Clinical trial NCT03278106: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-09-11
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 16-Week Progression-free Survival (PFS) Rate
timeFrame: 16 weeks
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 years
measure: Progression-free Survival (PFS)
timeFrame: Time from study entry to the first of either disease progression or death from any cause, assessed up to 3 years
measure: Overall Survival (OS)
timeFrame: Time from study entry to death from any cause, assessed up to 3 years
measure: 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)
timeFrame: Up to 3 years
Other outcomes:
measure: Change in Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (DNA) (cfDNA)
timeFrame: Baseline up to 3 years
measure: Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (DNA) (cfDNA) Analysis at Baseline
timeFrame: Baseline
measure: Mutation Status of the Tumor
timeFrame: Up to 3 years
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Amit Mahipal
role: PRINCIPAL_INVESTIGATOR
References: