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Intrahepatic CholangiocarcinomaPhase 2NCT04238637

Immunotherapy Combined With Y-90 SIRT Therapy in Advanced Stage Intrahepatic Biliary Tract Cancer (BTC)

A Phase 2 study testing Durvalumab and Tremelimumab in people with Intrahepatic Cholangiocarcinoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 8 sites in Germany.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

A multicenter Phase II, randomized, prospective, open-label Trial investigating the clinical impact on combining Specific Internal Radiotherapy (SIRT) with the PD1-L Inhibitor Durvalumab and the CTLA-4 Inhibitor Tremelimumab in patients with intrahepatic Biliary Tract Cancer Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Intrahepatic Cholangiocarcinoma
What is being tested?
Durvalumab and Tremelimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
8 sitesGermany
Study dates
1 Nov 2019to Dec 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Fully-informed written consent and locally required authorization (European Union [EU]: General Data Privacy Regulation (GDPR)) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
  • Age ≥ 18 years.
  • Histologically documented diagnosis of locally-advanced OR limited metasized intrahepatic BTC not amenable to curative treatment (tumor resection or ablation), specified as
  • Tumor being confined to the liver or
  • In case of presence of extrahepatic lesions, metastasis must be stable AND of limited extent* AND patient must have a potential benefit from study participation in comparison to standard of care systemic therapy per local tumor board evaluation.
  • Limited extent is defined in this protocol as presence of
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  • EITHER ≤3 malignant extrahepatic lymph nodes (short axis diameter ≥3cm)
  • OR metastatic lesions in one organ other than liver (if only single lesion is present diameter MUST be < 3cm; if up to 3 lesions in one organ each lesion MUST be ≤ 1cm).
  • Presence of peritoneal or brain metastatsis excludes patients from study participation (see exclusion criterion #4)
  • Tumor tissue (block or at least 4 slides) is available for translational research.
  • Patients with prior chemotherapy and/or immunotherapy can be enrolled if ONE of the following criteria is met:
  • Capecitabin or gemcitabine+cisplatin in the adjuvant setting
  • Experienced progressive disease under gemcitabine+cisplatin therapy in the advanced setting
  • Stable disease after 3 months of gemcitabine+cisplatin treatment
  • Experienced progressive disease under durvalumab+ gemcitabine+cisplatin in first line treatment
  • Experienced progressive disease under pembrolizumab+ gemcitabine+cisplatin in first line treatment
  • Has been considered candidate for standard-of-care Y-90 SIRT therapy per Investigator decision and after prior consultation with the tumor board if available at site and does not display contraindications against SIRT.
  • Contraindications against SIRT would be
  • hepatic tumor load > 50%
  • any Gastrointestinal deposition that cannot be corrected via angiographic techniques
  • irreversibly elevated serum bilirubin
  • renal insufficiency
  • increased pulmonary shunt fraction being able to deliver > 16.5 mCi to the lungs
  • gastrointestinal ulceration
  • hepatic dysfunction
  • biliary complications
  • portal hypertension
  • vascular injury and lymphopenia.
  • Performance status (PS) ≤ 1 (ECOG scale).
  • Body weight >30 kg
  • At least one measurable site of disease as defined by RECIST 1.1 criteria.
  • Adequate bone marrow and renal function
  • Adequate hepatic function (with stenting for any obstruction, if required)
  • Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
  • The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
  • Must have a life expectancy of at least 12 weeks.
  • If patient has concurrent Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection, meets the following criteria:
  • Patients with HBV or HCV infection should be monitored for viral levels during study participation.
  • Patients with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should have HBV DNA < 100 IU/ml and should be managed per local treatment guidelines.
  • Controlled (treated) hepatitis B subjects will be allowed if they started treatment at the time point of enrollment into the study by the latest and treatment is continued during study participation and for ≥ 6 months after end of study treatment.
  • HCV patients with advanced BTC are mostly not treated for their HCV infection. However, patients treated for HCV are considered suitable for inclusion if antiviral therapy has been completed ≥ 30 days prior to first administration of study drug.

Who cannot join

  • Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study.
  • Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment.
  • Prior immunotherapy or use of other investigational agents, including prior treatment with an anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T-lymphocyte associated antigen-4 (anti-CTLA-4) antibody, therapeutic cancer vaccines, apart from durvalumab and pembrolizumab as PD-L1 inhibitor in first line therapy.
  • Presence of peritoneal carcinomatosis or brain metastases.
  • Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
  • Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (eg, hormone replacement therapy) is acceptable.
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  • Prior radiotherapy treatment before the first dose of any study drug.
  • Major surgery (as defined by the Investigator) within 4 weeks prior to enrollment into the study; patients must have recovered from effects of any major surgery. Note: Local non-major surgery for palliative intent (e.g. surgery of isolated lesions, per-cutaneous biliary drainage or biliary stenting) is acceptable.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g. colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis].
  • Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, , serious active, uncontrolled, 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.
  • History of non-infectious pneumonitis requiring steroids, or patients with Grade ≥ 2 pneumonitis.
  • History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of IP and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
  • History of leptomeningeal carcinomatosis
  • Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have a CT/ MRI of the brain prior to study entry.
  • History of active primary immunodeficiency
  • History of allogenic organ transplantation.
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), or human immunodeficiency virus (positive HIV 1/2 antibodies) or active hepatitis B/hepatitis C co-infection.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 180 days after the last dose of durvalumab.
  • Known allergy or hypersensitivity to any of the IMPs or any of the constituents of the product.
  • Any co-existing medical condition that in the investigator's judgement will substantially increase the risk associated with the patient's participation in the study.
  • Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
  • Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].
  • Receipt of live attenuated vaccine within 30 days prior to the first administration of any of the IMPs and without need to receive any live attenuated vaccines during study conduct and for up to 30 days after end of Durvalumab treatment or 90 days after end of Tremelimumab treatment respectively.

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Germany8 sites

  • University Hospital Dresden

    Dresden

  • Clinic Essen Center

    Essen

  • University Hospital Essen

    Essen

  • University Hospital Halle

    Halle

  • Hannover Medical School

    Hanover

  • University Hospital Jena

    Jena

  • Munich Clinic Bogenhausen

    Munich

  • University Hospital Munich Grosshadern

    Munich

Other trials in Germany

About this study

Official title: Phase II Study of Immunotherapy With Durvalumab (MEDI4736) or Durvalumab and Tremelimumab, Both Combined With Y-90 SIRT Therapy in Advanced Stage Intrahepatic Biliary Tract Cancer (BTC)

A multicenter Phase II, randomized, prospective, open-label Trial investigating the clinical impact on combining Specific Internal Radiotherapy (SIRT) with the PD1-L Inhibitor Durvalumab and the CTLA-4 Inhibitor Tremelimumab in patients with intrahepatic Biliary Tract Cancer

Read the detailed description

IMMUWHY Phase II Clinical Trial will test the Addition of the immunotherapeutic agents Durvalumab and Tremelimumab after an initial Standard of Care SIRT in patients suffering from non-resectable intrahepatic Biliary Tract Cancer. Patients will be randomized into two experimental arms, one receiving Durvalumab only, the other one receiving Durvalumab + Tremelimumab. Clinical Outcomes will be compared vs. historical datasets.

Keywords
Intrahepatic Bile Duct Cancer, Intrahepatic Biliary Tract Carcinoma, Intrahepatic Cholangiocarcinoma, BTC, iBTC, iCCA
Medical subject headings
Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DurvalumabDrug

    Also called Other Name: MEDI4736

    Durvalumab IV (intravenous Infusion)

  • TremelimumabDrug

    Also called Study treatment

    Tremelimumab IV (intravenous Infusion)

Study groups in NCT04238637
Study groupRoleWhat they receive
Arm 1ExperimentalDurvalumab
Receives: Drug: Durvalumab
Arm 2ExperimentalDurvalumab in combination with Tremelimumab
Receives: Drug: Durvalumab; Drug: Tremelimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response rate (ORR) according to RECIST 1.1

    Proportion of allocated subjects with best response of complete or partial response

    Measured: 20 months

Secondary outcomes (4)

  1. Safety (rate of adverse events)

    Type, incidence and severity of AEs and SAEs graded according to NCI CTCAE v5.0

    Measured: From first patient included until study closure (approx. 43 months after First Patient Included)

  2. Duration of response (DoR)

    Time from that the measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that the PD is objectively documented or death

    Measured: From first measurement of CR or PR per RECIST 1.1 until disease progression occurs (up to 43 months until Study Closure)

  3. Progression free survival (PFS)

    Time from the date of randomization to the date of first observed disease progression (investigator assessment according to RECIST 1.1) or death from any cause

    Measured: From date of randomization until disease progression occurs (up to 43 months until Study Closure)

  4. Overall Survival (OS)

    time from the date of treatment allocation to the date of death.

    Measured: Date of enrollment until date of death if applicable (up to 43 months until Study Closure)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2020
  2. Study start1 Nov 2019
  3. Primary completionAug 2026 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

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
Randomised
Intervention model
Parallel groups
Model description
Two randomized Treatment arms
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04238637
Sponsor's protocol ID
IMMUWHY
Status last verified
Nov 2025
First submitted
19 Dec 2019
Last updated
5 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No IPD will be shared.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab and Tremelimumab in people with Intrahepatic Cholangiocarcinoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 8 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 42 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response rate (ORR) according to RECIST 1.1 (time frame: 20 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04238637.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2025.

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