NCT04810091进行中（未招募）3 期
TELEHEART: Telotristat Ethyl in a Heart Biomarker Study
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 79
- 试验地点
- 1
- 主要终点
- Percent Change in NTproBNP at 6 Months Visit From Baseline
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •Symptomatic severe valvular disease
- •Symptomatic congestive heart failure classified by New York Heart Association (NYHA) class IV
- •Evidence of ischemia on electrocardiography (ECG) with chest pain
- •Unstable angina pectoris
- •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
研究组 & 干预措施
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.
干预措施: Questionnaire Administration (Other)
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.
干预措施: Telotristat Ethyl (Drug)
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.
干预措施: Placebo Administration (Drug)
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.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Percent Change in NTproBNP at 6 Months Visit From Baseline
时间窗: Baseline and at 6 months
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
次要结局
- 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)
- Percentage of Participants With Significant Change in Strain-RV From Baseline at 6 Months(Baseline and 6 month follow-up)
- Percentage of Participants With Significant Change in Strain-LV From Baseline at 3 Months(Baseline and 3 month follow-up)
- Percentage of Participants With Significant Change in Strain-LV From Baseline at 6 Months(Baseline and 6 month follow-up)
- Percentage of Participants With Normal TAPSE at 3 Months(3 month follow-up)
- Percentage of Participants With Normal TAPSE at 6 Months(6 month follow-up)
- Change in 5HIAA From Baseline to 3 Months(Baseline and 3 month follow-up)
- Change in 5HIAA From Baseline to 6 Months(Baseline and 6 month follow-up)
- Change in Troponin From Baseline to 3 Months(Baseline and 3 months follow-up)
- Change in Troponin From Baseline to 6 Months(Baseline and 6 months follow-up)
- Change in MDASI Mean Core Symptom Score From Baseline to 3 Months(Baseline and 3 months follow-up)
- Change in Core Symptom Score From Baseline to 6 Months(Baseline and 6 months follow-up)
- Change in MDASI Mean Total Symptom Score From Baseline to 3 Months(Baseline and 3 months follow-up)
- Change in MDASI Mean Total Symptom Score From Baseline to 6 Months(Baseline and 6 months follow-up)
- Change in MDASI Mean Interference Score From Baseline to 3 Months(Baseline and 3 months follow-up)
- Change in Interference Score From Baseline to 6 Months(Baseline and 6 months follow-up)
- Compliance>=70% While the Patients Were in the Study(Baseline, 3 months follow-up, 6 months follow-up)
研究者
研究点 (1)
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