Telotristat Ethyl for the Treatment of Carcinoid Heart Disease in Patients With Metastatic Neuroendocrine Tumor

NCT04810091 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: 2019-1205NCI-2021-00852
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

Brief Summary

This phase III trial compares the effect of telotristat ethyl and the current standard of care somatostatin analog therapy or somatostatin analog therapy alone in treating patients with neuroendocrine tumor that has spread to other places in the body (metastatic). Telotristat ethyl and somatostatin analog therapy may help to control carcinoid syndrome and carcinoid heart disease.

Conditions

Locally Advanced Neuroendocrine Neoplasm; Metastatic Neuroendocrine Neoplasm

Outcome Measures

Primary Outcomes (1)

• Percent Change in NTproBNP at 6 Months Visit From Baseline

  Percent change in N-terminal pro B-type natriuretic peptide (NT-proBNP) from baseline to 6 months defined as (NTproBNP at 6 month - NTproBNP at baseline)/(NTproBNP at baseline)\*100

  Baseline and at 6 months

Secondary Outcomes (21)

• Change in 6MWT at 3 Month Visit

  Baseline and 3 month follow-up

• Change in 6MWT at 6 Month Visit

  Baseline and 6 month follow-up

• Change in CVHD % Score From Baseline to 3 Month Visit

  Baseline and 3 month follow-up

• Change in CVHD Score From Baseline to 6 Month Visit

  Baseline and 6 month follow-up

• Percentage of Participants With Significant Change in Strain-RV From Baseline at 3 Months

  Baseline and 3 month follow-up

Study Arms (2)

Arm A (telotristat ethyl, SSA)

EXPERIMENTAL

Patients receive telotristat ethyl PO TID and SSA for 6 months in the absence of disease progression or unacceptable toxicity.

Other: Questionnaire Administration; Drug: Telotristat Ethyl

Arm B (placebo, SSA)

ACTIVE COMPARATOR

Patients receive placebo PO TID and SSA for 6 months in the absence of disease progression or unacceptable toxicity.

Drug: Placebo Administration; Other: Questionnaire Administration

Interventions

Placebo Administration DRUG

Given PO

Arm B (placebo, SSA)

Telotristat Ethyl DRUG

Given PO

Arm A (telotristat ethyl, SSA)

Questionnaire Administration OTHER

Ancillary studies

Arm A (telotristat ethyl, SSA); Arm B (placebo, SSA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who are \>= 18 years old will be eligible for the study
• Histopathologically-confirmed,metastatic neuroendocrine tumor and/or locally/regionally advanced neuroendocrine tumor
• Documented history of carcinoid syndrome based on clinical parameters
• Currently receiving stable-dose somatostatin analog (SSA) therapy defined as \>= 2 months
• Dose of long-acting release (LAR) or depot SSA therapy and on at least:
• Octreotide LAR at 30 mg every 4 weeks
• Lanreotide depot at 120 mg every 4 weeks
• Patients who cannot tolerate SSA therapy at a level indicated above will be allowed to enter at their highest tolerated dose
• Ability and willingness to provide written informed consent
• Patients of childbearing potential must agree to use an adequate method of contraception during the study and for 30 days after the last dose of telotristat ethyl
• Childbearing potential is defined as those who have not undergone surgical sterilization (eg. documented hysterectomy, tubal ligation, or bilateral salpingo-oophorectomy) or those who are not considered postmenopausal (defined as 12 months of spontaneous amenorrhea).
• Adequate methods of contraception, defined as having a failure rate of \< 1% per year, for patients or their partner include the following: condom with spermicidal gel, diaphragm with spermicidal gel, intrauterine device, surgical sterilization, vasectomy, oral contraceptive pill, depo-progesterone injections, progesterone implant (ie, Implanon), patch (Ortho Evra), NuvaRing, and abstinence. If a patient is not sexually active but becomes active, he or his partner should use medically accepted forms of contraception
• Eastern Cooperative Oncology Group (ECOG) 0-2

You may not qualify if:

• Previous exposure to telotristat ethyl (XERMELO) in the last 3 months
• History of active treatment for malignancy, other than neuroendocrine tumor (malignancies that in the opinion of the Investigator are considered cured, may participate)
• Treatment with any tumor directed therapy, including interferon, chemotherapy, mechanistic target of rapamycin (mTOR) inhibitors \< 4 weeks prior to screening, or hepatic embolization, radiotherapy, peptide receptor radionuclide therapy, and/or tumor debulking \< 12 weeks prior to screening
• History of short bowel syndrome or other known causes of diarrhea unrelated to carcinoid syndrome
• Clinically significant (as per primary investigators judgement) cardiac arrhythmia, bradycardia, tachycardia that would compromise patient safety or the outcome of the study
• Estimated glomerular filtration rate estimated glomerular filtration rate (eGFR) \< 30 ml/min
• Hepatic laboratory values of aspartate transaminase (AST) or alanine aminotransferase (ALT):
• \> 5 x upper limit of normal (ULN) if patient has documented history of hepatic metastases; or
• \> 2.5 x ULN if no liver metastases are present
• Pregnant or lactating patients
• Patients receiving everolimus due to poor response to SSA
• Life expectancy \< 6 months
• Any other clinically significant laboratory abnormality that would compromise patient safety or the outcome of the study as per primary investigators judgement
• Any clinically significant and/or uncontrolled cardiac-related abnormality that would compromise patient safety or the outcome of the study including as per primary investigators judgement, but not limited to:
• Arrhythmia causing hemodynamic compromise

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

telotristat ethyl

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Cezar A. Iliescu, MD
• Organization: M.D. Anderson Cancer Center

ciliescu@mdanderson.org

(713) 792-4728

Study Officials

• Cezar A Iliescu, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2021
• First Posted: March 22, 2021
• Study Start: May 18, 2021
• Primary Completion: August 31, 2025
• Study Completion (Estimated): August 3, 2026
• Last Updated: March 9, 2026
• Results First Posted: February 5, 2026

Record last verified: 2026-03

Locations

US (1)