Neuroendocrine TumorsPhase 2NCT04543955
Telotristat With Lutathera in Neuroendocrine Tumors
A Phase 2 study testing Telotristat (Low-Dose) and Telotristat (High-Dose) in people with Neuroendocrine Tumors, run by Lowell Anthony, MD at 1 site in United States.
Trial summary
This trial will test the hypothesis that Telotristat treatment increases the antitumor efficacy of Lutetium Lu 177 Dotatate therapy in neuroendocrine tumors (NETs). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Neuroendocrine Tumors
- What is being tested?
- Telotristat (Low-Dose) and Telotristat (High-Dose)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Sep 2021to 3 Jun 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of Telotristat (Xermelo) in Combination With Luetetium Lu177 Dotatate (Lutathera) in Well-Differentiated Neuroendocrine Tumors
This trial will test the hypothesis that Telotristat treatment increases the antitumor efficacy of Lutetium Lu 177 Dotatate therapy in neuroendocrine tumors (NETs).
Read the 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.
- Conditions
- Neuroendocrine Tumors
- Being tested
- Telotristat (Low-Dose), Telotristat (High-Dose)
- Keywords
- NET
- Medical subject headings
- Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Telotristat (Low-Dose)Drug
Also called Xermelo
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.
Telotristat (High-Dose)Drug
Also called Xermelo
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Low-Dose Telotristat | Experimental | Participants in this group will receive 750mg Telotristat per day. Receives: Drug: Telotristat (Low-Dose) |
| Arm 2: High-Dose Telotristat | Experimental | Participants in this group will receive 1500mg Telotristat per day. Receives: Drug: Telotristat (High-Dose) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS)
Progression-free survival at 20 months.
Measured: 20 months
Secondary outcomes (5)
Overall Response Rate (ORR)
Overall response rate using RECIST v1.1 at 6 and 12 months after therapy
Measured: 6 and 12 months
Median Progression-Free Survival (PFS)
Median progression-free survival.
Measured: 36 month
Urinary 5-HIAA
Levels of urinary 5-Hydroxyindoleacetic acid (5-HIAA) will be measured at baseline and 12 months.
Measured: 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.
Measured: 20 month
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.
Measured: 20 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2020
- Study start13 Sep 2021
- Primary completion3 Jun 2022
- Study completion3 Jun 2022
Why it stopped: Sponsor cancelled research
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neuroendocrine TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lowell Anthony, MD
- Sponsor type
- University, hospital or other
- Collaborators
- TerSera Therapeutics LLC
- Responsible party
- Sponsor-investigator, Lowell Anthony, MD, University of Kentucky
- Investigators
- Lowell Anthony, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04543955
- Sponsor's protocol ID
- MCC-20-GI-114-PMC
- Status last verified
- Jun 2023
- First submitted
- 2 Sep 2020
- Last updated
- 27 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Telotristat (Xermelo) in Combination With Luetetium Lu177 Dotatate (Lutathera) in Well-Differentiated Neuroendocrine Tumors
- ClinicalTrials.gov ID
- NCT04543955
- Acronym / sponsor ID
- MCC-20-GI-114-PMC
- Conditions
- Neuroendocrine Tumors
- Keywords
- NET
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor cancelled research
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Lowell Anthony, MDUniversity, hospital or other
- Collaborators
- TerSera Therapeutics LLC
- Study start
- 13 Sep 2021 (actual)
- Primary completion
- 3 Jun 2022 (actual)
- Study completion
- 3 Jun 2022 (actual)
- First posted
- 10 Sep 2020 (actual)
- Results
- Posted 27 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Low-Dose Telotristat | Experimental | Drug: Telotristat (Low-Dose)Participants in this group will receive 750mg Telotristat per day. |
| Arm 2: High-Dose Telotristat | Experimental | Drug: Telotristat (High-Dose)Participants in this group will receive 1500mg Telotristat per day. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Telotristat (Low-Dose)Also: XermeloParticipants 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. | Drug | Arm 1: Low-Dose Telotristat |
| Telotristat (High-Dose)Also: XermeloParticipants 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. | Drug | Arm 2: High-Dose Telotristat |
Primary outcome
Progression-Free Survival (PFS)
Time frame: 20 months
Progression-free survival at 20 months.
5 secondary outcomes
Overall Response Rate (ORR)
Time frame: 6 and 12 months
Median Progression-Free Survival (PFS)
Time frame: 36 month
Urinary 5-HIAA
Time frame: Baseline and 12 months
Quality of Life (QLQ-C30)
Time frame: 20 month
Quality of Life (QLQ-GI.NET21)
Time frame: 20 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lowell Anthony, MD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Telotristat (Low-Dose) and Telotristat (High-Dose) in people with Neuroendocrine Tumors, run by Lowell Anthony, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) (time frame: 20 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2023.