Second Line Chemotherapy FOLFIRINOX in Irresectable Cholangiocarcinoma (4CC)

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.

Study Overview

• Status: Completed
• Conditions: Cholangiocarcinoma
• Intervention / Treatment: Drug: FOLFIRINOX

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105AZ
    • Academic Medical Center Amsterdam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Progressive cholangiocarcinoma, second line treatment; FOLFIRINOX	Drug: FOLFIRINOX; Other Names: Second line treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pilot study: toxicity	number of adverse events in accordance with CTCAEv4.0	24 weeks
phase II: the response rate		24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pilot study: the response rate		24 weeks
pilot study: time to progression.		24 weeks
pilot study: the overall survival		24 weeks
pilot study: quality of life		24 weeks
phase II: toxicity during the treatment period and 30 days after the treatment.	number of adverse events in accordance with CTCAEv4.0	24 weeks
phase II: time to progression.		24 weeks
phase II: the overall survival.		24 weeks
phase II: quality of life		24 weeks

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: H.J. Klümpen, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Study Chair: J. Wilmink, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

General Publications

• 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.

Helpful Links

• Final publication

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2016
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: March 10, 2015
• First Submitted That Met QC Criteria: May 27, 2015
• First Posted (Estimate): May 28, 2015

Study Record Updates

• Last Update Posted (Actual): March 10, 2020
• Last Update Submitted That Met QC Criteria: March 6, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Phase II study; Cholangiocarcinoma; FOLFIRINOX
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Antineoplastic Agents; Folfirinox
• Other Study ID Numbers: volgt