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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.
Full description
PRIMARY OBJECTIVE:
I. To estimate the percent change in N-terminal pro B-type natriuretic peptide (NT-proBNP) at 6 month visit from baseline after initiation of study drug in each arm and to compare the percent change between the two study arms.
SECONDARY OBJECTIVES:
I. To evaluate the change in functional capacity from baseline at 3 and 6 month visits as assessed by a 6 minute walk test (6MWT) in each arm.
II. To evaluate changes in echocardiographic parameters (Carcinoid Valvular Heart Disease [CVHD] score, global longitudinal myocardial strain assessment of the left and right ventricle/tricuspid annular plane systolic excursion [TAPSE]) from baseline to 3 and 6 month visits in each arm.
III. To evaluate the change from baseline to 3 and 6 month visits in plasma 5-hydroxyindoleacetic acid (5-HIAA) levels in each arm.
IV. To evaluate the change from baseline to 3 and 6 month visits in high sensitivity troponin T in each arm.
V. To evaluate the change from baseline to 3 and 6 month visits in health related quality of life with using the MD Anderson Symptom Inventory (MDASI) in each arm.
VI. To evaluate compliance of medications.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive telotristat ethyl orally (PO) three times daily (TID) and somatostatin analog therapy (SSA) for 6 months in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive placebo PO TID and SSA for 6 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Enrollment
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Inclusion criteria
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:
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
Eastern Cooperative Oncology Group (ECOG) 0-2
Exclusion criteria
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):
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:
Current complaints of persistent constipation or history of chronic constipation, bowel obstruction or fecaloma within the past 6 months
Investigator assessment of known history and/or uncontrolled hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus (HIV)-1 or HIV-2
History of substance or alcohol abuse (Diagnostic and Statistical Manual of Mental Disorders 5th edition [DSM-V] Criteria for Substance-Related Disorders) within the past 2 years
History of galactose intolerance, deficiency of Lapp lactase, or glucose-galactose malabsorption
Receipt of any investigational agent or study treatment (other treatment nor approved by Food and Drug Administration [FDA] for carcinoid syndrome or carcinoid heart disease) within the past 30 days
Existence of any surgical or medical condition that, in the judgment of the Investigator, might compromise patient safety or the outcome of the study
Presence of any clinically significant findings (relative to the patient population) during review of medical history or upon PE that, in the investigator's opinion, would compromise patient safety or the outcome of the study (e.g., psychiatric illness/social situations that would limit compliance with study requirements)
Unable or unwilling to communicate or cooperate with the Investigator for any reason
Primary purpose
Allocation
Interventional model
Masking
79 participants in 2 patient groups
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Central trial contact
Cezar A. Iliescu, MD
Data sourced from clinicaltrials.gov
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