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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Carcinoid Syndrome, Metastatic Nonfunctional Well Differentiated Neuroendocrine Neoplasm

Intervention / Treatment
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* Other: Carbon C 11 Alpha-methyltryptophan
* Other: Laboratory Biomarker Analysis
* Procedure: Positron Emission Tomography
* Drug: Telotristat Etiprate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (AMT-PET, telotristat etiprate)<br>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<br>* Undergo AMT-PET<br>* Other names: alpha-[11C]methyl-L-tryptophan;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Positron Emission Tomography<br>* Undergo AMT-PET<br>* Other names: proton magnetic resonance spectroscopic imaging;Drug: Telotristat Etiprate<br>* Given PO<br>* Other names: Tryptophan Hydroxylase Inhibitor LX1606;|

What is the study measuring?
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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 | 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) | 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 | Will be reported as proportions with two-sided exact 95% confidence intervals. | At baseline | 
| 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. | Up to 3 months | 
| 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. | Up to 3 months |