This phase II trial studies how well telotristat ethyl works in promoting weight stability in patients with pancreatic adenocarcinoma that has come back and spread to other places in the body. Telotristat ethyl may decrease bowel movements which may make patients gain weight. Stabilizing weight may help patients tolerate chemotherapy better and improve longevity.
PRIMARY OBJECTIVES: I. Evaluate weight stability after 3 months of telotristat ethyl treatment in patients who have significant weight loss (documented to be more than or equal to 10%) prior to the start of treatment. (Group 1). II. Evaluate the change in serum and 24-hours (hr) urine 5-hydroxyindoleacetic acid (5-HIAA) in patients with locally advanced unresectable, recurrent or metastatic pancreatic adenocarcinoma (PDAC) receiving chemotherapy. (Group 2). SECONDARY OBJECTIVES: I. Evaluate the impact of weight stabilization/gain on patients in Group 1 on performance status, quality of life (QOL), mid arm circumference (MAC) and muscle mass on cross sectional imaging. II. Evaluate correlations between changes in serotonin/ 5HIAA levels on radiologic response, weight stability, mid arm circumference (MAC), and muscle mass on cross sectional imaging. III. Evaluate the relation of baseline serum and 24-hr urine 5-HIAA on weight loss in patients with advanced PDAC. IV. Safety and tolerability of telotristat ethyl with gemcitabine/nab-paclitaxel combination chemotherapy. V. Evaluate response rate (RR) assessed per Response Evaluation Criteria in Solid Tumors (RECIST), progression free survival and overall survival in patients receiving telotristat ethyl (Group 1). OUTLINE: Patients are randomized to 1 of 2 groups. GROUP 1: Patients receive gemcitabine/nab-paclitaxel combination chemotherapy on days 1, 8 and 15, and telotristat ethyl orally (PO) once daily (QD), twice daily (BID), or thrice daily (TID) on days 1 and 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. GROUP 2: Patients receive chemotherapy (at the discretion of the investigator) on days 1, 8 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, then every 8 weeks thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
23
Given gemcitabine/nab-paclitaxel combination therapy
Given gemcitabine/nab-paclitaxel combination therapy
Given PO
Emory University Hospital Midtown
Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, United States
Weight Stability
Weight stability will be documented as percent weight change at 3 months compared to baseline.
Time frame: Baseline up to 3 months after study start
Change in 24-hr Urine 5-hydroxyindoleacetic Acid (5-HIAA) Levels
The change will be summarized as mean and standard deviation.
Time frame: Baseline up to 4 months after study start
Mid Arm Circumference (MAC) Measured in cm
Mid arm circumference (MAC) will be reviewed on cross sectional imaging and will be assessed with imaging guided measurements of the psoas and rectus abdominis muscle.
Time frame: Up to 2 years after study start
Quality of Life (QOL)
Quality of life (QOL) will be assessed by the Obesity Related Quality of Life (OWL-QOL)-17 questionnaire. \*Please note OC Measure was not collected.
Time frame: Up to 2 years after study start
Blood Serotonin Levels
Blood serotonin levels will be compared in the 2 groups.
Time frame: Up to 2 years after study start
Response Rate (RR)
Response rate (RR) will be assessed per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, in patients receiving telotristat ethyl (Group 1).
Time frame: Up to 2 years after study start
Median Overall Survival (MOS)
Median overall survival (MOS) will be measured using the Kaplan-Meier method.
Time frame: Up to 2 years after study start
Duration of Response
Duration of response will be estimated from time of documentation of response to time of progression and will be evaluated by computed tomography/magnetic resonance imaging scans of the organ(s) with the target lesion(s) based on RECIST criteria.
Time frame: Up to 2 years after study start
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