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

Phase 2TerminatedNCT03790111

TerSera Therapeutics LLC53 enrolled

Overview

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 \[gem\])

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Biliary Tract Cancer (BTC)

Interventions

telotristat ethylDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (14)

TerSera Investigational Site

Gilbert, Arizona, United States

TerSera Investigational Site

Fullerton, California, United States

TerSera Investigational Site

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 6 Months

Secondary Outcomes

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.

Time frame: 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.

Time frame: 12 Months

Median Progression Free Survival

Scheduled disease assessment at Cycle 19 Day 1 was used to determine PFS response rate at Month 12.

Time frame: Month 12

Disease Control Rate (DCR), Central Radiologist's Assessment

Data from ClinicalTrials.gov

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Gainesville, Florida, United States

TerSera Investigational Site

Tampa, Florida, United States

TerSera Investigational Site

Chicago, Illinois, United States

TerSera Investigational Site

Westwood, Kansas, United States

TerSera Investigational Site

Lexington, Kentucky, United States

TerSera Investigational Site

Boston, Massachusetts, United States

TerSera Investigational Site

Grand Rapids, Michigan, United States

TerSera Investigational Site

Buffalo, New York, United States

...and 4 more locations

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.".

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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: Month 12

Overall (Objective) Response Rate, Central Radiologist's Assessment

Time frame: 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.

Time frame: 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.

Time frame: Month 12

Progression Free Survival, Local Radiologist's Assessment

Summary of Median Progression Free Survival, Local Radiologist's Assessment, End of Study

Time frame: End of Study as defined up to 24 months

Overall (Objective) Response Rate, Local Read

Time frame: 6 Months

Overall (Objective) Response Rate, Local Reader's Assessment

Time frame: 12 Months

Overall (Objective) Response Rate (ORR), Local Reader's Assessment

Time frame: 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.

Time frame: Month 12 as defined by 1 year

Disease Control Rate (DCR), Local Reviewer

Disease control rate (DCR), Local Reviewer, 6 Months

Time frame: 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.

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: End of Study as defined up to 24 months

Weight Change From Baseline

Mean change in weight at Month 6 from baseline measurement

Time frame: Month 6

Weight Change From Baseline

Mean change in weight at Month 12 from baseline measurement

Time frame: Month 12

Weight Change From Baseline

Mean change in weight from baseline to End of Study

Time frame: 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

Time frame: Month 6

Change From Baseline in Serum Albumin

Mean change from Baseline to Month 12 serum albumin levels

Time frame: Month 12

Change From Baseline in Serum Albumin

Mean change from Baseline to End of Study serum albumin levels

Time frame: End of Study as defined up to 24 months