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CompletedNCT03453489Updated Apr 10, 2025Results posted

AMT-PET in Monitoring Telotristat Etiprate Treatment in Participants With MetastaticNeuroendocrine Neoplasm

A Phase 2 interventional study of Carbon C 11 Alpha-methyltryptophan and Laboratory Biomarker Analysis in Carcinoid Syndrome and Metastatic Nonfunctional Well Differentiated Neuroendocrine Neoplasm, sponsored by Barbara Ann Karmanos Cancer Institute. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-10.

Sponsored by Barbara Ann Karmanos Cancer Institute · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
4
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This pilot trial studies how well telotristat etiprate works in treating participants with well differentiated neuroendocrine neoplasm that has spread to other places in the body and monitored by carbon C 11 alpha-methyltryptophan (AMT)-emission tomography (PET). Telotristat etiprate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Studying the changes within the tumor cells via AMT-PET may help doctors better understand how tumors respond to treatment with telotristat etiprate.

Read the detailed description

PRIMARY OBJECTIVES:

I. To evaluate the effect of telotristat etiprate (telotristat ethyl) treatment in patients with advanced neuroendocrine tumors (NETs) using carbon C 11 alpha-methyltryptophan (alpha-[11C]methyl-?L-?tryptophan) (AMT)-?positron emission tomography (PET) as measured by changes in tumor maximum standardized uptake value (SUVmax).

SECONDARY OBJECTIVES:

I. Show that NETs will have increased AMT uptake on PET, as compared to surrounding non-tumor tissue at baseline.

II. Use compartmental modeling (in tumors with the left ventricle of the heart in the field-of-view) to measure change in AMT retention.

III. Measure change in AMT retention as mean standardized uptake value (SUVmean).

OUTLINE:

Participants undergo AMT-PET within 7 days prior to, and 9-14 days after start of telotristat etiprate treatment. Participants receive telotristat etiprate orally (PO) three times a day (TID) for 9-14 days.

After completion of study treatment, participants are followed up for 3 months.

02

Conditions studied

  • Carcinoid Syndrome
  • Metastatic Nonfunctional Well Differentiated Neuroendocrine Neoplasm
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Histopathologically confirmed, well-differentiated metastatic NETs
  • Receiving stable-dose somatostatin analog (long-acting release [LAR], depot) for > 3 months before enrollment.
  • Patients with 5-HIAA levels above or below the upper limit of normal range and those with unknown values at baseline are allowed to participate.
  • Able to lie within the PET scanner for at least 70 minutes while undergoing scanning.
  • ECOG performance status of 2 or better.
  • Physical exam, CBC and Multiphasic (including electrolytes, BUN, creatinine, total bilirubin, AST, and ALT) must be done within 28 days of PET imaging and demonstrate adequate renal and liver function. Creatinine ≤ 2.5, total bilirubin ≤ 1.5 x upper limit of normal (ULN). AST and ALT ≤ 2.5 ULN.
  • Patient must have a least one lesion greater than 2 cm on standard imaging (CT, MR, octreotide, or dotatate imaging within 8 weeks of the start of the study) that is judged amenable to AMT-PET.
  • Women of child bearing potential must not be pregnant or breastfeeding. A negative urine or blood pregnancy test must be obtained in women with child bearing potential. Men and women with reproductive potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) on study entry and for the duration of study participation.
  • Eligible and consent signed for imaging with AMT PET under protocol 2011-053.

Exclusion criteria

Exclusion Criteria:

  • Patients experiencing more than 12 watery bowel movements per day associated with volume contraction, dehydration, or hypotension, or showing evidence of enteric infection are excluded
  • Patients are excluded if they had undergone tumor-directed therapy within 3 months
  • Patients cannot be on a targeted agent (e.g., sunitinib or everolimus) or receiving cytotoxic chemotherapy (e.g., capecitabine or temozolomide); they cannnot be on telotristat ethyl; previous use is acceptable if the patient has been off for over one month
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
4 participants (actual)

Study arms

  • Experimental
    Treatment (AMT-PET, telotristat etiprate)

    Participants undergo AMT-PET within 7 days prior to, and 9-14 days after start of telotristat etiprate treatment. Participants receive telotristat etiprate PO TID for 9-14 days.

    Other: Carbon C 11 Alpha-methyltryptophan · Other: Laboratory Biomarker Analysis · Procedure: Positron Emission Tomography · Drug: Telotristat Etiprate

Interventions

  • OtherCarbon C 11 Alpha-methyltryptophan

    Undergo AMT-PET

    Also known as: 11C-alpha-methyltryptophan, 11C-AMT, [11C] AMT, alpha-[11C]methyl-L-tryptophan

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • ProcedurePositron Emission Tomography

    Undergo AMT-PET

    Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

  • DrugTelotristat Etiprate

    Given PO

    Also known as: LX1032 Hippurate, LX1606, LX1606 Hippurate, TPH Inhibitor LX1606, Tryptophan Hydroxylase Inhibitor LX1032, Tryptophan Hydroxylase Inhibitor LX1606

05

What researchers measure

Primary outcomes

  1. The Proportion of Patients Who Achieved SUVmax Reduction of 20% or More Between Baseline and Follow up Scan

    The proportion of patients who achieved maximum standardized uptake value (SUVmax) reduction of 20% or more between baseline and follow up scan. It will be reported with a one-sided, 90% confidence limit.

    Time frame: Baseline up to follow up, assessed up to 3 months

Secondary outcomes

  1. Change in Mean Standardized Uptake Value (SUVmean)

    Will be reported as percent change with two-sided 95% confidence intervals. Paired t test will be used for pre-and post-treatment SUVs if normality assumption holds.

    Time frame: Baseline up to 3 months

  2. Neuroendocrine Tumors Visibility

    Proportion of patients with visible neuroendocrine tumors at baseline out of total number of patients. The outcome will be reported as proportion and 95% CI

    Time frame: At baseline

  3. Difference in SUVmax of AMT Uptake Between the Tumor Mass and Background at Baseline

    Difference will be reported as percent of (SUVmax.tumor - SUVmax.background)/SUVmax.background in the baseline scan with 95% Confidence Interval

    Time frame: Baseline

06

Results

Posted Apr 10, 2025

Participant flow

Participant flow — Overall Study
MilestoneTreatment (AMT-PET, Telotristat Etiprate)
Started4
Completed4
Not completed0

Outcome measures

PrimaryThe Proportion of Patients Who Achieved SUVmax Reduction of 20% or More Between Baseline and Follow up Scan

The proportion of patients who achieved maximum standardized uptake value (SUVmax) reduction of 20% or more between baseline and follow up scan. It will be reported with a one-sided, 90% confidence limit.

Time frame:
Baseline up to follow up, assessed up to 3 months
Reported as:
Number · Proportion of participants
The Proportion of Patients Who Achieved SUVmax Reduction of 20% or More Between Baseline and Follow up Scan
Proportion of participantsTreatment (AMT-PET, Telotristat Etiprate)
The Proportion of Patients Who Achieved SUVmax Reduction of 20% or More Between Baseline and Follow up Scan0 (0 to 1)
SecondaryChange in Mean Standardized Uptake Value (SUVmean)

Will be reported as percent change with two-sided 95% confidence intervals. Paired t test will be used for pre-and post-treatment SUVs if normality assumption holds.

Time frame:
Baseline up to 3 months
Reported as:
Mean · Percentage change
Change in Mean Standardized Uptake Value (SUVmean)
Percentage changeTreatment (AMT-PET, Telotristat Etiprate)
Change in Mean Standardized Uptake Value (SUVmean)46.01 (-56.06 to 148.08)
Statistical analysis
  • Treatment (AMT-PET, Telotristat Etiprate) · t-test, 2 sided · p = 0.837
SecondaryNeuroendocrine Tumors Visibility

Proportion of patients with visible neuroendocrine tumors at baseline out of total number of patients. The outcome will be reported as proportion and 95% CI

Time frame:
At baseline
Reported as:
Number · Proportion of participants
Neuroendocrine Tumors Visibility
Proportion of participantsTreatment (AMT-PET, Telotristat Etiprate)
Neuroendocrine Tumors Visibility1 (0.51 to 1)
SecondaryDifference in SUVmax of AMT Uptake Between the Tumor Mass and Background at Baseline

Difference will be reported as percent of (SUVmax.tumor - SUVmax.background)/SUVmax.background in the baseline scan with 95% Confidence Interval

Time frame:
Baseline
Reported as:
Mean · Percentage
Difference in SUVmax of AMT Uptake Between the Tumor Mass and Background at Baseline
PercentageTreatment (AMT-PET, Telotristat Etiprate)
Difference in SUVmax of AMT Uptake Between the Tumor Mass and Background at Baseline451.90 (271.21 to 632.60)

Adverse events

Collected over From the date of informed consent until 4 weeks after the treatment completion, up to 3 months.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (AMT-PET, Telotristat Etiprate)0/4 (0%)0/4 (0%)0/4 (0%)

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Treatment (AMT-PET, Telotristat Etiprate)
<=18 years0
Between 18 and 65 years2
>=65 years2
Age, Continuous
Age, Continuous(years)Treatment (AMT-PET, Telotristat Etiprate)
Median61 (57 to 80)
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (AMT-PET, Telotristat Etiprate)
Female1
Male3
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (AMT-PET, Telotristat Etiprate)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American1
White2
More than one race0
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(participants)Treatment (AMT-PET, Telotristat Etiprate)
United States4
07

Study locations

1 site
  • Wayne State University/Karmanos Cancer Institute
    Detroit, Michigan 48201, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · May 26, 2020

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03453489
Lead sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
National Cancer Institute (NCI)
Responsible party
Anthony F. Shields, MD PhD (Principal Investigator, Barbara Ann Karmanos Cancer Institute) — Principal investigator
First posted
Mar 5, 2018
Start date
Jun 20, 2018
Primary completion
Oct 15, 2020
Completion
Oct 15, 2020
Results posted
Apr 10, 2025
Last update
Apr 10, 2025

Study contacts

Anthony Shields
principal investigator · Barbara Ann Karmanos Cancer Institute

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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