Trifluridine/Tipiracil in Combination With Irinotecan as a Second Line Therapy in Patients With Cholangiocarcinoma

NCT04059562 | Completed Phase 2

• 1 other identifier: 17-157
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single arm, open label, non-randomized, exploratory, multi-centre pilot study with median progression free survival as primary outcome. In total 28 patients (including 3 calculated drop outs and invalid cases) with advanced cholangiocellular carcinoma after failure of a gemcitabine based first-line therapy will be enrolled at 5 centres. To examine the efficacy of a combination therapy of Trifluridine/Tipiracil and Irinotecan in patients with advanced, non resectable or metastatic cholangio- and gallbladder carcinoma after failure to respond to a previous gemcitabine treatment. The study will be accompanied by a translational research program: Before treatment and after each radiological tumor assessment (Q6W) blood and stool will be collected and extensive panels of biomarkers will be accessed.

Conditions

Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Median progression free survival (PFS)

  Median progression free survival (PFS)

  through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)

Secondary Outcomes (6)

• Progression-free survival rate

  At 4 months

• Median overall survival

  through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)

• Response according to RECIST 1.1

  through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)

• Safety (type, grade and frequency of Adverse Events (AEs)/Serious Adverse Events (SAEs))

  through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)

• Quality of life - European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-30)

  through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)

Study Arms (1)

Treatment

EXPERIMENTAL

Combination of Lonsurf® and Irinotecan

Combination Product: Combination of Lonsurf® and Irinotecan

Interventions

Combination of Lonsurf® and Irinotecan COMBINATION_PRODUCT

Trifluridine/Tipiracil (Lonsurf®) and Irinotecan * Trifluridine/Tipiracil will be administered at a dose of 25 mg/m2 / dose twice daily on days 1-5 followed by a 9-days recovery period from day 6 trough day 14 of each 14-days treatment cycle. * Irinotecan will be administered at the same time as Trifluridine/Tipiracil (Lonsurf®) on day 1 of each cycle at a dose of 180 mg/m2 / dose.

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent incl. participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) prior to performing any protocol-related procedures, including screening evaluations
• Age ≥ 18 years at time of study entry
• Histologically or cytologically confirmed, non-resectable, locally advanced or metastatic cholangiocarcinoma or gall bladder carcinoma
• Measurable or assessable disease according to RECIST 1.1
• Documented disease progression after prior gemcitabine or gemcitabine containing therapy. Examples of permitted therapies include, but are not limited to: a) Single agent gemcitabine); b) Any gemcitabine-based regimen, with or without maintenance gemcitabine
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Ability to take medications orally
• Adequate blood count, liver-enzymes, and renal function:
• Absolute neutrophil count (ANC) \> 1,500 cells/μL without the use of hematopoietic growth factors; and Platelet count ≥ 100 x 109/L (\>100,000 per mm3) and Hemoglobin \> 9 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 9 g/dL)
• Serum total bilirubin ≤ 1.5x upper normal limit (ULN) (biliary drainage is allowed for biliary obstruction; elevated bilirubin should be caused by obstruction not impaired liver function as assessed by albumin and international normalised ratio (INR) values):
• Albumin levels ≥ 3.0 g/dL
• aspartate aminotransferase (AST) (SGOT) and Alanine transaminase (ALT) (SGPT) ≤ 5 x institutional upper limit of normal
• Serum Creatinine ≤ 1.5 x ULN and a calculated glomerular filtration rate ≥ 30 mL per minute Adequate renal and bone marrow function
• In case of liver cirrhosis: Child-Pugh A
• Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control

You may not qualify if:

• Age \< 18 years
• Central nerve system (CNS) metastases
• Active, uncontrolled infection
• Additional malignancy within the past 2 years (except adequately treated in-situ carcinoma of the cervix or non-melanoma skin cancer)
• Clinically significant gastrointestinal disorders including bleeding, inflammation, occlusion, or diarrhea \> grade 1
• Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
• Known hypersensitivity to Trifluridine/Tipiracil or Camptothecin (CPT)-11 or their components
• Medication that is known to interfere with any of the agents applied in the trial
• Pregnancy or lactating female
• Prior partial or total gastrectomy
• Patients who might be dependent on the sponsor, site or the investigator
• Patients who have been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
• Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts \[§ 40 Abs. 1 S. 3 Nr. 3a German drug law (AMG)\].

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead
• Servier: collaborator

Study Sites (1)

Klinik für Gastroenterologie, Hepatologie und Infektiologie

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Related Publications (29)

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MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Irinotecan

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Christoph Roderburg, Prof.

  Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Combination of Lonsurf® and Irinotecan in 28 patients with cholangiocarcinoma.

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: August 16, 2019
• Study Start: October 28, 2021
• Primary Completion: January 8, 2024
• Study Completion: January 8, 2024
• Last Updated: March 27, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)