Study of TRIFLURIDINE/TIPIRACIL in Previously Treated Cholangiocarcinoma

Phase 2

Terminated

• Conditions: Cholangiocarcinoma; Bile Duct Cancer
• Interventions: Drug: Trifluridine/Tipiracil

• Registration Number: NCT04076761
• Lead Sponsor: Sunnybrook Health Sciences Centre

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-08-22
• Study First Submitted QC: 2019-08-30
• Study First Posted: 2019-09-03
• Study Start: 2019-12-11
• Primary Completion: 2022-09-30
• Study Completion: 2022-09-30
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-28
• Last Update Posted: 2022-12-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Trifluridine/Tipiracil	Trifluridine/Tipiracil	FTD/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.

Primary Outcome Measures

Name	Time	Method
Median progression-free survival (PFS)	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	As measured on the basis of RECIST v1.1 criteria

Secondary Outcome Measures

Name	Time	Method
Duration of response of FTD/TPI	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	As measured on the basis of RECIST v1.1 criteria
Quality of life: European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30	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)	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
Median overall survival of patients with cholangiocarcinoma treated with FTD/TPI.	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	As measured on the basis of RECIST v1.1 criteria
Safety and tolerability of FTD/TPI: CTCAE version 5.0	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)	Assessed by using CTCAE version 5.0 and tolerability
Disease Control Rate (Complete Response, Partial Response, Stable Disease) of FTD/TPI	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	As measured on the basis of RECIST v1.1 criteria

Trial Locations

Locations (1)

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada