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AMT-PET in Monitoring Telotristat Etiprate Treatment in Participants With Metastatic Well Differentiated Neuroendocrine Neoplasm

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ClinicalTrials.gov Identifier: NCT03453489
Recruitment Status : Recruiting
First Posted : March 5, 2018
Last Update Posted : February 12, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Anthony F. Shields, MD PhD, Barbara Ann Karmanos Cancer Institute

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.

Condition or disease Intervention/treatment Phase
Carcinoid Syndrome Metastatic Nonfunctional Well Differentiated Neuroendocrine Neoplasm Other: Carbon C 11 Alpha-methyltryptophan Other: Laboratory Biomarker Analysis Procedure: Positron Emission Tomography Drug: Telotristat Etiprate Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Monitoring Telotristat Ethyl Inhibition of Tryptophan Hydroxylase (TPH) in Neuroendocrine Tumors Using ?-[11C]Methyl-L-tryptophan (AMT)-PET
Actual Study Start Date : June 20, 2018
Estimated Primary Completion Date : June 1, 2020
Estimated Study Completion Date : June 1, 2020


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: Carbon C 11 Alpha-methyltryptophan
Undergo AMT-PET
Other Names:
  • 11C-alpha-methyltryptophan
  • 11C-AMT
  • [11C] AMT
  • alpha-[11C]methyl-L-tryptophan

Other: Laboratory Biomarker Analysis
Correlative studies

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:
  • LX1032 Hippurate
  • LX1606
  • LX1606 Hippurate
  • TPH Inhibitor LX1606
  • Tryptophan Hydroxylase Inhibitor LX1032
  • Tryptophan Hydroxylase Inhibitor LX1606




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Neuroendocrine tumors visibility [ Time Frame: At baseline ]
    Will be reported as proportions with two-sided exact 95% confidence intervals.

  3. 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.

  4. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histopathologically confirmed, well-?differentiated metastatic NETs
  • Documented history of carcinoid syndrome
  • Receiving stable-?dose somatostatin analog (long-?acting release [LAR], depot) for > 3 months before enrollment
  • Patients with 5-?hydroxyindoleacetic acid (HIAA) levels above or below the upper limit of normal range (normal: 0 to 15 mg/24 hours) 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
  • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or better
  • Creatinine =< 2.5 (within 14 days of PET imaging)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 14 days of PET imaging)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 ULN (within 14 days of PET imaging)
  • Patient must have a least one lesion greater than 2 cm on standard imaging (CT, MR, octreotide, or dotatate imaging) 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 on the day the prior to the first PET scan; 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 can?t be on telotristat ethyl; previous use is acceptable if the patient has been off for over one month

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03453489


Locations
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United States, Michigan
Wayne State University/Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Anthony F. Shields, M.D., PhD    313-576-8735    shieldsa@karmanos.org   
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.         
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Anthony Shields Barbara Ann Karmanos Cancer Institute

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Responsible Party: Anthony F. Shields, MD PhD, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT03453489     History of Changes
Other Study ID Numbers: 2017-144
NCI-2018-00294 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-144 ( Other Identifier: Wayne State University/Karmanos Cancer Institute )
P30CA022453 ( U.S. NIH Grant/Contract )
2017-144 ( Other Identifier: Lexicon )
First Posted: March 5, 2018    Key Record Dates
Last Update Posted: February 12, 2019
Last Verified: January 2019

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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
Additional relevant MeSH terms:
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Malignant Carcinoid Syndrome
Neuroendocrine Tumors
Serotonin Syndrome
Neoplasms
Carcinoid Tumor
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Tryptophan
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs