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

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.

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

Primary outcomes

• The Proportion of Patients Who Achieved SUVmax Reduction of 20% or More Between Baseline and Follow up Scan [Baseline up to follow up, assessed up to 3 months]: 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.

Secondary outcomes

• Change in Mean Standardized Uptake Value (SUVmean) [Baseline up to 3 months]: 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.
• Neuroendocrine Tumors Visibility [At baseline]: 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
• Difference in SUVmax of AMT Uptake Between the Tumor Mass and Background at Baseline [Baseline]: Difference will be reported as percent of (SUVmax.tumor - SUVmax.background)/SUVmax.background in the baseline scan with 95% Confidence Interval

Sex: All, ages: 18 Years to any

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

Participant flow

Outcome results

• The Proportion of Patients Who Achieved SUVmax Reduction of 20% or More Between Baseline and Follow up Scan (Primary), Number, Proportion of participants: Treatment (AMT-PET, Telotristat Etiprate) 0 (0 to 1)
• Change in Mean Standardized Uptake Value (SUVmean) (Secondary), Mean, Percentage change: Treatment (AMT-PET, Telotristat Etiprate) 46.01 (-56.06 to 148.08) (p 0.837)
• Neuroendocrine Tumors Visibility (Secondary), Number, Proportion of participants: Treatment (AMT-PET, Telotristat Etiprate) 1 (0.51 to 1)
• Difference in SUVmax of AMT Uptake Between the Tumor Mass and Background at Baseline (Secondary), Mean, Percentage: Treatment (AMT-PET, Telotristat Etiprate) 451.90 (271.21 to 632.60)

Adverse events

Time frame: From the date of informed consent until 4 weeks after the treatment completion, up to 3 months.

• Study Protocol and Statistical Analysis Plan (PDF, 2020-05-26)

• Anthony Shields, Principal investigator, Barbara Ann Karmanos Cancer Institute

NIH grants: P30CA022453