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CompletedNCT04072445Updated Aug 9, 2023Results posted

Trifluridine/Tipiracil and Irinotecan for the Treatment of Advanced Refractory Biliary Tract Cancer

A Phase 2 interventional study of Irinotecan and Irinotecan Hydrochloride in Advanced Bile Duct Carcinoma, Advanced Gallbladder Carcinoma and Refractory Bile Duct Carcinoma, sponsored by Mayo Clinic. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-08-09.

Sponsored by Mayo Clinic · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
28
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This phase II trial studies how well trifluridine/tipiracil and irinotecan work in treating patients with biliary tract cancer that has spread to other places in the body (advanced) and has not responded to treatment (refractory). Trifluridine/tipiracil and irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVE:

I. Determine the efficacy of trifluridine and tipiracil hydrochloride (trifluridine/tipiracil) in combination with irinotecan hydrochloride (irinotecan) in patients with refractory biliary tract cancers using progression-free survival (PFS) at 16 weeks.

SECONDARY OBJECTIVES:

I. Assess the safety and tolerability of trifluridine/tipiracil in combination with irinotecan in patients with refractory biliary tract cancers through adverse event monitoring.

II. Further explore the efficacy of trifluridine/tipiracil in combination with irinotecan in patients with refractory biliary tract cancers by overall response rates (ORR), disease control rates (DCR), and overall survival (OS).

CORRELATIVE RESEARCH:

I. To determine if the number of circulating tumor cells (CTCs) or the level of cell-free deoxyribonucleic acid (DNA) (cfDNA) at baseline is prognostic or predictive to the response to therapy.

II. To determine if changes in CTCs or cfDNA correlate with efficacy endpoints. III. To determine if drug response from a parallel ex vivo trial using patient-derived tumor organoid correlates with clinical response to trifluridine/tipiracil plus irinotecan.

IV. To evaluate the role of thymidine kinase 1 (TK1) in predicting the clinical benefit of trifluridine/tipiracil plus irinotecan and discover potential mechanisms of resistance using patient-derived tumor organoid and pre-treatment biopsy specimen.

EXPLORATORY RESEARCH:

I. To evaluate patients who received prior treatment with fluorouracil (5-FU) independently from the entire population in the following areas: PFS, safety and tolerability, ORR, DCR, and OS.

OUTLINE:

Patients receive trifluridine and tipiracil hydrochloride orally (PO) twice daily (BID) on days 1-5 and irinotecan hydrochloride (IV) over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for up to 2 years after study registration.

02

Conditions studied

  • Advanced Bile Duct Carcinoma
  • Advanced Gallbladder Carcinoma
  • Refractory Bile Duct Carcinoma
  • Refractory Gallbladder Carcinoma
  • Stage III Distal Bile Duct Cancer AJCC v8
  • Stage III Gallbladder Cancer AJCC v8
  • Stage III Intrahepatic Bile Duct Cancer AJCC v8
  • Stage IIIA Distal Bile Duct Cancer AJCC v8
  • Stage IIIA Gallbladder Cancer AJCC v8
  • Stage IIIA Intrahepatic Bile Duct Cancer AJCC v8
  • Stage IIIB Distal Bile Duct Cancer AJCC v8
  • Stage IIIB Gallbladder Cancer AJCC v8
  • Stage IIIB Intrahepatic Bile Duct Cancer AJCC v8
  • Stage IV Distal Bile Duct Cancer AJCC v8
  • Stage IV Gallbladder Cancer AJCC v8
  • Stage IV Intrahepatic Bile Duct Cancer AJCC v8
  • Stage IVA Gallbladder Cancer AJCC v8
  • Stage IVB Gallbladder Cancer AJCC v8
03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 28 is below the median of 45 across 5,170 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

Mayo Clinic is the lead sponsor of 3,218 studies on the registry; 670 are open to participants now.

Of its 445 completed or terminated interventional studies of FDA-regulated products, 313 (70%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

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

    • Note: Patients who have either progressed on or are intolerant to the prior therapy can be included in this study

  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

    • NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease. Disease that is measurable by physical examination only is not eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • Absolute neutrophil count (ANC) >= 1500/mm\^3 (=\< 21 days prior to registration)
  • Platelet count >= 100,000/mm\^3 (=\< 21 days prior to registration)
  • Total bilirubin =\< 1.5 x upper limit of normal (ULN) (=\< 21 days prior to registration)
  • Aspartate transaminase (AST) or alanine transaminase (ALT) =\< 3 x ULN (=\< 21 days prior to registration)
  • Creatinine =\< 1.5 x ULN (=\< 21 days prior to registration)
  • 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)
  • Willingness to provide mandatory blood and tissue specimens for correlative research

Exclusion criteria

Exclusion Criteria:

  • Any of the following because this study involves an agent that has potential genotoxic, mutagenic and teratogenic effects:

    • 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
  • Previous treatment with irinotecan or irinotecan-based chemotherapy for biliary tract cancers
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
28 participants (actual)

Study arms

  • Experimental
    Treatment (trifluridine and tipiracil, irinotecan)

    Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and irinotecan hydrochloride IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

    Drug: Irinotecan · Drug: Irinotecan Hydrochloride · Drug: Trifluridine and Tipiracil Hydrochloride

Interventions

  • DrugIrinotecan

    Given IV

  • DrugIrinotecan Hydrochloride

    Given IV

    Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, Irinotecan Hydrochloride Trihydrate, Irinotecan Monohydrochloride Trihydrate, U-101440E

  • DrugTrifluridine and Tipiracil Hydrochloride

    Given PO

    Also known as: Lonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with Trifluridine, Trifluridine/Tipiracil, Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102

06

What researchers measure

Primary outcomes

  1. Progression-free Survival (PFS)

    Will be defined as the proportion of evaluable patients who are progression-free (stable disease, partial response, complete response) at 16 weeks and assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.

    Time frame: Up to 16 weeks

Secondary outcomes

  1. Overall Response Rate (ORR)

    Will be defined as the proportion of patients who experience either a partial response or complete response as their best response. ORR will be reported descriptively and a 95% confidence interval will be reported.

    Time frame: Up to 20 months

  2. Disease Control Rate (DCR)

    Will be defined as the proportion of patients who experience a partial response, complete response, or have stable disease as their best response. DCR will be reported descriptively and a 95% confidence interval will be reported.

    Time frame: Up to 20 months

  3. PFS

    Will be determined based on RECIST v 1.1. PFS will be estimated using the Kaplan-Meier method. The median PFS and 95% confidence interval will be reported. Patients will be censored at the last disease assessment date.

    Time frame: From study entry to the first of either disease progression or death from any cause, assessed up to 20 months

  4. Overall Survival (OS)

    Will be estimated using the Kaplan-Meier method. The median OS and 95% confidence interval will be reported. Patients will be censored at the date patient was last known to be alive.

    Time frame: From study entry to death from any cause, assessed up to 20 months

  5. Number of Participants With Adverse Events

    The maximum grade for each type of adverse event by patient will be summarized by frequencies and percentages using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    Time frame: Up to 28 days

Other outcomes

  1. Circulating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (cfDNA) at Baseline

    Will determine if CTCs or cfDNA at baseline will correlate with prognosis or response to therapy.

    Time frame: Baseline

  2. Change in CTCs or cfDNA

    Will determine if change in CTCs or cfDNA will correlate with efficacy endpoints.

    Time frame: Baseline up to 20 months

  3. Correlation of Response

    Will determine if drug response from a parallel ex vivo trial using patient-derived tumor organoid correlates with clinical response to trifluridine and tipiracil hydrochloride (trifluridine/tipiracil) plus irinotecan hydrochloride (irinotecan).

    Time frame: Up to 20 months

  4. Prediction of Clinical Benefit by Thymidine Kinase 1 (TK1)

    Will evaluate the role of TK1 in predicting the clinical benefit of trifluridine/tipiracil plus irinotecan and discover potential mechanisms of resistance using patient-derived tumor organoid and pre-treatment biopsy specimen.

    Time frame: Baseline

07

Results

Posted Sep 22, 2022

Participant flow

Participant flow — Overall Study
MilestoneTreatment (Trifluridine and Tipiracil, Irinotecan)
Started28
Completed27
Not completed1

Outcome measures

PrimaryProgression-free Survival (PFS)

Will be defined as the proportion of evaluable patients who are progression-free (stable disease, partial response, complete response) at 16 weeks and assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.

Time frame:
Up to 16 weeks
Reported as:
Number · percentage of participants
Progression-free Survival (PFS)
percentage of participantsTreatment (Trifluridine and Tipiracil, Irinotecan)
Progression-free Survival (PFS)37.0 (19.4 to 57.6)
SecondaryOverall Response Rate (ORR)

Will be defined as the proportion of patients who experience either a partial response or complete response as their best response. ORR will be reported descriptively and a 95% confidence interval will be reported.

Time frame:
Up to 20 months
Reported as:
Number · percentage of participants
Overall Response Rate (ORR)
percentage of participantsTreatment (Trifluridine and Tipiracil, Irinotecan)
Overall Response Rate (ORR)20.0 (5.7 to 43.7)
SecondaryDisease Control Rate (DCR)

Will be defined as the proportion of patients who experience a partial response, complete response, or have stable disease as their best response. DCR will be reported descriptively and a 95% confidence interval will be reported.

Time frame:
Up to 20 months
Reported as:
Number · percentage of participants
Disease Control Rate (DCR)
percentage of participantsTreatment (Trifluridine and Tipiracil, Irinotecan)
Disease Control Rate (DCR)50 (27.2 to 72.8)
SecondaryPFS

Will be determined based on RECIST v 1.1. PFS will be estimated using the Kaplan-Meier method. The median PFS and 95% confidence interval will be reported. Patients will be censored at the last disease assessment date.

Time frame:
From study entry to the first of either disease progression or death from any cause, assessed up to 20 months
Reported as:
Median · months
PFS
monthsTreatment (Trifluridine and Tipiracil, Irinotecan)
PFS3.9 (2.5 to 7.4)
SecondaryOverall Survival (OS)

Will be estimated using the Kaplan-Meier method. The median OS and 95% confidence interval will be reported. Patients will be censored at the date patient was last known to be alive.

Time frame:
From study entry to death from any cause, assessed up to 20 months
Reported as:
Median · months
Overall Survival (OS)
monthsTreatment (Trifluridine and Tipiracil, Irinotecan)
Overall Survival (OS)9.1 (8.0 to 14.3)
SecondaryNumber of Participants With Adverse Events

The maximum grade for each type of adverse event by patient will be summarized by frequencies and percentages using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Time frame:
Up to 28 days
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events
ParticipantsTreatment (Trifluridine and Tipiracil, Irinotecan)
Grade 3+ AE20
Grade 4 AE4
Grade 5 AE0
Other pre-specifiedCirculating Tumor Cells (CTCs) or Cell-free Deoxyribonucleic Acid (cfDNA) at Baseline

Will determine if CTCs or cfDNA at baseline will correlate with prognosis or response to therapy.

Time frame:
Baseline

Results for this outcome have not been posted.

Other pre-specifiedChange in CTCs or cfDNA

Will determine if change in CTCs or cfDNA will correlate with efficacy endpoints.

Time frame:
Baseline up to 20 months

Results for this outcome have not been posted.

Other pre-specifiedCorrelation of Response

Will determine if drug response from a parallel ex vivo trial using patient-derived tumor organoid correlates with clinical response to trifluridine and tipiracil hydrochloride (trifluridine/tipiracil) plus irinotecan hydrochloride (irinotecan).

Time frame:
Up to 20 months

Results for this outcome have not been posted.

Other pre-specifiedPrediction of Clinical Benefit by Thymidine Kinase 1 (TK1)

Will evaluate the role of TK1 in predicting the clinical benefit of trifluridine/tipiracil plus irinotecan and discover potential mechanisms of resistance using patient-derived tumor organoid and pre-treatment biopsy specimen.

Time frame:
Baseline

Results for this outcome have not been posted.

Adverse events

Collected over 20 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Trifluridine and Tipiracil, Irinotecan)0/27 (0%)11/27 (40.7%)27/27 (100%)
Most frequent serious events
Most frequent serious events
EventTreatment (Trifluridine and Tipiracil, Irinotecan)
Biliary tract infectionInfections and infestations3/27
AscitesGastrointestinal disorders2/27
Febrile neutropeniaBlood and lymphatic system disorders1/27
Abdominal painGastrointestinal disorders1/27
DiarrheaGastrointestinal disorders1/27
Non-cardiac chest painGeneral disorders1/27
Infections and infestations - Oth specInfections and infestations1/27
SepsisInfections and infestations1/27
Intraoperative hemorrhageInjury, poisoning and procedural complications1/27
Respiratory failureRespiratory, thoracic and mediastinal disorders1/27
Most frequent other events
Showing 10 of 26
Most frequent other events
EventTreatment (Trifluridine and Tipiracil, Irinotecan)
AnemiaBlood and lymphatic system disorders26/27
Neutrophil count decreasedInvestigations18/27
Platelet count decreasedInvestigations17/27
Lymphocyte count decreasedInvestigations14/27
White blood cell decreasedInvestigations13/27
FatigueGeneral disorders9/27
DiarrheaGastrointestinal disorders6/27
NauseaGastrointestinal disorders4/27
Alkaline phosphatase increasedInvestigations4/27
HypertensionVascular disorders4/27

Baseline characteristics

Age, Continuous
Age, Continuous(years)Treatment (Trifluridine and Tipiracil, Irinotecan)
Mean64.8 ± 9.49
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Trifluridine and Tipiracil, Irinotecan)
Female15
Male13
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Treatment (Trifluridine and Tipiracil, Irinotecan)
Hispanic or Latino1
Not Hispanic or Latino27
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (Trifluridine and Tipiracil, Irinotecan)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American2
White26
More than one race0
Unknown or Not Reported0
Prior treatment
Prior treatment(Participants)Treatment (Trifluridine and Tipiracil, Irinotecan)
110
211
3+7
Primary Site of Tumor
Primary Site of Tumor(Participants)Treatment (Trifluridine and Tipiracil, Irinotecan)
Extrahepatic biliary tract cancer9
Gallbladder3
Intrahepatic16
Degree of differentiation
Degree of differentiation(Participants)Treatment (Trifluridine and Tipiracil, Irinotecan)
Moderately18
Poorly differentiated10
ECOG Performance Status (PS)
ECOG Performance Status (PS)(Participants)Treatment (Trifluridine and Tipiracil, Irinotecan)
04
124

3 further baseline measures are reported on the registry.

08

Study locations

1 site
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Apr 14, 2020

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 9, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04072445
Lead sponsor
Mayo Clinic
Collaborators
National Comprehensive Cancer Network
Responsible party
Sponsor
First posted
Aug 28, 2019
Start date
Oct 18, 2019
Primary completion
Aug 13, 2021
Completion
Aug 13, 2021
Results posted
Sep 22, 2022
Last update
Aug 9, 2023

Study contacts

Amit Mahipal
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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