scores range between 0 and 30, with higher scores indicating higher cognitive function.
3. Mean change in patient reported outcomes using a stool survey measured from baseline and after 13 weeks of treatment. [ Time Frame: From baseline to 13 weeks post-treatment. ]
   The stool survey is a non-validated descriptive measure of gastrointestinal symptoms by taking the mean score on a scale of 0 - 10, where 0 indicates no symptoms and higher scores denote a worsening of symptoms.
4. Mean change in calories consumed using a 24-hour food diary from baseline and after 13 weeks of treatment. [ Time Frame: From baseline to 13 weeks post-treatment ]
5. Mean change in daily activity levels (steps) as measured using a wrist-worn fitness tracker (e.g., Fitbit) from baseline and for the duration of the 13 weeks of treatment. [ Time Frame: From baseline to 13 weeks post-treatment ]
6. Mean change in daily activity levels [stairs (floors) climbed] as measured using a wrist-worn fitness tracker (e.g., Fitbit) from baseline and for the duration of the 13 weeks of treatment. [ Time Frame: From baseline to 13 weeks post-treatment ]
7. Mean change in daily activity levels (sleep duration) as measured using a wrist-worn fitness tracker (e.g., Fitbit) from baseline and for the duration of the 13 weeks of treatment. [ Time Frame: From baseline to 13 weeks post-treatment ]
8. Mean change in daily activity levels (heart rate) as measured using a wrist-worn fitness tracker (e.g., Fitbit) from baseline and for the duration of the 13 weeks of treatment. [ Time Frame: From baseline to 13 weeks post-treatment ]
9. Mean change in daily activity levels (active minutes) as measured using a wrist-worn fitness tracker (e.g., Fitbit) from baseline and for the duration of the 13 weeks of treatment. [ Time Frame: From baseline to 13 weeks post-treatment ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited from Cedars-Sinai Medical Center

Criteria

Inclusion Criteria:

• Age ≥ 18 years.
• Histopathologically confirmed diagnosis of a metastatic NET.
• Documented history of carcinoid syndrome.
• Currently receiving treatment with long-acting SSAs with a plan to initiate therapy with telotristat-ethyl as per standard of care.
• ECOG performance status 0-1 and/or Karnofsky >60%.
• Greater than or equal to 3 month life expectancy.
• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Patients experiencing more than 12 watery BMs per day associated with volume contraction, dehydration, or hypotension, or showing evidence of enteric infection.
• History of short bowel syndrome.
• Clinically important baseline elevation in liver function tests.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Malignant ascites requiring paracenteses.
• 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.
• Bowel obstruction, partial, or total.
• Pregnancy
• Patients with unresolved grade 3/4 adverse effects of prior therapy at time of enrollment, other than diarrhea

Contacts and Locations

Sponsors and Collaborators

Andrew Hendifar, MD

Lexicon Pharmaceuticals

Investigators

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

More Information

• Responsible Party: Andrew Hendifar, MD, Assistant Professor of Medicine, Cedars-Sinai Medical Center
• ClinicalTrials.gov Identifier: NCT04034745
• Other Study ID Numbers: IIT2018-26 -Hendifar-NETCx
• First Posted: July 26, 2019
• Last Update Posted: December 30, 2020
• Last Verified: December 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Neuroendocrine Tumors; Cachexia; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Emaciation; Weight Loss; Body Weight Changes; Body Weight