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

NCT05422690 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: U22-02-4670
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Assessing the objective response rate (ORR) at 6 months in patients with locally advanced, unresectable intrahepatic cholangiocarcinoma (iCCA)

  Best response in terms of tumor shrinkage (by RECIST 1.1 criteria including complete + partial responses) obtained during protocol therapy.

  6 months

Secondary Outcomes (8)

• Assessing Progression Free Survival (PFS)

  48 months

• Hepatic Progression-Free Survival (HPFS)

  48 months

• Overall Survival (OS)

  48 months

• Disease Control Rate (DCR)

  48 months

• R0 resection rate

  6 months

Study Arms (1)

gemcitabine, cisplatin and Durvalumab chemotherapy with Yittrium-90

EXPERIMENTAL

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; Radiation: Concurrent Y-90 treatment; Drug: Consolidation Doublet Therapy:

Interventions

Induction Chemotherapy Triplet Therapy DRUG

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.

gemcitabine, cisplatin and Durvalumab chemotherapy with Yittrium-90

Concurrent Y-90 treatment RADIATION

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

gemcitabine, cisplatin and Durvalumab chemotherapy with Yittrium-90

Consolidation Doublet Therapy: DRUG

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.

gemcitabine, cisplatin and Durvalumab chemotherapy with Yittrium-90

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Inova Health Care Services: lead

Study Sites (1)

Keary Janet

Fairfax, Virginia, 22031, United States

RECRUITING

Related Publications (25)

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• Yeh CN, Hsieh FJ, Chiang KC, Chen JS, Yeh TS, Jan YY, Chen MF. Clinical effect of a positive surgical margin after hepatectomy on survival of patients with intrahepatic cholangiocarcinoma. Drug Des Devel Ther. 2014 Dec 17;9:163-74. doi: 10.2147/DDDT.S74940. eCollection 2015.

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• Lang H, Sotiropoulos GC, Fruhauf NR, Domland M, Paul A, Kind EM, Malago M, Broelsch CE. Extended hepatectomy for intrahepatic cholangiocellular carcinoma (ICC): when is it worthwhile? Single center experience with 27 resections in 50 patients over a 5-year period. Ann Surg. 2005 Jan;241(1):134-43. doi: 10.1097/01.sla.0000149426.08580.a1.

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• Ilyas SI, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma - evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018 Feb;15(2):95-111. doi: 10.1038/nrclinonc.2017.157. Epub 2017 Oct 10.

  PMID: 28994423 RESULT

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MeSH Terms

Conditions

Cholangiocarcinoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Arthur A. Winer, MD

  Inova Schar Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Keary Janet, BS

CONTACT

571-472-0024; keary.janet@inova.org

Elahe Mollapour

CONTACT

elahe.mollapour@inova.org

Study Design

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

Model Details: Treatments are repeated every 21 days. Chemotherapy will be administered on days 1 and 8 of the 21 day cycle. For the first two cycles, treatment will consist of three drugs, gemcitabine, cisplatin and Durvalumab. After these two cycles, the Durvalumab will be removed from the treatment plan and participants will continue on trial with gemcitabine and cisplatin alone for 6 additional cycles (8 total cycles, or 6 months total of treatment). During the 3rd and possibly the 4th cycle, these drugs will be given at a reduced dose as y-90 treatment to the tumors in your liver will also be given. The interventional team will administer y-90 during these cycles as either one dose during cycle 3, or two doses, one during cycle 3 and one during cycle 4 if there is too much cancer to treat all at once. The remaining cycles of treatment will be with gemcitabine and cisplatin by themselves.

Study Record Dates

• First Submitted: May 27, 2022
• First Posted: June 16, 2022
• Study Start: June 12, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2028
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)