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

Primary Purpose

Carcinoid Syndrome, Metastatic Nonfunctional Well Differentiated Neuroendocrine Neoplasm

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Carbon C 11 Alpha-methyltryptophan

Laboratory Biomarker Analysis

Positron Emission Tomography

Telotristat Etiprate

About this trial

This is an interventional treatment trial for Carcinoid Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Wayne State University/Karmanos Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (AMT-PET, telotristat etiprate)

Arm Description

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.

Outcomes

Primary Outcome Measures

The proportion of patients who achieved maximum standardized uptake value (SUVmax) reduction of 20% or more

Will be reported with a one-sided, 90% confidence limit.

Secondary Outcome Measures

Change in mean standardized uptake value (SUVmean)

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.

Neuroendocrine tumors visibility

Will be reported as proportions with two-sided exact 95% confidence intervals.

Optimal time frame where tumoral AMT uptake peaks

Will use time-activity curves. Will be reported as proportions with two-sided exact 95% confidence intervals.

Percent difference in carbon C 11 alpha-methyltryptophan (AMT) uptake between the tumor mass and background

Will be reported as proportions with two-sided exact 95% confidence intervals.

Full Information

NCT ID

NCT03453489

First Posted

February 27, 2018

Last Updated

May 4, 2023

Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT03453489

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 20, 2018 (Actual)

Primary Completion Date

October 1, 2023 (Anticipated)

Study Completion Date

October 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Barbara Ann Karmanos Cancer Institute

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoid Syndrome, Metastatic Nonfunctional Well Differentiated Neuroendocrine Neoplasm

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment (AMT-PET, telotristat etiprate)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Other

Intervention Name(s)

Carbon C 11 Alpha-methyltryptophan

Other Intervention Name(s)

11C-alpha-methyltryptophan, 11C-AMT, [11C] AMT, alpha-[11C]methyl-L-tryptophan

Intervention Description

Undergo AMT-PET

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Procedure

Intervention Name(s)

Positron Emission Tomography

Other Intervention Name(s)

Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging

Intervention Description

Undergo AMT-PET

Intervention Type

Drug

Intervention Name(s)

Telotristat Etiprate

Other Intervention Name(s)

LX1032 Hippurate, LX1606, LX1606 Hippurate, TPH Inhibitor LX1606, Tryptophan Hydroxylase Inhibitor LX1032, Tryptophan Hydroxylase Inhibitor LX1606

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

The proportion of patients who achieved maximum standardized uptake value (SUVmax) reduction of 20% or more

Description

Will be reported with a one-sided, 90% confidence limit.

Time Frame

Baseline up to follow up, assessed up to 3 months

Secondary Outcome Measure Information:

Title

Change in mean standardized uptake value (SUVmean)

Description

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.

Time Frame

Baseline up to 3 months

Title

Neuroendocrine tumors visibility

Description

Will be reported as proportions with two-sided exact 95% confidence intervals.

Time Frame

At baseline

Title

Optimal time frame where tumoral AMT uptake peaks

Description

Will use time-activity curves. Will be reported as proportions with two-sided exact 95% confidence intervals.

Time Frame

Up to 3 months

Title

Percent difference in carbon C 11 alpha-methyltryptophan (AMT) uptake between the tumor mass and background

Description

Will be reported as proportions with two-sided exact 95% confidence intervals.

Time Frame

Up to 3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anthony Shields

Organizational Affiliation

Barbara Ann Karmanos Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Wayne State University/Karmanos Cancer Institute

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anthony F. Shields, M.D., PhD

Phone

313-576-8735

shieldsa@karmanos.org

First Name & Middle Initial & Last Name & Degree

Anthony F. Shields, M.D., PhD.

First Name & Middle Initial & Last Name & Degree

Csaba Juhasz, M.D., PhD.

First Name & Middle Initial & Last Name & Degree

Philip A. Philip, M.D.

First Name & Middle Initial & Last Name & Degree

Anteneh Tesfaye, M.D.

First Name & Middle Initial & Last Name & Degree

Mohammed Al Hallak, M.D.

12. IPD Sharing Statement

Learn more about this trial

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

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