Clinical Trials /

Study of TRIFLURIDINE/TIPIRACIL in Previously Treated Cholangiocarcinoma

NCT04076761

Description:

This is a multi-centre, open-label, single arm phase 2 study to assess the efficacy of TRIFLURIDINE/TIPIRACIL, in patients with advanced cholangiocarcinoma as measured by median progression-free survival (PFS). This study will enroll a total of 47 patients over a 12-month period, according to a two stage enrollment design. Nine patients will be enrolled during the first stage and the trial will be terminated if 4 or more out of the 9 have disease progression. If the trial goes on to the second stage, a total of 47 patients (38 in second stage) will be required. Patients will be seen prior to enrolment (within 28 days of treatment), every 4 weeks while on treatment, at the end of treatment, and 30 days post-treatment. Patients will remain on long-term follow-up and will be seen every 12 weeks (+/- 14 days) until 1 year post-treatment when they will enter into the survival follow-up period and will be contacted every 12 weeks by phone until progression or toxicity.

Related Conditions:
  • Cholangiocarcinoma
  • Gallbladder Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of TRIFLURIDINE/TIPIRACIL in Previously Treated Cholangiocarcinoma
  • Official Title: A Multi-Centre, Open-Label Phase 2 Study of TRIFLURIDINE/TIPIRACIL in Previously Treated Cholangiocarcinoma (The MOCHA Trial)

Clinical Trial IDs

  • ORG STUDY ID: CTO 1645
  • NCT ID: NCT04076761

Conditions

  • Cholangiocarcinoma
  • Bile Duct Cancer

Interventions

DrugSynonymsArms
Trifluridine/TipiracilFTD/TPI, LonsurfTrifluridine/Tipiracil

Purpose

This is a multi-centre, open-label, single arm phase 2 study to assess the efficacy of TRIFLURIDINE/TIPIRACIL, in patients with advanced cholangiocarcinoma as measured by median progression-free survival (PFS). This study will enroll a total of 47 patients over a 12-month period, according to a two stage enrollment design. Nine patients will be enrolled during the first stage and the trial will be terminated if 4 or more out of the 9 have disease progression. If the trial goes on to the second stage, a total of 47 patients (38 in second stage) will be required. Patients will be seen prior to enrolment (within 28 days of treatment), every 4 weeks while on treatment, at the end of treatment, and 30 days post-treatment. Patients will remain on long-term follow-up and will be seen every 12 weeks (+/- 14 days) until 1 year post-treatment when they will enter into the survival follow-up period and will be contacted every 12 weeks by phone until progression or toxicity.

Trial Arms

NameTypeDescriptionInterventions
Trifluridine/TipiracilExperimentalFTD/TPI at 35 mg/m2 (based on BSA) that is administered in tablet form, orally, twice daily, within one hour of morning and evening meals, on days 1-5 and days 8-12 of a 28 day cycle.
  • Trifluridine/Tipiracil

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically documented locally advanced or metastatic biliary tract cancer (intra
             or extrahepatic cholangiocarcinoma or gallbladder cancer) previously treated with
             first line standard chemotherapy (gemcitabine-based chemotherapy at least one cycle).
             Patients who develop a recurrence after adjuvant capecitabine therapy must have
             subsequently received at least one cycle of a gemcitabine-based therapy to be
             eligible. Patients who have received gemcitabine in the adjuvant setting but
             progressed within 6 months of their last cycle will be eligible for the study.

          2. Presence of measurable disease as assessed by CT scan of the chest, abdomen and pelvis
             based on RECIST 1.1.

          3. ECOG performance status of 0 or 1.

          4. Expected life expectancy of ≥ 3 months.

          5. Age 18 years and above

          6. Able to swallow and retain oral medication.

          7. Adequate hematologic function defined by the following laboratory parameter:

               1. Hemoglobin ≥ 9g/dL

               2. Absolute neutrophil count ≥1.5 x 109/L

               3. Platelet count ≥75x 109/L

          8. Adequate hepatic and renal function as defined by:

               1. AST and ALT ≤ 3.0 X ULN (≤ 5 if liver metastasis present)

               2. Total bilirubin ≤ 1.5X ULN

               3. Calculated creatinine clearance ≥50 ml/min using Cockcroft-Gault formula

          9. Patients who have treated brain metastasis (via local radiation standards or surgical
             resection or local techniques) and who are either off steroids or on a stable dose of
             steroids for at least one month (30 days), AND who are off anticonvulsants, AND have
             radiological documented stability of lesions for at least 3 months may be eligible.

         10. Patients must have the ability to read, understand, and sign an informed consent and
             must be willing to comply with study treatment and procedures.

        Exclusion Criteria:

          1. Any malignancy related to HIV, history of HIV, history of known HBV surface antigen
             positivity (subjects with documented laboratory evidence of HBV clearance may be
             enrolled) or positive HCV antibody. Testing for these diseases is not mandatory unless
             clinically indicated

          2. Chemotherapy, radiotherapy, immunotherapy, or other anti-cancer therapy including
             investigational drugs within 28 days prior to enrolment.

          3. Patients with unresolved Grade 3/4 toxicities from prior therapies.

          4. Any major surgery within the last four weeks.

          5. Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of
             the cervix or uterus or non-melanoma skin cancer or in-situ carcinoma of the prostate
             (Gleason score ≤ 7, with all treatment being completed 6 months prior to enrollment,
             unless at least 5 years have elapsed since last treatment and the patient is
             considered cured)

          6. Patients with locally or centrally known FGFR2 fusion (Sunnybrook, Ottawa and PMCC
             sites only).

          7. Female patients of childbearing potential and men able to father children who do not
             agree to use adequate methods of contraception from time of enrolment until 6 months
             after the last date of treatment administration.

          8. Women who are breastfeeding

          9. Patients with suspected or documented leptomeningeal disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Median progression-free survival (PFS)
Time Frame:From enrolment until the date of objective radiological disease progression according to RECIST v1.1 or death (by any cause in the absence of progression) up to 1 year
Safety Issue:
Description:As measured on the basis of RECIST v1.1 criteria

Secondary Outcome Measures

Measure:Safety and tolerability of FTD/TPI: CTCAE version 5.0
Time Frame:Day 1 of each new treatment cycle (each cycle is 28 days), and at the end of treatment visit (up to 1 year after enrolment)
Safety Issue:
Description:Assessed by using CTCAE version 5.0 and tolerability
Measure:Disease Control Rate (Complete Response, Partial Response, Stable Disease) of FTD/TPI
Time Frame:From enrolment until the date of objective radiological disease progression according to RECIST v1.1 or death (by any cause in the absence of progression) up to 1 year
Safety Issue:
Description:As measured on the basis of RECIST v1.1 criteria
Measure:Duration of response of FTD/TPI
Time Frame:From enrolment until the date of objective radiological disease progression according to RECIST v1.1 or death (by any cause in the absence of progression) up to 1 year
Safety Issue:
Description:As measured on the basis of RECIST v1.1 criteria
Measure:Median overall survival of patients with cholangiocarcinoma treated with FTD/TPI.
Time Frame:From enrolment until the date of objective radiological disease progression according to RECIST v1.1 or death (by any cause in the absence of progression) up to 1 year
Safety Issue:
Description:As measured on the basis of RECIST v1.1 criteria
Measure:Quality of life: European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30
Time Frame:Baseline, and Day 1 of each new treatment cycle (each cycle is 28 days), and at the end of treatment visit (up to 1 year after enrolment)
Safety Issue:
Description:As measured by the European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ C30) Functioning, symptoms, and global health status scores will be calculated, graphed, and summarized at baseline and each follow-up visit. General linear mixed model will be conducted to detect significant changing over time for functioning, symptoms and global health status scores. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sunnybrook Health Sciences Centre

Trial Keywords

  • Cholangiocarcinoma
  • Bile Duct Cancer
  • FTD/TPI
  • TRIFLURIDINE/TIPIRACIL

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