Extrahepatic CholangiocarcinomaPhase 2NCT06440993
Durvalumab + Intraductal Radiofrequency Ablation (ID-RFA) in Extra- and Intrahepatic Cholangiocarcinoma
A Phase 2 study testing Gemcitabine, Cisplatin and Durvalumab in people with Extrahepatic Cholangiocarcinoma and Unresectable Perihilar or Ductal CCA, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 12 sites in Germany.
Trial 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 or intrahepatic CCA with indication for bile duct stenting and palliative systemic therapy as determined by the local multidisciplinary team (MDT)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extrahepatic Cholangiocarcinoma, Unresectable Perihilar or Ductal CCA
- What is being tested?
- Gemcitabine, Cisplatin and Durvalumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 12 sitesGermany
- Study dates
- 23 Aug 2024to Apr 2028
- Phase
- Phase 2
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
- 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 extrahepatic cholangiocarcinoma or intrahepatic CCA with perihilar stricture according to Bismuth-Corlette classification 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
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- Patient tolerated RFA prior to inclusion and is eligible for repeat RFA during the study (does not have any contraindications) as determined by investigator.
- 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)
- Albumin levels ≥ 2.8 g/dL
- Patients not receiving therapeutic anticoagulation must have an INR< 2.0 ULN and PTT < 1.5 ULN within 7 days prior to randomization. The use of full dose anticoagulants is allowed as long as the INR or PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least three weeks at the time of inclusion
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN unless liver metastases are present, in which case it must be ≤ 5x ULN
- Serum Creatinine ≤ 1.5 x ULN and a calculated creatinine clearance rate ≥ 60 mL /min
- Female patients defined as women of childbearing potential (WOCBP) or male patients with WOCBP partners must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 6 months after the last dose of chemotherapy or for at least 3 months after last dose of durvalumab, whatever happens last. Male patients must refrain from donating sperm during this same period. Male patients with a pregnant partner must agree to remain abstinent or to use a condom for the duration of the pregnancy.
Who cannot join
- 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.
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- Patient has any unresolved NCI CTCAE grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and laboratory values defined in the inclusion criteria
- 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
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
Germany12 sites, 12 recruiting
- Recruiting
Uniklinik RWTH Aachen
Aachen
Cennet Sahin, Dr.
- Recruiting
Universitätsklinikum Bonn
Bonn
Maria Gonzales-Carmona, Prof. Dr.
- Recruiting
Kliniken Köln
Cologne
Bernhard Sibbing, Dr.
- Recruiting
Universitätsklinikum Köln
Cologne
Dirk Waldschmidt, Dr.
- Recruiting
Evangelisches Krankenhaus Düsseldorf
Düsseldorf
Torsten Benya, PD Dr.
- Recruiting
Universitätsklinikum Düsseldorf
Düsseldorf
Christoph Roderburg, Prof. Dr.
- Recruiting
Krankenhaus Nordwest
Frankfurt, 60488
Thorsten O Goetze, Prof. Dr., goetze.thorsten@khnw.de
- Recruiting
Universitätsmedizin Göttingen
Göttingen
Johanna Reinecke, Dr.
- Recruiting
Medizinische Hochschule Hannover
Hanover
Anna Saborowski, PD Dr.
- Recruiting
UKSH Campus Lübeck
Lübeck
Jens Marquardt, Prof. Dr.
- Recruiting
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz
Friedrich Foerster, PD Dr.
- Recruiting
Universitätsklinik Münster
Münster
Jonel Trebicka, Prof. Dr. Dr.
About this study
Official title: The CLEAN-DUCT / TRITICC-3 Trial - Phase IIa, Prospective, Single Arm, Open Label, Non-randomized, Multi-center Pilot Study of Durvalumab (MEDI4736) + Intraductal Radiofrequency Ablation (ID-RFA) in Extra- and Intrahepatic Cholangiocarcinoma
The present clinical trial is a prospective, investigator-initiated, single-arm, open-label, multicenter phase II trial. Patients with unresectable perihilar and/or ductal or intrahepatic 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 extra- and intrahepatic cholangiocarcinoma, the use of a combination radiofrequency ablation followed by systemic treatment with chemotherapy plus durvalumab might further increase the anti-tumor activity.
- Being tested
- Gemcitabine, Cisplatin, Durvalumab, ID-RFA
- Medical subject headings
- Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Gemcitabine, 1,000 mg/m2 IV
CisplatinDrug
Cisplatin, 25 mg/m2 IV
DurvalumabDrug
Durvalumab, 1,500 mg IV
ID-RFAProcedure or surgery
endoscopic intraductal RFA
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Gemcitabine; Drug: Cisplatin; Drug: Durvalumab; Procedure: ID-RFA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival rate
Overall survival rate after 12 months (OS@12months) defined as proportion of patients alive 12 months after enrollment
Measured: at 12 months
Secondary outcomes (6)
Progression-free survival (PFS)
Progression-free survival (PFS) defined as time from enrollment to the date of disease progression or death from any cause
Measured: at study end
Overall survival (OS)
Overall survival (OS) Defined as time from enrollment to the date of death from any cause
Measured: at study end
Incidence and nature of adverse events using NCI CTCAE 5.0
Assessment of safety of the treatment as determined by the incidence, nature, causality, frequency, timing and severity of adverse events using NCI CTCAE 5.0
Measured: through study completion, up to 3years
Time to cholangitis
Time to cholangitis Defined as time from enrollment to the date of confirmed cholangitis
Measured: from enrollment to first cholangitis event, up to 3 years
To assess quality of life (QoL) data from patients using EORTC QLQ-BIL21
To assess quality of life (QoL) data from patients using EORTC QLQ-BIL21
Measured: through study completion, up to 3years
To assess quality of life (QoL) data from patients using EORTC QLQ-C30
To assess quality of life (QoL) data from patients using EORTC QLQ-C30
Measured: through study completion, up to 3years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2024
- Study start23 Aug 2024
- Primary completionJan 2027 (estimated)
- Study completionApr 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
- Sponsor type
- University, hospital or other
- Collaborators
- Universitätsklinikum Düsseldorf, Germany, Universitätsklinikum Köln, AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Salah-Eddin SE Al-Batran, Prof. Dr., Study chair, Frankfurter Institut fuer Klinische Krebsforschung IKF GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06440993
- Sponsor's protocol ID
- CLEAN-DUCT / TRITICC-3
- Other IDs
- ESR-23-22156, 2023-509165-21-00, IKF-t070, 2023
- Status last verified
- Oct 2026
- First submitted
- 29 May 2024
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No