Clinical Trials /

Telotristat With Lutathera in Neuroendocrine Tumors

NCT04543955

Description:

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

Related Conditions:
  • Neuroendocrine Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: MCC-20-GI-114-PMC
  • NCT ID: NCT04543955

Conditions

  • Neuroendocrine Tumors

Interventions

DrugSynonymsArms
Telotristat (Low-Dose)XermeloArm 1: Low-Dose Telotristat
Telotristat (High-Dose)XermeloArm 2: High-Dose Telotristat

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1: Low-Dose TelotristatExperimentalParticipants in this group will receive 750mg Telotristat per day.
  • Telotristat (Low-Dose)
Arm 2: High-Dose TelotristatExperimentalParticipants in this group will receive 1500mg Telotristat per day.
  • Telotristat (High-Dose)

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 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
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:20 months
Safety Issue:
Description:Progression-free survival at 20 months.

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:6 and 12 months
Safety Issue:
Description:Overall response rate using RECIST v1.1 at 6 and 12 months after therapy
Measure:Median Progression-Free Survival (PFS)
Time Frame:36 month
Safety Issue:
Description:Median progression-free survival.
Measure:Urinary 5-HIAA
Time Frame:Baseline and 12 months
Safety Issue:
Description:Levels of urinary 5-Hydroxyindoleacetic acid (5-HIAA) will be measured at baseline and 12 months.
Measure:Quality of Life (QLQ-C30)
Time Frame:20 month
Safety Issue:
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.
Measure:Quality of Life (QLQ-GI.NET21)
Time Frame:20 month
Safety Issue:
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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Aman Chauhan

Trial Keywords

  • NET

Last Updated

September 2, 2020