Clinical Trials /

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

NCT03790111

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 (cisplatin [cis] plus gemcitabine [gem])

Related Conditions:
  • Biliary Tract Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Safety and Efficacy Study of XERMELO® + First-line Chemotherapy in Patients With Advanced Biliary Tract Cancer
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: LX1606.1-207-BTC
  • SECONDARY ID: LX1606.207
  • SECONDARY ID: LX1606.207
  • NCT ID: NCT03790111

Conditions

  • Biliary Tract Cancer

Interventions

DrugSynonymsArms
telotristat ethyltelotristat ethyl + (cisplatin [cis] plus gemcitabine [gem])Xermelo 250mg plus 1L therapy for a week, then Xermelo 500mg

Purpose

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])

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 (cisplatin [cis] plus
      gemcitabine [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/gem) is planned.
    

Trial Arms

NameTypeDescriptionInterventions
Xermelo 250mg plus 1L therapy for a week, then Xermelo 500mgExperimentalXermelo 250mg plus 1L therapy for a week, then Xermelo 500mg plus 1L therapy for the duration of the study
  • telotristat ethyl

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) rate
Time Frame:Month 6
Safety Issue:
Description:Patient progression is defined as the time from Baseline until the first determination of PD by central radiologic at 6 months reading using RECIST v1.1 or death from any cause

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Month 6
Safety Issue:
Description:Survival at 6 months
Measure:Overall survival (OS)
Time Frame:Month 12
Safety Issue:
Description:Survival at 12 months
Measure:Progression-free survival (PFS) rate
Time Frame:Month 12
Safety Issue:
Description:Patient progression is defined as the time from Baseline until the first determination of PD by central radiologic reading using RECIST v1.1 or death from any cause at 12 months
Measure:Disease control rate (DCR)
Time Frame:Month 6
Safety Issue:
Description:Defined as complete response (CR) + partial response (PR) + stable disease (SD) at month 6
Measure:Disease control rate (DCR)
Time Frame:Month 12
Safety Issue:
Description:Defined as complete response (CR) + partial response (PR) + stable disease (SD) at month 12
Measure:Disease control rate (DCR)
Time Frame:Throug at year 2h study completion, approximately 2 years
Safety Issue:
Description:Defined as complete response (CR) + partial response (PR) + stable disease (SD) at 2 years
Measure:Objective response rate (ORR)
Time Frame:Month 6
Safety Issue:
Description:(CR) + partial response (PR) at Months 6
Measure:Objective response rate (ORR)
Time Frame:Month 12
Safety Issue:
Description:(CR) + partial response (PR) at Month 12
Measure:Objective response rate (ORR)
Time Frame:Through study completion, approximately 2 years
Safety Issue:
Description:(CR) + partial response (PR) at 2 years
Measure:Change from Baseline in plasma 5-hydroxyindoleacetic acid (5-HIAA)
Time Frame:Month 6
Safety Issue:
Description:Baseline to month 6 plasma level 5-hydroxyindoleacetic acid (5-HIAA)
Measure:Change from Baseline in plasma 5-hydroxyindoleacetic acid (5-HIAA)
Time Frame:Month 12
Safety Issue:
Description:Baseline to month 12 plasma level 5-hydroxyindoleacetic acid (5-HIAA)
Measure:Change from Baseline in plasma 5-hydroxyindoleacetic acid (5-HIAA)
Time Frame:Through study completion, approximately 2 years
Safety Issue:
Description:Baseline to month 12 plasma level 5-hydroxyindoleacetic acid (5-HIAA)
Measure:Change from Baseline in carbohydrate antigen 19-9 (CA 19-9)
Time Frame:Month 6
Safety Issue:
Description:Change from Baseline to month 6 in plasma carbohydrate antigen 19-9 (CA 19-9)
Measure:Change from Baseline in carbohydrate antigen 19-9 (CA 19-9)
Time Frame:Month 12
Safety Issue:
Description:Change from Baseline to month 12 in plasma carbohydrate antigen 19-9 (CA 19-9)
Measure:Change from Baseline in carbohydrate antigen 19-9 (CA 19-9)
Time Frame:Through study completion, approximately 2 years
Safety Issue:
Description:Change from Baseline to 2 years in plasma carbohydrate antigen 19-9 (CA 19-9)
Measure:Weight change from Baseline
Time Frame:Month 6
Safety Issue:
Description:Weight measurement
Measure:Weight change from Baseline
Time Frame:Month 12
Safety Issue:
Description:Weight measurement
Measure:Weight change from Baseline
Time Frame:Through study completion, approximately 2 years
Safety Issue:
Description:Weight measurement
Measure:Change from Baseline in plasma albumin
Time Frame:Month 6
Safety Issue:
Description:Baseline to month 6 plasma albumin levels
Measure:Change from Baseline in plasma albumin
Time Frame:Month 12
Safety Issue:
Description:Baseline to month 12 plasma albumin levels
Measure:Change from Baseline in plasma albumin
Time Frame:Through study completion, approximately 2 years
Safety Issue:
Description:Baseline to 2 years plasma albumin levels

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:TerSera Therapeutics LLC

Last Updated

October 1, 2020