TAS-102 in Treating Advanced Biliary Tract Cancers

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.

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