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TAS-102 in Treating Advanced Biliary Tract Cancers

Primary Purpose

Cholangiocarcinoma, Stage III Gallbladder Cancer AJCC v7, Stage IIIA Gallbladder Cancer AJCC v7

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Laboratory Biomarker Analysis
Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cholangiocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histological confirmation of advanced biliary tract cancers including cancers originating in gallbladder who have received at least one line of systemic anticancer therapy;

    • Note: Patients who have either progressed or intolerant to the prior therapy can be included in this study
  • Measurable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelet count >= 100,000/mm^3
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate transaminase (AST) or alanine transaminase (ALT) =< 3 x ULN
  • Creatinine =< 1.5 x ULN
  • Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
  • Provide written informed consent
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Willing to provide blood samples for correlative research purposes

Exclusion Criteria:

  • Any of the following:

    • Pregnant persons
    • Nursing persons
    • Persons of childbearing potential who are unwilling to employ adequate contraception for at least 3 months after the last dose of the study drug
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =< 21 days prior to registration
  • Receiving any anticancer therapy for biliary tract cancer =< 21 days prior to registration
  • Other active malignancy requiring treatment in =< 6 months prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
  • History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

Sites / Locations

  • Mayo Clinic in Arizona
  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (TAS-102)

Arm Description

Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

16-Week Progression-free Survival (PFS) Rate
16-Week Progression-free survival (PFS) rate is defined as the percentage of patients who are progression-free (stable disease, partial response, or complete response as defined by RECIST v1.1 criteria) at 16 weeks post registration.

Secondary Outcome Measures

Overall Response Rate (ORR)
ORR defined as the percentage of patients who experience either a partial response or complete response by the given time point. Complete Response (CR):All of the following must be true: a. Disappearance of all target lesions. b. Each target lymph node must have reduction in short axis to <1.0 cm. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD.
Progression-free Survival (PFS)
PFS will be estimated using the Kaplan-Meier method. Progression-Free Survival (PFS) is defined as the time from study entry to the first of either disease progression or death from any cause, where disease progression will be determined based on RECIST 1.1 criteria. Patients will be censored at the last disease assessment date. The median PFS and 95% confidence interval will be reported.
Overall Survival (OS)
OS will be estimated using the Kaplan-Meier method. OS is defined as the time from study entry to death from any cause. Patients will be censored at the date patient was last known to be alive. The median OS and 95% confidence interval will be reported.
Overall Toxicity Rates (Percentages) for Grade 3 or Higher Adverse Events Considered at Least Possibly Related to Treatment, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

Full Information

First Posted
September 7, 2017
Last Updated
June 22, 2023
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03278106
Brief Title
TAS-102 in Treating Advanced Biliary Tract Cancers
Official Title
Phase II Trial of Trifluridine/Tipiracil (FTD/TPI (TAS-102)) in Biliary Tract Cancers
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
October 20, 2017 (Actual)
Primary Completion Date
November 30, 2018 (Actual)
Study Completion Date
September 16, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies how well trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) works in treating participants with biliary tract cancers that have spread to other places in the body. Drugs used in the chemotherapy, such as trifluridine/tipiracil hydrochloride combination agent TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the efficacy of trifluridine/tipiracil hydrochloride combination agent TAS-102 (FTD/TPI [TAS-102]) in patients with refractory cholangiocarcinoma using progression-free survival at 16 weeks. SECONDARY OBJECTIVES: I. Assess the safety and tolerability of FTD/TPI (TAS-102) in patients with refractory cholangiocarcinoma through adverse event monitoring. II. Further explore the efficacy of FTD/TPI (TAS-102) in patients with refractory cholangiocarcinoma by overall response rates, progression-free survival, and overall survival. TERTIARY OBJECTIVES: I. Determine if circulating tumor cells (CTCs) or cell-free deoxyribonucleic acid (DNA) (cfDNA) at baseline correlates with prognosis or response to therapy. II. Determine if change in CTCs or cfDNA correlates with efficacy endpoints. III. Determine if different mutational status of the tumor will affect efficacy endpoints. OUTLINE: Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally (PO) twice daily (BID) on days 1-5 and 8-12. 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 and then every 3 months for up to 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholangiocarcinoma, Stage III Gallbladder Cancer AJCC v7, Stage IIIA Gallbladder Cancer AJCC v7, Stage IIIB Gallbladder Cancer AJCC v7, Stage IV Gallbladder Cancer AJCC v7, Stage IVA Gallbladder Cancer AJCC v7, Stage IVB Gallbladder Cancer AJCC v7

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (TAS-102)
Arm Type
Experimental
Arm Description
Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally PO BID on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102
Other Intervention Name(s)
Lonsurf, TAS-102, Trifluridine/Tipiracil
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
16-Week Progression-free Survival (PFS) Rate
Description
16-Week Progression-free survival (PFS) rate is defined as the percentage of patients who are progression-free (stable disease, partial response, or complete response as defined by RECIST v1.1 criteria) at 16 weeks post registration.
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
ORR defined as the percentage of patients who experience either a partial response or complete response by the given time point. Complete Response (CR):All of the following must be true: a. Disappearance of all target lesions. b. Each target lymph node must have reduction in short axis to <1.0 cm. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD.
Time Frame
Up to 3 years
Title
Progression-free Survival (PFS)
Description
PFS will be estimated using the Kaplan-Meier method. Progression-Free Survival (PFS) is defined as the time from study entry to the first of either disease progression or death from any cause, where disease progression will be determined based on RECIST 1.1 criteria. Patients will be censored at the last disease assessment date. The median PFS and 95% confidence interval will be reported.
Time Frame
Time from study entry to the first of either disease progression or death from any cause, assessed up to 3 years
Title
Overall Survival (OS)
Description
OS will be estimated using the Kaplan-Meier method. OS is defined as the time from study entry to death from any cause. Patients will be censored at the date patient was last known to be alive. The median OS and 95% confidence interval will be reported.
Time Frame
Time from study entry to death from any cause, assessed up to 3 years
Title
Overall Toxicity Rates (Percentages) for Grade 3 or Higher Adverse Events Considered at Least Possibly Related to Treatment, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
Description
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
Time Frame
Up to 3 years
Other Pre-specified Outcome Measures:
Title
Change in Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (DNA) (cfDNA)
Description
Will correlate with efficacy endpoints.
Time Frame
Baseline up to 3 years
Title
Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (DNA) (cfDNA) Analysis at Baseline
Description
Will determine if CTCs or cfDNA at baseline will correlate with prognosis or response to therapy.
Time Frame
Baseline
Title
Mutation Status of the Tumor
Description
Will determine if different mutations status of the tumor will affect efficacy endpoints.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histological confirmation of advanced biliary tract cancers including cancers originating in gallbladder who have received at least one line of systemic anticancer therapy; Note: Patients who have either progressed or intolerant to the prior therapy can be included in this study Measurable disease Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 Absolute neutrophil count (ANC) >= 1500/mm^3 Platelet count >= 100,000/mm^3 Total bilirubin =< 1.5 x upper limit of normal (ULN) Aspartate transaminase (AST) or alanine transaminase (ALT) =< 3 x ULN Creatinine =< 1.5 x ULN Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only Provide written informed consent Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study) Willing to provide blood samples for correlative research purposes Exclusion Criteria: Any of the following: Pregnant persons Nursing persons Persons of childbearing potential who are unwilling to employ adequate contraception for at least 3 months after the last dose of the study drug Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm =< 21 days prior to registration Receiving any anticancer therapy for biliary tract cancer =< 21 days prior to registration Other active malignancy requiring treatment in =< 6 months prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amit Mahipal
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Learn more about this trial

TAS-102 in Treating Advanced Biliary Tract Cancers

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