Efficacy and Safety of Trifluridine/Tipiracil in Combination With Irinotecan as a Second Line Therapy in Patients With Cholangiocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Cholangiocarcinoma
- Sponsor
- Heinrich-Heine University, Duesseldorf
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Median progression free survival (PFS)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Detailed Description
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. Patients will be treated until radiological progression. In average this will be about 4 months. A follow up is planned every 3 months up to 6 months to asses life quality and progression data.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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):
Exclusion Criteria
- •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
Outcomes
Primary Outcomes
Median progression free survival (PFS)
Time Frame: through study completion, an average of 1 year (~4 months intervention + 6 months Follow Up)
Median progression free survival (PFS)
Secondary Outcomes
- 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 - EuroQol-5Dimensions-3Levels (EQ-5D-5L) questionnaires(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))