Summary

This phase II trial studies how well telotristat ethyl works in promoting weight stability in patients with pancreatic adenocarcinoma that has come back (recurrent) and spread to other places in the body (advanced). Telotristat ethyl may decrease bowel movements which may make patients gain weight. Stabilizing weight may help patients tolerate chemotherapy better and improve longevity.

Objectives

PRIMARY OBJECTIVES:
I. Weight stability after 3 and 6 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. Cycles 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. Cycles 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.

Eligibility

1. GROUP 1 (Telotristat ethyl treatment group): Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. * NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
2. GROUP 1 (Telotristat ethyl treatment group): Weight loss of 10% or more.
3. GROUP 1 (Telotristat ethyl treatment group): Age >= 18 years at the time of consent
4. GROUP 1 (Telotristat ethyl treatment group): Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 within 14 days prior to registration.
5. GROUP 1 (Telotristat ethyl treatment group): Histologic or cytological diagnosis of recurrent or metastatic pancreas adenocarcinoma (PDAC) who present for first line chemotherapy treatment for metastatic disease.
6. GROUP 1 (Telotristat ethyl treatment group): Advanced stage pancreas cancer (recurrent/metastatic).
7. GROUP 1 (Telotristat ethyl treatment group): Measurable disease determined using guidelines of Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Baseline tumor assessment should be performed using high resolution computed tomography (CT) scans or magnetic resonance imaging (MRI).
8. GROUP 1 (Telotristat ethyl treatment group): Prior systemic therapy (adjuvant or neoadjuvant setting are acceptable) if disease progressed or recurred within at least 3 months after treatment.
9. GROUP 1 (Telotristat ethyl treatment group): Estimated life expectancy of > 12 weeks, as assessed by the site investigator.
10. GROUP 1 (Telotristat ethyl treatment group): If sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods) due to unknown risk of teratogenicity.
11. GROUP 1 (Telotristat ethyl treatment group): Hemoglobin >= 8 g/dL (obtained within 7 days prior to registration).
12. GROUP 1 (Telotristat ethyl treatment group): Absolute Neutrophil Count (ANC) >= 1,500/mm^3 (obtained within 7 days prior to registration).
13. GROUP 1 (Telotristat ethyl treatment group): Platelet Count (PLT) >= 100,000/mm^3 (obtained within 7 days prior to registration).
14. GROUP 1 (Telotristat ethyl treatment group): Creatinine =< 1.5 mg/dL (obtained within 7 days prior to registration).
15. GROUP 1 (Telotristat ethyl treatment group): Albumin >= 2 g/dL (obtained within 7 days prior to registration).
16. GROUP 1 (Telotristat ethyl treatment group): Bilirubin =< 1.5 mg/dL (obtained within 7 days prior to registration).
17. GROUP 1 (Telotristat ethyl treatment group): Aspartate aminotransferase =< 3 x upper limit of normal (ULN) or < 5 x ULN in the setting of liver metastases (AST) (obtained within 7 days prior to registration).
18. GROUP 1 (Telotristat ethyl treatment group): Alanine aminotransferase (ALT) =< 3 x ULN or < 5 x ULN in the setting of liver metastases (obtained within 7 days prior to registration).
19. GROUP 1 (Telotristat ethyl treatment group): Prior radiation is allowed if happened more than 2 weeks of enrollment.
20. GROUP 2 (Non-Telotristat ethyl group): Written informed consent and HIPAA authorization for release of personal health information. * NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
21. GROUP 2 (Non-Telotristat ethyl group): Stable weight or loss of < 10% by history.
22. GROUP 2 (Non-Telotristat ethyl group): Age >= 18 years at the time of consent
23. GROUP 2 (Non-Telotristat ethyl group): ECOG Performance Status of 0-2 within 14 days prior to registration.
24. GROUP 2 (Non-Telotristat ethyl group): Histologic or cytological diagnosis of locally advanced unresectable, recurrent/metastatic PDAC who present for first line chemotherapy treatment for metastatic disease.
25. GROUP 2 (Non-Telotristat ethyl group): Advanced stage PDAC (locally advanced unresectable/recurrent/metastatic).
26. GROUP 2 (Non-Telotristat ethyl group): Prior systemic therapy (adjuvant or neoadjuvant setting are acceptable) if disease progressed or recurred within at least 3 months after treatment.
27. GROUP 2 (Non-Telotristat ethyl group): Estimated life expectancy of > 12 weeks, as assessed by the site investigator.
28. GROUP 2 (Non-Telotristat ethyl group): Prior radiation is allowed if happened more than 2 weeks of enrollment.

Treatment Sites in Georgia