Telotristat With Lutathera in Neuroendocrine Tumors

Phase 2

Terminated

Conditions: Neuroendocrine Tumors

Interventions: Drug: Telotristat (Low-Dose)
Drug: Telotristat (High-Dose)

Registration Number: NCT04543955

Lead Sponsor: Lowell Anthony, MD

Brief Summary: This trial will test the hypothesis that Telotristat treatment increases the antitumor efficacy of Lutetium Lu 177 Dotatate therapy in neuroendocrine tumors (NETs).

Detailed Description: Neuroendocrine tumors (NETs) are a very heterogeneous group of tumors that develop predominantly in the gastrointestinal and pulmonary systems. Clinical detection and diagnosis are more reliable at late stages when metastatic spread has occurred. Patients with advanced disease may suffer from complications of uncontrolled hormone secretion and usually succumb due to tumor progression.

This trial tests the hypothesis that inhibition of serotonin production with Telotristat will lead to cytostatic effects on neuroendocrine tumors and will complement the anti-tumor activity of Lutetium 177 Dotatate. The proposed combination may result in improved treatment efficacy as reflected by improved 20-month progression-free survival (PFS) as compared to historical control.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

Inclusion Criteria

Metastatic, or unresectable, histologically confirmed well-differentiated grade 1 and 2 neuroendocrine tumor with a positive gallium 68 Dotatate scan within 6 months prior to study enrollment
Baseline CT scan or MRI with measurable progressive disease based on RECIST Criteria
Failure of at least one prior systemic cancer treatment for this diagnosis
Recovered from Adverse Events of previously administered therapeutic agents to Grade 2 or less toxicity according to CTCAE version 5.0
Eastern Cooperative Oncology Group (ECOG) performance status ≤2
normal organ and marrow function

Exclusion Criteria

Prior exposure to Lutetium Lu 177 Dotatate
History of allergic reactions attributed to compounds of similar chemical or biologic composition to Telotristat or Lutetium Lu 177 Dotatate.
Presence of unstable angina or myocardial infarction
New York Heart Association (NYHA) Class III or IV heart failure
uncontrolled angina
history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities
Pregnant or lactating women
Women of childbearing potential or male patients of reproductive potential
Any other significant medical or psychiatric condition, currently uncontrolled by treatment, which may interfere with completion of the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Low-Dose Telotristat	Telotristat (Low-Dose)	Participants in this group will receive 750mg Telotristat per day.
Arm 2: High-Dose Telotristat	Telotristat (High-Dose)	Participants in this group will receive 1500mg Telotristat per day.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	20 months	Progression-free survival at 20 months.

Secondary Outcome Measures

Name	Time	Method
Median Progression-Free Survival (PFS)	36 month	Median progression-free survival.
Quality of Life (QLQ-C30)	20 month	The Quality of Life Questionnaire C30 (QLQ-C30) was developed by the European Organization for Research and Treatment of Cancer (EORTC) to assess quality of life in cancer patients.It includes five function domains (physical, emotional, social, role, cognitive), eight symptoms (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia, dyspnea, and appetite loss), as well as global health/quality-of-life and financial impact. Subjects respond on a four-point scale from "not at all" to "very much" for most items.Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function and higher levels of symptom burden.
Overall Response Rate (ORR)	6 and 12 months	Overall response rate using RECIST v1.1 at 6 and 12 months after therapy
Quality of Life (QLQ-GI.NET21)	20 month	The Quality of Life GI Neuroendocrine Tumor survey (QLQ-GINET21) contains a total of 21 items: four single-item assessments relating to muscle and/or bone pain (MBP), body image (BI), information (INF) and sexual functioning (SX), together with 17 items organised into five proposed scales: endocrine symptoms (ED; three items), GI symptoms (GI; five items), treatment-related symptoms (TR; three items), social functioning (SF) and disease-related worries (DRW; three items). The response format of the questionnaire is a four-point Likert scale. Responses are linearly transformed to a 0-100 scale using EORTC guidelines, with higher scores reflecting more severe symptoms.
Urinary 5-HIAA	Baseline and 12 months	Levels of urinary 5-Hydroxyindoleacetic acid (5-HIAA) will be measured at baseline and 12 months.