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Telotristat With Lutathera in Neuroendocrine Tumors

Primary Purpose

Neuroendocrine Tumors

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Telotristat (Low-Dose)
Telotristat (High-Dose)
Sponsored by
Lowell Anthony, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroendocrine Tumors focused on measuring NET

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 AEs of previously administered therapeutic agents to Grade 2 or less toxicity according to CTCAE version 5.0
  • 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
  • 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

Sites / Locations

  • Markey Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1: Low-Dose Telotristat

Arm 2: High-Dose Telotristat

Arm Description

Participants in this group will receive 750mg Telotristat per day.

Participants in this group will receive 1500mg Telotristat per day.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Overall Response Rate (ORR)
Overall response rate using RECIST v1.1 at 6 and 12 months after therapy
Median Progression-Free Survival (PFS)
Median progression-free survival.
Urinary 5-HIAA
Levels of urinary 5-Hydroxyindoleacetic acid (5-HIAA) will be measured at baseline and 12 months.
Quality of Life (QLQ-C30)
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.
Quality of Life (QLQ-GI.NET21)
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.

Full Information

First Posted
September 2, 2020
Last Updated
June 2, 2023
Sponsor
Lowell Anthony, MD
Collaborators
TerSera Therapeutics LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04543955
Brief Title
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor cancelled research
Study Start Date
September 13, 2021 (Actual)
Primary Completion Date
June 3, 2022 (Actual)
Study Completion Date
June 3, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Lowell Anthony, MD
Collaborators
TerSera Therapeutics LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Tumors
Keywords
NET

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Low-Dose Telotristat
Arm Type
Experimental
Arm Description
Participants in this group will receive 750mg Telotristat per day.
Arm Title
Arm 2: High-Dose Telotristat
Arm Type
Experimental
Arm Description
Participants in this group will receive 1500mg Telotristat per day.
Intervention Type
Drug
Intervention Name(s)
Telotristat (Low-Dose)
Other Intervention Name(s)
Xermelo
Intervention Description
Participants in this group will receive Lutetium Lu 177 Dotate (Lutathera) by IV every 2 months (Q8weeks) for a total of 4 doses. They will also receive oral Telotristat at 750mg per day (250mg TID) for 20 months.
Intervention Type
Drug
Intervention Name(s)
Telotristat (High-Dose)
Other Intervention Name(s)
Xermelo
Intervention Description
Participants in this group will receive Lutetium Lu 177 Dotate (Lutathera) by IV every 2 months (Q8weeks) for a total of 4 doses. They will also receive oral Telotristat at 1500mg per day (500mg TID) for 20 months.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
Progression-free survival at 20 months.
Time Frame
20 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
Overall response rate using RECIST v1.1 at 6 and 12 months after therapy
Time Frame
6 and 12 months
Title
Median Progression-Free Survival (PFS)
Description
Median progression-free survival.
Time Frame
36 month
Title
Urinary 5-HIAA
Description
Levels of urinary 5-Hydroxyindoleacetic acid (5-HIAA) will be measured at baseline and 12 months.
Time Frame
Baseline and 12 months
Title
Quality of Life (QLQ-C30)
Description
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.
Time Frame
20 month
Title
Quality of Life (QLQ-GI.NET21)
Description
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.
Time Frame
20 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lowell Anthony, MD
Organizational Affiliation
University of Kentucky
Official's Role
Principal Investigator
Facility Information:
Facility Name
Markey Cancer Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Telotristat With Lutathera in Neuroendocrine Tumors

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