Durvalumab + Intraductal Radiofrequency Ablation (ID-RFA) in Extrahepatic Cholangiocarcinoma

NCT06440993 | Recruiting Phase 2

• 4 other identifiers: CLEAN-DUCT / TRITICC-32023-509165-21-00ESR-23-22156IKF-t070
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 10

Brief Summary

The present clinical trial is a prospective, investigator-initiated, single-arm, open-label, multicenter phase II trial. Patients with unresectable perihilar and/or ductal CCA with indication for bile duct stenting and palliative systemic therapy as determined by the local multidisciplinary team (MDT), who already resolved cholestasis due to RFA + Stent will be enrolled. We hypothesize that in patients with extrahepatic cholangiocarcinoma, the use of a combination radiofrequency ablation followed by systemic treatment with chemotherapy plus durvalumab might further increase the anti-tumor activity.

Conditions

Extrahepatic Cholangiocarcinoma; Unresectable Perihilar or Ductal CCA

Outcome Measures

Primary Outcomes (1)

• Overall survival rate

  Overall survival rate after 12 months (OS@12months) defined as proportion of patients alive 12 months after enrollment

  at 12 months

Secondary Outcomes (6)

• Progression-free survival (PFS)

  at study end

• Overall survival (OS)

  at study end

• Incidence and nature of adverse events using NCI CTCAE 5.0

  through study completion, up to 3years

• Time to cholangitis

  from enrollment to first cholangitis event, up to 3 years

• To assess quality of life (QoL) data from patients using EORTC QLQ-BIL21

  through study completion, up to 3years

Study Arms (1)

systemic plus ID-RFA

EXPERIMENTAL

systemic treatment: - combination treatment for 8 cycles (Q3W): * Gemcitabine, 1,000 mg/m2 IV, on day 1 and 8, * Cisplatin, 25 mg/m2 IV, on day 1 and 8 * Durvalumab, 1,500 mg IV, on day 1 followed by * Durvalumab maintenance, 1,500 mg IV, PLUS • 2 endoscopic intraductal RFA

Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab; Procedure: ID-RFA

Interventions

Gemcitabine DRUG

Gemcitabine, 1,000 mg/m2 IV

systemic plus ID-RFA

Cisplatin DRUG

Cisplatin, 25 mg/m2 IV

systemic plus ID-RFA

Durvalumab DRUG

Durvalumab, 1,500 mg IV

systemic plus ID-RFA

ID-RFA PROCEDURE

endoscopic intraductal RFA

systemic plus ID-RFA

Eligibility Criteria

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

You may qualify if:

• Patient\* has given written informed consent.
• Patient is ≥ 18 years of age at time of signing the written informed consent.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Patient has been diagnosed with histologically or cytologically confirmed
• histologically or cytologically confirmed cholangiocarcinoma as adenocarcinoma of pancreatobiliary type
• unresectable perihilar and/or ductal cholangiocarcinoma with indication for bile duct stenting and palliative systemic therapy as determined by the local multidisciplinary team (MDT) and already resolved cholestasis due to RFA + stent
• Patient is eligible for palliative systemic therapy based on clinical and laboratory parameters (except hyperbilirubinemia) as determined by the local MDT
• Patient has a ECOG ≤ 1.
• Patient has life expectancy of ≥ 12 weeks
• Patient has body weight \> 30 kg
• Adequate blood count, liver-enzymes, and renal function:
• ANC \> 1,500 cells/μL without the use of hematopoietic growth factors
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Hemoglobin ≥ 9 g/dL
• Serum total bilirubin ≤ 3x 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 INR values)

You may not qualify if:

• Patient received previous or simultaneous endobiliary treatment other than RFA (e.g. PDT or brachytherapy)
• Patient received previous systemic therapy with a PD-1, PD-L1 inhibitor (including durvalumab) or CTLA4 inhibitor or classical chemotherapy agents like platinum, fluoropyrimidine or gemcitabine-based regimens.
• Patient receives any concurrent chemotherapy, investigational product or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replace therapy) is acceptable.
• Patient has known hypersensitivity to any component of the durvalumab formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein and/or any known contraindication (including hypersensitivity) to gemcitabine or cisplatin.
• Patient has history of primary immunodeficiency
• Patient has stage B cirrhosis according to Child-Pugh criteria (or worse) or cirrhosis (of any grade) with a history of hepatic encephalopathy or clinically significant ascites resulting from cirrhosis. Clinically significant ascites is defined as ascites resulting from cirrhosis requiring diuretics or paracentesis.
• Patients with grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the Lead Investigator
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Lead Investigator.
• Patient had a prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• Patient has active or history of autoimmune or inflammatory disorders (including, but not limited to, inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis\]) . The following are exceptions:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement
• Patients with any chronic skin condition that does not require systemic therapy
• Patients with celiac disease controlled by diet alone
• Patients without active disease in the last 5 years may be included but only after consultation with the Lead Investigator

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Universitätsklinikum Düsseldorf, Germany: collaborator
• Universitätsklinikum Köln: collaborator
• AstraZeneca: collaborator

Study Sites (10)

Uniklinik RWTH Aachen

Aachen, Germany

RECRUITING

Universitätsklinikum Bonn

Bonn, Germany

RECRUITING

Universitätsklinikum Köln

Cologne, Germany

RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, Germany

RECRUITING

Krankenhaus Nordwest

Frankfurt, 60488, Germany

RECRUITING

Universitätsmedizin Göttingen

Göttingen, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, Germany

RECRUITING

UKSH Campus Lübeck

Lübeck, Germany

RECRUITING

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, Germany

RECRUITING

Universitätsklinik Münster

Münster, Germany

NOT YET RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Gemcitabine; Cisplatin; durvalumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Salah-Eddin SE Al-Batran, Prof. Dr.

  Frankfurter Institut fuer Klinische Krebsforschung IKF GmbH

  STUDY CHAIR

Central Study Contacts

Christoph Roderburg, Prof. Dr.

CONTACT

+49 211 8108030; christoph.roderburg@med.uni-duesseldorf.de

Johanna Riedel, Dr.

CONTACT

+49 69 5899 787; clean-duct@ikf-khnw.de

Study Design

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

Study Record Dates

• First Submitted: May 29, 2024
• First Posted: June 4, 2024
• Study Start: August 23, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (10)