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

NCT04238637 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: IMMUWHY
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 8

Brief 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

Conditions

Intrahepatic Cholangiocarcinoma

Keywords

Intrahepatic Bile Duct Cancer; Intrahepatic Biliary Tract Carcinoma; Intrahepatic Cholangiocarcinoma; BTC; iBTC; iCCA

Outcome Measures

Primary Outcomes (1)

• Objective Response rate (ORR) according to RECIST 1.1

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

  20 months

Secondary Outcomes (4)

• Safety (rate of adverse events)

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

• Duration of response (DoR)

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

• Progression free survival (PFS)

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

• Overall Survival (OS)

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

Other Outcomes (1)

• Translational research

  3 months

Study Arms (2)

Arm 1

EXPERIMENTAL

Durvalumab

Drug: Durvalumab

Arm 2

EXPERIMENTAL

Durvalumab in combination with Tremelimumab

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

Durvalumab IV (intravenous Infusion)

Also known as: Other Name: MEDI4736

Arm 1; Arm 2

Tremelimumab DRUG

Tremelimumab IV (intravenous Infusion)

Also known as: Study treatment

Arm 2

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).
• 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

You may not qualify if:

• 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 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.
• 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

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• AstraZeneca: collaborator

Study Sites (8)

University Hospital Dresden

Dresden, Germany

Location

Clinic Essen Center

Essen, Germany

Location

University Hospital Essen

Essen, Germany

Location

University Hospital Halle

Halle, Germany

Location

Hannover Medical School

Hanover, Germany

Location

University Hospital Jena

Jena, Germany

Location

Munich Clinic Bogenhausen

Munich, Germany

Location

University Hospital Munich Grosshadern

Munich, Germany

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

durvalumab; tremelimumab; Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

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

Study Officials

• Salah-Eddin Al-Batran, Professor

  IKF Klinische Krebsforschung GmbH

  STUDY DIRECTOR

Study Design

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

Model Details: Two randomized Treatment arms

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: January 23, 2020
• Study Start: November 1, 2019
• Primary Completion: August 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8)