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

May 4, 2023 updated by: Anthony F. Shields, MD PhD, Barbara Ann Karmanos Cancer Institute

Monitoring Telotristat Ethyl Inhibition of Tryptophan Hydroxylase (TPH) in Neuroendocrine Tumors Using ?-[11C]Methyl-L-tryptophan (AMT)-PET

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

6

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Wayne State University/Karmanos Cancer Institute
        • Contact:
        • Principal Investigator:
          • Anthony F. Shields, M.D., PhD.
        • Sub-Investigator:
          • Csaba Juhasz, M.D., PhD.
        • Sub-Investigator:
          • Philip A. Philip, M.D.
        • Sub-Investigator:
          • Anteneh Tesfaye, M.D.
        • Sub-Investigator:
          • Mohammed Al Hallak, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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: Laboratory Biomarker Analysis
Correlative studies
Other: Carbon C 11 Alpha-methyltryptophan
Undergo AMT-PET
Other Names:
  • 11C-alpha-methyltryptophan
  • 11C-AMT
  • [11C] AMT
  • alpha-[11C]methyl-L-tryptophan
Procedure: Positron Emission Tomography
Undergo AMT-PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
Drug: Telotristat Etiprate
Given PO
Other Names:
  • LX1606
  • LX1032 Hippurate
  • LX1606 Hippurate
  • TPH Inhibitor LX1606
  • Tryptophan Hydroxylase Inhibitor LX1032
  • Tryptophan Hydroxylase Inhibitor LX1606

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The proportion of patients who achieved maximum standardized uptake value (SUVmax) reduction of 20% or more
Time Frame: Baseline up to follow up, assessed up to 3 months
Will be reported with a one-sided, 90% confidence limit.
Baseline up to follow up, assessed up to 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in mean standardized uptake value (SUVmean)
Time Frame: Baseline up to 3 months
Will be reported as proportions with two-sided exact 95% confidence intervals. Paired t test will be used for pre-and post-treatment SUVs if normality assumption holds.
Baseline up to 3 months
Neuroendocrine tumors visibility
Time Frame: At baseline
Will be reported as proportions with two-sided exact 95% confidence intervals.
At baseline
Optimal time frame where tumoral AMT uptake peaks
Time Frame: Up to 3 months
Will use time-activity curves. Will be reported as proportions with two-sided exact 95% confidence intervals.
Up to 3 months
Percent difference in carbon C 11 alpha-methyltryptophan (AMT) uptake between the tumor mass and background
Time Frame: Up to 3 months
Will be reported as proportions with two-sided exact 95% confidence intervals.
Up to 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Anthony Shields, Barbara Ann Karmanos Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 20, 2018

Primary Completion (Anticipated)

October 1, 2023

Study Completion (Anticipated)

October 1, 2023

Study Registration Dates

First Submitted

February 27, 2018

First Submitted That Met QC Criteria

February 27, 2018

First Posted (Actual)

March 5, 2018

Study Record Updates

Last Update Posted (Estimate)

May 5, 2023

Last Update Submitted That Met QC Criteria

May 4, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017-144 (Other Identifier: Lexicon)
  • P30CA022453 (U.S. NIH Grant/Contract)
  • NCI-2018-00294 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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