Extrahepatic CholangiocarcinomaPhase 2/3NEODISCONCT06923475
Neoadjuvant Gemcitabine and Cisplatin in Combination With Perioperative Pembrolizumab Versus Upfront Surgery for Patients With Primary Resectable and Borderline Resectable Perihilar and Distal Cholangiocarcinoma
A Phase 2/3 study testing Pembrolizumab and Gemcitabine, Cisplatin in people with Extrahepatic Cholangiocarcinoma and Perihilar Cholangiocarcinoma, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
Extrahepatic cholangiocarcinoma (eCCA) is a rare and aggressive cancer with poor prognosis. ECCA can be further subcategorised in perihilar and distal cholangiocarcinoma (pCCA and dCCA). Surgical resection is the only potential cure, but only one-third of patients are eligible. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extrahepatic Cholangiocarcinoma, Perihilar Cholangiocarcinoma, Distal Cholangiocarcinoma
- What is being tested?
- Pembrolizumab and Gemcitabine, Cisplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteNetherlands
- Study dates
- 17 Apr 2026to 6 Nov 2028
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed resectable or borderline resectable pCCA and dCCA. These are all the patients considered candidates for upfront surgical exploration, with intent to resect, as confirmed by local MDT and the study expert panel also taking into consideration endoscopic and radiological findings. In cases where drainage is not required, patients with a disease highly suspicious for extrahepatic cholangiocarcinoma, as determined by the expert MDT, may be included without histological proof to prevent unnecessary post-ERCP complications.
- Successful drainage, in case of clinical significant bile duct obstruction.
- MidCCA inclusion in the NEODISCO-trial will be permitted and will be included according to the proposed type of resection.
- Male/female participants who are at least 18 years of age on the day of signing informed consent.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
Who cannot join
- Upfront "clearly" unresectable pCCA: circumferential unreconstructable vascular involvement of the FLR and/or insufficient FLR for potential radical resection. Insufficient FLR is defined as <30% residual volume or a function <2.7 min/m2. Patients considered borderline resectable but, by the discretion of the MDT, not a candidate for upfront exploration/resection, are considered ineligible for NEODISCO.
- Upfront clearly unresectable dCCA (following DPCG criteria).
- Patients with proven N2 lymph nodes (according to the AJCC 8th edition).
- PCCA eligible for liver transplantation.
- Intrahepatic cholangiocarcinoma with hilar involvement.
- Cancer suspicious for ampullary carcinoma (for instance involvement of papilla during endoscopy).
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- Local recurrence following prior resection of eCCA (patients who develop local recurrence during the study are however not excluded).
- Patients with underlying liver diseases: PSC, untreated hepatitis, cirrhosis child-Pugh B, C.
- Previous malignancy unless no evidence of disease, or diagnosed more than 3 years before diagnosis of eCCA, or with a life expectancy of more than 5 years from date of inclusion.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam University Medical Center
Amsterdam
Emma van der Meulen, MD, +31-20-4444321, e.e.vandermeulen@amsterdamumc.nl
Britte ten Haaft, b.tenhaaft@amsterdamumc.nl
About this study
Official title: Neoadjuvant Gemcitabine and Cisplatin in Combination With Perioperative Pembrolizumab Versus Upfront Surgery for Patients With Primary Resectable and Borderline Resectable Perihilar and Distal Cholangiocarcinoma (NEODISCO): A Multicentre Phase 2B/3 Randomized Controlled Trial
Extrahepatic cholangiocarcinoma (eCCA) is a rare and aggressive cancer with poor prognosis. ECCA can be further subcategorised in perihilar and distal cholangiocarcinoma (pCCA and dCCA). Surgical resection is the only potential cure, but only one-third of patients are eligible. Even among those deemed resectable, a significant portion (≈30%) experience disease progression before surgery, while another 30% are found unresectable during exploration. High recurrence rates and postoperative complications further limit survival, with 5-year overall survival ranging from 13% (R1 resection) to 40% (R0 resection). Given the long preoperative work-up period and lack of treatment during this phase, a neoadjuvant approach may improve outcomes by increasing R0 resections, reducing recurrence, and optimizing patient selection.
This multicenter, randomized phase 2B/3 trial aims to assess whether neoadjuvant gemcitabine and cisplatin plus perioperative pembrolizumab improves event-free survival in patients with resectable and borderline resectable pCCA and dCCA.
- Conditions
- Extrahepatic Cholangiocarcinoma, Perihilar Cholangiocarcinoma, Distal Cholangiocarcinoma, Resectable, Borderline Resectable
- Being tested
- Pembrolizumab, Gemcitabine, Cisplatin
- Keywords
- Extrahepatic cholangiocarcinoma, Perihilar Cholangiocarcinoma, Distal Cholangiocarcinoma, Resectable, Borderline resectable
- Medical subject headings
- Cholangiocarcinoma, Klatskin Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Patients will initiate with 2 sets of 3 cycles of neoadjuvant gemcitabine and cisplatin in combination with perioperative pembrolizumab (up to total of 1 year immunotherapy treatment)
Gemcitabine, CisplatinDrug
Patients will initiate with 2 sets of 3 cycles of neoadjuvant gemcitabine and cisplatin in combination with perioperative pembrolizumab (up to total of 1 year immunotherapy treatment)
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Neoadjuvant gemcitabine plus cisplatin in combination with perioperative pembrolizumab (Intervention) Receives: Drug: Pembrolizumab; Drug: Gemcitabine, Cisplatin |
| Arm B | No intervention | Upfront surgery (Standard of care) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event Free Survival
An event is defined as the time from randomization to any progression of disease leading to unresectability, progression or recurrence of disease after surgery (all based on RECIST or pathology) or death from any cause.
Measured: 18 months
Secondary outcomes (1)
Overall Survival (OS)
Most important secondary endpoint: median OS defined as the time from randomization to death due to any cause. 2-, 3- and 5-years OS will also be reported.
Measured: Median, 2-, 3-, 5- years OS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2025
- Study start17 Apr 2026
- Primary completion6 Nov 2028 (estimated)
- Study completion6 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Extrahepatic CholangiocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University Medical Center, UMC Utrecht, University Medical Center Groningen, Erasmus Medical Center
- Responsible party
- Principal investigator, Trial Office Medical Oncology VUmc, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06923475
- Sponsor's protocol ID
- 2024-516898-72-00
- Other IDs
- R-000724
- Acronym
- NEODISCO
- Status last verified
- Aug 2026
- First submitted
- 25 Feb 2025
- Last updated
- 25 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes