Carcinoid Syndrome, Metastatic Nonfunctional Well Differentiated Neuroendocrine Neoplasm
Conditions
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.
Interventions
Undergo AMT-PET
OTHERLaboratory Biomarker Analysis
Correlative studies
PROCEDUREPositron Emission Tomography
Undergo AMT-PET
Given PO
Sponsors
National Cancer Institute (NCI)
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Carbon C 11 Alpha-methyltryptophan: Undergo AMT-PET
Laboratory Biomarker Analysis: Correlative studies
Positron Emission Tomography: Undergo AMT-PET
Telotristat Etiprate: Given PO | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Treatment (AMT-PET, Telotristat Etiprate) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 61 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
The Proportion of Patients Who Achieved SUVmax Reduction of 20% or More Between Baseline and Follow up Scan
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.
Time frame: Baseline up to follow up, assessed up to 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (AMT-PET, Telotristat Etiprate) | The Proportion of Patients Who Achieved SUVmax Reduction of 20% or More Between Baseline and Follow up Scan | 0 Proportion of participants |
Secondary
Change in Mean Standardized Uptake Value (SUVmean)
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.
Time frame: Baseline up to 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment (AMT-PET, Telotristat Etiprate) | Change in Mean Standardized Uptake Value (SUVmean) | 46.01 Percentage change |
p-value: 0.837t-test, 2 sided
Secondary
Difference in SUVmax of AMT Uptake Between the Tumor Mass and Background at Baseline
Difference will be reported as percent of (SUVmax.tumor - SUVmax.background)/SUVmax.background in the baseline scan with 95% Confidence Interval
Time frame: Baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment (AMT-PET, Telotristat Etiprate) | Difference in SUVmax of AMT Uptake Between the Tumor Mass and Background at Baseline | 451.90 Percentage |
Secondary
Neuroendocrine Tumors Visibility
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
Time frame: At baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (AMT-PET, Telotristat Etiprate) | Neuroendocrine Tumors Visibility | 1 Proportion of participants |