Clinical Trials /

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

NCT04072445

Description:

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.

Related Conditions:
  • Biliary Tract Carcinoma
  • Gallbladder Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trifluridine/Tipiracil and Irinotecan for the Treatment of Advanced Refractory Biliary Tract Cancer
  • Official Title: Phase II Trial of Trifluridine/Tipiracil in Combination With Irinotecan in Biliary Tract Cancers

Clinical Trial IDs

  • ORG STUDY ID: MC1941
  • SECONDARY ID: NCI-2019-05653
  • SECONDARY ID: MC1941
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT04072445

Conditions

  • 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

Interventions

DrugSynonymsArms
IrinotecanTreatment (trifluridine and tipiracil, irinotecan)
Irinotecan HydrochlorideCampto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, Irinotecan Hydrochloride Trihydrate, Irinotecan Monohydrochloride Trihydrate, U-101440ETreatment (trifluridine and tipiracil, irinotecan)
Trifluridine and Tipiracil HydrochlorideLonsurf, TAS 102, TAS-102, Tipiracil Hydrochloride Mixture with Trifluridine, Trifluridine/Tipiracil, Trifluridine/Tipiracil Hydrochloride Combination Agent TAS-102Treatment (trifluridine and tipiracil, irinotecan)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (trifluridine and tipiracil, irinotecan)ExperimentalPatients 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.
  • Irinotecan
  • Irinotecan Hydrochloride
  • Trifluridine and Tipiracil Hydrochloride

Eligibility Criteria

        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:

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:Up to 16 weeks
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Disease control rate (DCR)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:PFS
Time Frame:From study entry to the first of either disease progression or death from any cause, assessed up to 2 years
Safety Issue:
Description: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.
Measure:Overall survival (OS)
Time Frame:From study entry to death from any cause, assessed up to 2 years
Safety Issue:
Description: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.
Measure:Incidence of adverse events
Time Frame:Up to 28 days
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

Last Updated

October 24, 2019