Clinical trial NCT02456714: Second Line Chemotherapy FOLFIRINOX in Irresectable Cholangiocarcinoma
Official title: Second Line Chemotherapy FOLFIRINOX in Irresectable Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cholangiocarcinoma
Keywords: Cholangiocarcinoma
FOLFIRINOX
Phase II study
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2015-05-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Cholangiocarcinoma, is a malignant gastrointestinal tumor of low incidence with a poor prognosis. Chemotherapy is the most common treatment for advanced disease. On the basis of a phase III clinical study, cisplatin plus gemcitabine is considered standard first-line treatment in advanced cholangiocarcinoma patients, but there is no established second line therapy.

Since fluorouracil and leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) appears to be safe and demonstrated efficacy in clinical studies of advanced pancreatic cancer, colorectal cancer and a phase I study in cholangiocarcinoma, this combination could be an effective second-line treatment for patients with advanced cholangiocarcinoma.


Eligibility criteria: Inclusion Criteria:

* Histological or cytological diagnosis of cholangiocarcinoma.
* Metastatic disease or irresectable locally advanced cholangiocarcinoma.
* Measurable disease according RECIST criteria version 1.1.
* Age from 18 to 75 year.
* WHO/ECOG performance status 0-2.
* Patients who received at least 3 cycles of gemcitabine/cisplatin in the first line.
* Adequate hematological function (WBC \> 3.0 x 109/L, platelets \> 100 x109/L)
* Adequate hepatic function (bilirubin ≤ 1.5 x upper normal limit (ULN); ALAT or ASAT \<5x ULN in case of liver metastases and \< 2.5 x ULN in absence of liver metastases.
* Adequate renal function (creatinine clearance \> 60 ml/min; creatinine \<120 µmol/L)
* Absence of cardiac insufficiency, chest pain (not medically controlled) and myocardial infarction in the 12 months preceding study entry.
* Signed informed consent.

Exclusion Criteria:

* Concurrent secondary malignancies or other malignancies within 3 years prior to enter this study with the exception of non-metastatic basal cell or squamous cell skin cancer or carcinoma in situ of the cervix treated by cone-biopsy or resection
* Presence of cerebral or meningeal metastases
* Contraindication to any of the substances of the planned treatment.
* History of chronic diarrhea or colorectal inflammatory conditions, or of unresolved occlusion or sub-occlusion for which symptomatic treatment is being administered
* Active infection or other serious underlying conditions which may prevent the patient from receiving the planned treatment. For example: prolonged unresolved bacterial cholangitis with destruction of bile duct branches (e.g. after endoprosthesis insertion) or two or more cholangitis in the last 6 months. Patients with other active or uncontrolled severe infection, cirrhosis or chronic active hepatitis will be excluded.
* Presence of cardiac insufficiency, unstable angina pectoris, symptomatic congestive heart, failure myocardial infarction 6 months prior to randomization, serious uncontrolled cardiac arrhythmia.
* Inclusion in another investigational clinical trial
* Women who are pregnant, breast-feeding or not using adequate contraceptive
* Age younger than 18 or older than 76 years
* Individuals under correctional supervision or guardianship

Primary outcomes:
measure: pilot study: toxicity
timeFrame: 24 weeks
measure: phase II: the response rate
timeFrame: 24 weeks
Secondary outcomes:
measure: pilot study: the response rate
timeFrame: 24 weeks
measure: pilot study: time to progression.
timeFrame: 24 weeks
measure: pilot study: the overall survival
timeFrame: 24 weeks
measure: pilot study: quality of life
timeFrame: 24 weeks
measure: phase II: toxicity during the treatment period and 30 days after the treatment.
timeFrame: 24 weeks
measure: phase II: time to progression.
timeFrame: 24 weeks
measure: phase II: the overall survival.
timeFrame: 24 weeks
measure: phase II: quality of life
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic medical center Amsterdam
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: H.J. Klümpen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: J. Wilmink, MD, PhD
role: STUDY_CHAIR
References:
citation: Belkouz A, de Vos-Geelen J, Mathot RAA, Eskens FALM, van Gulik TM, van Oijen MGH, Punt CJA, Wilmink JW, Klumpen HJ. Efficacy and safety of FOLFIRINOX as salvage treatment in advanced biliary tract cancer: an open-label, single arm, phase 2 trial. Br J Cancer. 2020 Mar;122(5):634-639. doi: 10.1038/s41416-019-0698-9. Epub 2020 Jan 10.