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

  • STATUS
    Recruiting
  • End date
    Dec 6, 2025
  • participants needed
    50
  • sponsor
    Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Updated on 6 May 2022
renal function
cancer
serum bilirubin
hepatitis b surface antigen
kidney function tests
metastasis
progressive disease
hormone therapy
gemcitabine
durvalumab
biliary tract cancer

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

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.

Details
Condition Intrahepatic Cholangiocarcinoma
Treatment tremelimumab, durvalumab
Clinical Study IdentifierNCT04238637
SponsorInstitut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Last Modified on6 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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)
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 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
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

Exclusion Criteria

Presence of peritoneal carcinomatosis or brain metastases
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
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
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
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