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Telotristat With Lutathera in Neuroendocrine Tumors

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ClinicalTrials.gov Identifier: NCT04543955
Recruitment Status : Recruiting
First Posted : September 10, 2020
Last Update Posted : November 14, 2022
TerSera Therapeutics LLC
Information provided by (Responsible Party):
Aman Chauhan, University of Kentucky

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).

Condition or disease Intervention/treatment Phase
Neuroendocrine Tumors Drug: Telotristat (Low-Dose) Drug: Telotristat (High-Dose) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Study of Telotristat (Xermelo) in Combination With Luetetium Lu177 Dotatate (Lutathera) in Well-Differentiated Neuroendocrine Tumors
Actual Study Start Date : July 19, 2021
Estimated Primary Completion Date : June 30, 2034
Estimated Study Completion Date : June 30, 2034

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Arm 1: Low-Dose Telotristat
Participants in this group will receive 750mg Telotristat per day.
Drug: Telotristat (Low-Dose)
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.
Other Name: Xermelo

Experimental: Arm 2: High-Dose Telotristat
Participants in this group will receive 1500mg Telotristat per day.
Drug: Telotristat (High-Dose)
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.
Other Name: Xermelo

Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: 20 months ]
    Progression-free survival at 20 months.

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 6 and 12 months ]
    Overall response rate using RECIST v1.1 at 6 and 12 months after therapy

  2. Median Progression-Free Survival (PFS) [ Time Frame: 36 month ]
    Median progression-free survival.

  3. Urinary 5-HIAA [ Time Frame: Baseline and 12 months ]
    Levels of urinary 5-Hydroxyindoleacetic acid (5-HIAA) will be measured at baseline and 12 months.

  4. Quality of Life (QLQ-C30) [ Time Frame: 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.

  5. Quality of Life (QLQ-GI.NET21) [ Time Frame: 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.

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04543955

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Contact: Aman Chauhan, MD 8592572862 amanchauhan@uky.edu

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United States, Kentucky
Markey Cancer Center Recruiting
Lexington, Kentucky, United States, 40536
Contact: Aman Chauhan, MD       amanchauhan@uky.edu   
Principal Investigator: Aman Chauhan, MD         
Sponsors and Collaborators
Aman Chauhan
TerSera Therapeutics LLC
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Principal Investigator: Aman Chauhan, MD University of Kentucky
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Responsible Party: Aman Chauhan, Assistant Professor, University of Kentucky
ClinicalTrials.gov Identifier: NCT04543955    
Other Study ID Numbers: MCC-20-GI-114-PMC
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: November 14, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Aman Chauhan, University of Kentucky:
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue