A Safety and Efficacy Study of XERMELO® + First-line Chemotherapy in Patients With Advanced Biliary Tract Cancer (TELE-ABC)

A Phase 2, Multicenter, Open-label, Safety and Efficacy Study of XERMELO® (Telotristat Ethyl) Plus First-line Chemotherapy in Patients With Locally Advanced, Unresectable, Recurrent or Metastatic Biliary Tract Cancer (BTC)

A Phase 2, multicenter, open-label, 2-stage study to assess the safety, tolerability, and efficacy of XERMELO in combination with first-line (1L) therapy (cisplatin [cis] plus gemcitabine [gem])

Study Overview

• Status: Terminated
• Conditions: Biliary Tract Cancer (BTC)
• Intervention / Treatment: Drug: telotristat ethyl

Detailed Description

A Phase 2, multicenter, open-label, 2-stage study to assess the safety, tolerability, and efficacy of XERMELO in combination with first-line (1L) therapy cis plus gem in patients with unresectable, locally advanced, recurrent or metastatic biliary tract cancer (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer), who are naïve to tumor-directed therapy in the locally advanced or metastatic setting, and for which treatment with 1L therapy (defined as a combination of cis plus gem) is planned.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • TerSera Investigational Site
  • California
    • Fullerton, California, United States, 92835
      • TerSera Investigational Site
  • Florida
    • Gainesville, Florida, United States, 32610
      • TerSera Investigational Site
    • Tampa, Florida, United States, 33612
      • TerSera Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • TerSera Investigational Site
  • Kansas
    • Westwood, Kansas, United States, 66205
      • TerSera Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • TerSera Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • TerSera Investigational Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • TerSera Investigational Site
  • New York
    • Buffalo, New York, United States, 14263
      • TerSera Investigational Site
    • Lake Success, New York, United States, 11042
      • TerSera Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • TerSera Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • TerSera Investigational Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • TerSera Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female adults, ≥18 years of age. Patients of childbearing potential must agree to use an adequate method of contraception during the study and for 30 days after the last dose of XERMELO
• Histopathologically or cytologically-confirmed, unresectable, locally advanced, recurrent, or metastatic biliary tract cancer (BTC)
• Naïve to tumor-directed therapy in locally advanced, unresectable, or metastatic setting
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Plans to initiate treatment with 1L therapy (cisplatin plus gemcitabine)
• Ability to provide written informed consent prior to participation in any study-related procedure

Exclusion Criteria:

• Prior exposure to XERMELO, telotristat ethyl, telotristat etiprate, LX1032, or LX1606
• Primary tumor site in the ampulla of Vater
• Treatment with photodynamic therapy for localized disease or to relieve biliary obstruction in the presence of metastatic disease within the past 30 days
• Hematology laboratory values of: a. Absolute neutrophil count (ANC) ≤1,500 cells/mm^3; or b. Platelets ≤100,000 cells/mm^3; or c. Hemoglobin (Hgb) ≤9 g/dL; or d. White blood count (WBC) ≤3,000 cells/mm^3
• Hepatic laboratory values of aspartate aminotransferase (AST) or alanine aminotransferase (ALT): a. >5 x upper limit of normal (ULN) if patient has documented history of hepatic metastases; or b. >2.5 x ULN if no liver metastases are present
• Serum albumin <2.8 g/dL
• Total bilirubin >1.5 x ULN or >1.5 mg/dL
• Prothrombin time (PT) or international normalized ratio (INR) >1.5 x ULN
• Serum creatinine or serum urea >1.5 x ULN
• Estimated glomerular filtration rate (eGFR) <50 mL/min
• Positive pregnancy test, pregnant, or breastfeeding
• Any other clinically significant laboratory abnormality that would compromise patient safety or the outcome of the study
• Any clinically significant and/or uncontrolled cardiac-related abnormality that would compromise patient safety or the outcome of the study
• Myocardial infarction within the past 6 months
• Active bleeding diathesis
• Life expectancy ≤3 months
• Current complaints of persistent constipation or history of chronic constipation, bowel obstruction or fecaloma within the past 6 months
• Receiving chronic treatment with corticosteroids ≥5 mg of prednisone per day (or equivalent) or other immunosuppressive agent(s)
• History and/or uncontrolled hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus (HIV)-1 or HIV-2
• History of substance or alcohol abuse within the past 2 years
• History of galactose intolerance, deficiency of Lapp lactase, or glucose-galactose malabsorption
• History of malignancy or active treatment for malignancy within 5 years
• Receipt of live, attenuated vaccine or close contact with someone who has received a live, attenuated vaccine within the past 1 month
• Receipt of any investigational agent or study treatment (ie, any treatment or therapy not approved by the FDA for the treatment of BTC) within the past 30 days
• Receipt of any protein or antibody-based therapeutic agents within the past 3 months
• Treatment with any tumor-directed therapy within the past 6 months with curative intent
• Existence of any surgical or medical condition that, in the judgment of the Investigator, might compromise patient safety or the outcome of the study
• Presence of any clinically significant findings (relative to the patient population) during review of medical history or upon physical exam that, in the Investigator's or Medical Monitor's opinion, would compromise patient safety or the outcome of the study
• Evidence of brain metastases
• Unable or unwilling to communicate or cooperate with the Investigator for any reason
• Employee of Sponsor or clinical site, or relative of any member of a clinical site's staff

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xermelo 250mg plus first line therapy for a week, then Xermelo 500mg; Xermelo 250 milligram (mg) plus first line therapy for a week, then Xermelo 500mg plus first line therapy for the duration of the study	Drug: telotristat ethyl; XERMELO (telotristat ethyl) tablets administered as 250 mg (1 x 250-mg tablet) three times a day plus first line therapy for 7 days, then XERMELO (telotristat ethyl) tablets administered as 500 mg (2 x 250-mg tablets) three times a day plus first line therapy for the duration of the study; Other Names: telotristat ethyl + (cisplatin [cis] plus gemcitabine [gem])

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Progression-free Survival (PFS) as Evaluated by Central Radiologist's Assessment	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions", or similar definition as accurate and appropriate.	Month 6
Project Overall Survival Rate at Month 6	Overall Survival (OS) was defined as the time from the frist dose of study treatment until the date of death due to any cause. Duration of Overall Survival (OS) in days is defined as (Date of event/censoring- date of First dose +1). Use Kaplan Meier method to project survival rate at month 6.	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall Survival (OS) was defined as the time from first dose of study treatment until the date of death due to any cause.	First dose of study treatment until the date of death due to any cause, whichever came first, a median of approximately 17.67 months
Project Overall Survival Rate at Month 12	Overall Survival (OS) was defined as the time from the first dose of study treatment until the date of death due to any cause. Duration of Overall Survival (OS) in days is defined as (Date of event/censoring - date of first dose +1). Use Kaplan Meier method to project survival rate at month 12.	12 Months
Median Progression Free Survival	Scheduled disease assessment at Cycle 19 Day 1 was used to determine PFS response rate at Month 12.	Month 12
Disease Control Rate (DCR), Central Radiologist's Assessment	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.".	Month 6
Disease Control Rate (DCR), Central Radiologist's Assessment	Disease control rate (DCR) was defined as the proportion of patients with best overall response of SD longer than 6 weeks from first dosing, confirmed PR, or confirmed CR.	Month 12
Disease Control Rate (DCR), Central Radiologist's Assessment	Disease control rate (DCR) was defined as the proportion of patients with best overall response of SD longer than 6 weeks from first dosing, confirmed PR, or confirmed CR.	End of Study up to 24 months
Overall (Objective) Response Rate (ORR), Central Radiologist's Assessment	Overall response rate (ORR) was defined as the proportion of patients with best overall response of confirmed PR or confirmed CR. The best overall response was the best overall response recorded from the start of study treatment until the EOS considering any requirement for confirmation. (CR) + partial response (PR) at Months 6	Month 6
Overall (Objective) Response Rate (ORR), Central Radiologist's Assessment	Overall response rate (ORR) was defined as the proportion of patients (Number of Responders) with best overall response of confirmed PR or confirmed CR. The best overall response was the best overall response recorded from the start of study treatment until Month 12.	Month 12
Overall (Objective) Response Rate, Central Radiologist's Assessment	Overall response rate (ORR) was defined as the proportion of patients with best overall response of confirmed PR or confirmed CR. The best overall response was the best overall response recorded from the start of study treatment until the EOS considering any requirement for confirmation.	End of Study as defined up to 24 months
Summary of Duration of Progression Free Survival, Local Radiologist's Assessment	Summary of Duration of Median Progression Free Survival, Local Radiologist's Assessment. Patient progression was defined from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 7 months.	up to 7 months
Progression Free Survival, Local Radiologist's Assessment	Summary of Median Progression Free Survival, Local Radiologist's Assessment. Defined as the time from first dose of study treatment until the first date of either disease progression or death due to any cause. Scheduled disease assessment at Cycle 19 Day 1 was used to determine PFS response rate at Month 12.	Month 12
Progression Free Survival, Local Radiologist's Assessment	Summary of Median Progression Free Survival, Local Radiologist's Assessment, End of Study	End of Study as defined up to 24 months
Overall (Objective) Response Rate, Local Read	Overall response rate (ORR) was defined as the proportion of patients with best overall response of confirmed PR or confirmed CR. The best overall response was the best overall response recorded from the start of study treatment at Month 6.	6 Months
Overall (Objective) Response Rate, Local Reader's Assessment	Overall response rate (ORR) was defined as the proportion of patients with best overall response of confirmed PR or confirmed CR. The best overall response was the best overall response recorded from the start of study treatment at Month 12.	12 Months
Overall (Objective) Response Rate (ORR), Local Reader's Assessment	Overall response rate (ORR) was defined as the proportion of patients with best overall response of confirmed PR or confirmed CR. The best overall response was the best overall response recorded from the start of study treatment until the EOS considering any requirement for confirmation.	End of Study as defined up to 24 months
Disease Control Rate (DCR), Local Reviewer	Disease control rate (DCR) was defined as the proportion of patients with best overall response of SD longer than 6 weeks from first dosing, confirmed PR, or confirmed CR.	Month 12 as defined by 1 year
Disease Control Rate (DCR), Local Reviewer	Disease control rate (DCR), Local Reviewer, 6 Months	Month 6
Disease Control Rate End of Study, Local Reviewer	Disease control rate (DCR) was defined as the proportion of patients with best overall response of SD longer than 6 weeks from first dosing, confirmed PR, or confirmed CR.	End of Study as defined up to 24 months
Mean Change From Baseline in Plasma 5-hydroxyindoleacetic Acid (5-HIAA)	Mean change from Baseline to Month 6 plasma level 5-hydroxyindoleacetic acid (5-HIAA)	Month 6
Mean Change From Baseline in Plasma 5-hydroxyindoleacetic Acid (5-HIAA)	Mean change from Baseline to Month 12 in plasma level 5-hydroxyindoleacetic Acid (5-HIAA)	Month 12
Mean Change From Baseline in Plasma 5-hydroxyindoleacetic Acid (5-HIAA)	Mean change from Baseline to End of Study in plasma 5-hydroxyindoleacetic acid (5-HIAA)	End of Study as defined up to 24 months
Change From Baseline in Carbohydrate Antigen 19-9 (CA 19-9)	Mean change from Baseline to month 6 in plasma carbohydrate antigen 19-9 (CA 19-9)	Month 6
Change From Baseline in Carbohydrate Antigen 19-9 (CA 19-9)	Mean change from Baseline to Month 12 in plasma carbohydrate antigen 19-9 (CA 19-9)	Month 12
Change From Baseline in Plasma Carbohydrate Antigen 19-9 (CA 19-9)	Mean change from Baseline to End of Study in plasma carbohydrate antigen 19-9 (CA 19-9)	End of Study as defined up to 24 months
Weight Change From Baseline	Mean change in weight at Month 6 from baseline measurement	Month 6
Weight Change From Baseline	Mean change in weight at Month 12 from baseline measurement	Month 12
Weight Change From Baseline	Mean change in weight from baseline to End of Study	End of Study as defined up to 24 months
Change From Baseline in Serum Albumin	Mean change from Baseline to Month 6 serum albumin levels	Month 6
Change From Baseline in Serum Albumin	Mean change from Baseline to Month 12 serum albumin levels	Month 12
Change From Baseline in Serum Albumin	Mean change from Baseline to End of Study serum albumin levels	End of Study as defined up to 24 months

Collaborators and Investigators

• Sponsor: TerSera Therapeutics LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2019
• Primary Completion (Actual): January 13, 2022
• Study Completion (Actual): January 13, 2022

Study Registration Dates

• First Submitted: December 25, 2018
• First Submitted That Met QC Criteria: December 27, 2018
• First Posted (Actual): December 31, 2018

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: April 17, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Cisplatin
• Other Study ID Numbers: LX1606.1-207-BTC; LX1606.207 (Other Identifier: Lexicon)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No