Description:
This trial will test the hypothesis that Telotristat treatment increases the antitumor
efficacy of Lutetium Lu 177 Dotatate therapy in neuroendocrine tumors (NETs).
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
Interventions
| Drug | Synonyms | Arms |
|---|
| Telotristat (Low-Dose) | Xermelo | Arm 1: Low-Dose Telotristat |
| Telotristat (High-Dose) | Xermelo | Arm 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
| Name | Type | Description | Interventions |
|---|
| Arm 1: Low-Dose Telotristat | Experimental | Participants in this group will receive 750mg Telotristat per day. | |
| Arm 2: High-Dose Telotristat | Experimental | Participants in this group will receive 1500mg Telotristat per day. | |
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: | Recruiting |
| Lead Sponsor: | Aman Chauhan |
Trial Keywords
Last Updated
August 10, 2021
