Clinical trial NCT04543955: Telotristat With Lutathera in Neuroendocrine Tumors
Official title: Study of Telotristat (Xermelo) in Combination With Luetetium Lu177 Dotatate (Lutathera) in Well-Differentiated Neuroendocrine Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Neuroendocrine Tumors
Keywords: NET
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: TerSera Therapeutics LLC
First posted: 2020-09-10
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 20 months
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 6 and 12 months
measure: Median Progression-Free Survival (PFS)
timeFrame: 36 month
measure: Urinary 5-HIAA
timeFrame: Baseline and 12 months
measure: Quality of Life (QLQ-C30)
timeFrame: 20 month
measure: Quality of Life (QLQ-GI.NET21)
timeFrame: 20 month
Other outcomes:
Locations:
city: Lexington
country: United States
facility: Markey Cancer Center
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Lowell Anthony, MD
role: PRINCIPAL_INVESTIGATOR
References: