The Purpose of This Research Study is to See if Combining Gemcitabine, Cisplatin and Durvalumab Chemotherapy Treatments With a Direct Tumor Therapy Yittrium-90 (Y-90) Will Work Better Together to Shrink Tumors and Control Cancer

July 7, 2025 updated by: Inova Health Care Services

A Phase II Single-center, Open-label, Single Arm Study of Induction Gemcitabine, Cisplatin and Durvalumab Followed by Gemcitabine, Cisplatin and Yttrium-90 (Y-90) Radioembolization for the Treatment of Locally Advanced Unresectable Intrahepatic Cholangiocarcinoma

The purpose of this research is to see if combining gemcitabine, cisplatin and Durvalumab chemotherapy treatments with a direct tumor therapy called Yittrium-90, will work better together to shrink the tumor and control cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult males and females at least 18 years of age
  • Histologically and/or cytologically confirmed iCCA that is previously untreated or, if systemic therapy has been rendered for prior disease, has been administered at least 6 months before the development of recurrent or de novo new sites of disease.
  • Unresectable disease, as deemed by the Inova multidisciplinary tumor board (i.e. disease that cannot be safely resected with negative margins, leaving 2 adjacent segments of liver with intact portal venous and hepatic arterial inflow and intact biliary and hepatic venous outflow with the future liver remnant of sufficient volume to avoid postoperative liver insufficiency)
  • Measurable disease per RECIST 1.1 at least 2 cm in size
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Noncirrhotic liver - patients should not have a preexisting diagnosis of cirrhosis either diagnosed via biopsy or with features consistent with cirrhosis on imaging (e.g. shrunken liver with nodularity consistent with cirrhosis). Child-Pugh score must be less than 5.
  • No evidence of extrahepatic disease, except for regional adenopathy that would be resected as part of a standard oncologic surgical procedure
  • Adequate organ function as indicated by the following laboratory values (Table 1)
  • Ability to complete testing in the protocol
  • Able and willing to consent to protocol

Exclusion Criteria:

  • Female patients who are pregnant or breast-feeding
  • History of allogeneic organ transplantation.

  • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:

    • Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
    • Patients with controlled type 1 diabetes on an insulin regimen are eligible for the study.
    • Patients with vitiligo or alopecia.
    • Any chronic skin condition that does not require systemic therapy.
    • Patients without an active autoimmune disease in the last 5 years may be included but only after consultation with the study physician.
    • Patients with diet controlled celiac disease.

  • Current or recent use of immunosuppressive medication within 14 days before durvalumab initiation except if:

    • Intranasal, inhaled, topical or local steroid injections
    • Systemic corticosteroids at physiologic doses that do not exceed 10 mg/day of prednisone or its equivalent.
    • Steroids as premedication for hypersensitivity reactions, (i.e. CT scan premedication).
  • Child-Pugh B7 or greater cirrhosis
  • Extrahepatic or perihilar cholangiocarcinoma
  • Gallbladder cancer
  • Pancreatic or ampullary cancer
  • Portal vein thrombosis involving the main portal vein or first order right or left portal vein branches
  • Extrahepatic disease, other than regional lymph nodes that would be removed at time of surgery as part of a routine oncologic procedure for iCCA
  • Previous treatment with chemotherapy, intra-arterial or radiotherapy for iCCA is exclusionary, with the exception of adjuvant therapy with capecitabine which is allowed.
  • Contraindication to durvalumab, gemcitabine, or cisplatin
  • Active hepatitis B or C for which patients refuse treatment. Patients who are newly diagnosed with active disease as part of protocol screening and are agreeable to initiate on antiviral treatment are allowed to enroll.
  • Contraindication found during work-up angiography, including significant lung shunting (lung dose >30 Gy for a single treatment or >50 Gy cumulative), or non-manageable extrahepatic deposition of technetium Tc 99m macroaggregated albumin on scintigraphy performed after planning angiography
  • > 75% hepatic tumor burden
  • Inability to protect non-target arteries to intestines or solid organs from radioembolization
  • Serum albumin < 3 g/dL
  • Serum bilirubin > 2 mg/dL, serum aspartate aminotransferase or alanine aminotransferase > 5 times upper limit of normal
  • Concomitant illness that would prevent adequate patient assessment or in the investigators' opinion pose an added risk for study participants.
  • Life-threatening intercurrent illness
  • Anticipated poor compliance
  • Prisoners or subjects who are involuntarily incarcerated
  • Persons with decisional incapacity/cognitive impairment
  • Any history or evidence of severe illness or any other condition that would make the patient, in the opinion of the investigator unsuitable for the study
  • Subject is enrolled in a separate interventional clinical trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: gemcitabine, cisplatin and Durvalumab chemotherapy with Yittrium-90
single arm - Induction Gemcitabine, Cisplatin and Durvalumab Triplet Chemotherapy followed by Gemcitabine, Cisplatin in combination with yttrium-90 (Y-90) Radioembolization
Drug: Induction Chemotherapy Triplet Therapy
Gemcitabine 1000 mg/m2, Cisplatin 25 mg/m2 infused on both day 1 and day 8 of a 21-day cycle. Durvalumab 1500 mg will be given on day 1 of each cycle.
Radiation: Concurrent Y-90 treatment
Patients will undergo a Y-90 treatment planning consultation by the treating interventional radiologist during cycle 1. One or two cycles (depending on tumor size) of cisplatin, 25 mg/m2 and gemcitabine 300 mg/m2 given on day 1 and day 8 in combination with Yttrium-90 (Y-90) microspheres which will be given on day 3-7 or day 10-21 at the discretion of the interventional radiologist, separated in time by at least 2 days from a chemo infusion during that cycle
Drug: Consolidation Doublet Therapy:
Gemcitabine 1000 mg/m2 and Cisplatin 25 mg/m2 given on days 1 and 8 of a 21-day cycle with durvalumab 1500 mg given on day 1 of each cycle for 3-5 additional cycles. For the cycle directly after Y-90, gemcitabine will be kept at a dose of 300 mg/m2 to minimize risk of toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessing the objective response rate (ORR) at 6 months in patients with locally advanced, unresectable intrahepatic cholangiocarcinoma (iCCA)
Time Frame: 6 months
Best response in terms of tumor shrinkage (by RECIST 1.1 criteria including complete + partial responses) obtained during protocol therapy.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessing Progression Free Survival (PFS)
Time Frame: 48 months
time from treatment initiation to disease progression, death or last patient contact
48 months
Hepatic Progression-Free Survival (HPFS)
Time Frame: 48 months
time from treatment initiation to hepatic disease progression, death or last patient contact
48 months
Overall Survival (OS)
Time Frame: 48 months
Time from treatment initiation to death due to any cause or last patient contact
48 months
Disease Control Rate (DCR)
Time Frame: 48 months
Complete Response + Partial Response + Stable Disease (by RECIST 1.1 and mRECIST criteria) obtained during protocol therapy.
48 months
R0 resection rate
Time Frame: 6 months
Rate of patients that achieve an R0 resection at 6 months.
6 months
treatment related impact on quality of life
Time Frame: 48 months
Self-assessed metric of treatment-related impact on Quality of Life (QOL) as measured by the Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) questionnaire with measures of Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, Hepatobiliary Cancer Subscale using a 5 point scale ((0) Not at all (1) A little bit; (2) Somewhat; (3) Quite a bit; (4) Very much). Better performance status, i.e. higher score, is associated with a higher quality of life.
48 months
safety and toxicity rate
Time Frame: 48 months
Development of Treatment Toxicities (grade 3 non-hematologic toxicities persisting beyond 2 weeks despite best supportive care, any grade 3 hematologic toxicities, or any toxicity grade 4 or higher) assessed as per NCI's CTCAE v5.0 criteria.
48 months
rate of downstaging to surgery
Time Frame: 6 months
Rate of downstaging to surgery that occurs during protocol therapy at 6 months.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inova Health Care Services

Investigators

  • Principal Investigator: Arthur A. Winer, MD, Inova Schar Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 12, 2024

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2028

Study Registration Dates

First Submitted

May 27, 2022

First Submitted That Met QC Criteria

June 14, 2022

First Posted (Actual)

June 16, 2022

Study Record Updates

Last Update Posted (Actual)

July 10, 2025

Last Update Submitted That Met QC Criteria

July 7, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • U22-02-4670

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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