Telotristat Ethyl to Promote Weight Stability in Patients With Advanced Stage Pancreatic Cancer

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.