Combining chemotherapy and Yttrium-90 treatment for liver cancer
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
This study is testing a new combination of chemotherapy and Yttrium-90 treatment to see if it can help people with liver cancer shrink their tumors and manage their disease better than standard treatments.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 16 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Inova Health Care Services Academic / other |
| Drugs / interventions | durvalumab, chemotherapy, prednisone |
| Locations | 1 site (Fairfax, Virginia) |
| Trial ID | NCT05422690 on ClinicalTrials.gov |
What this trial studies
This study aims to evaluate the effectiveness of a combination treatment involving gemcitabine, cisplatin, and Durvalumab chemotherapy alongside a direct tumor therapy called Yttrium-90 (Y-90) for patients with intrahepatic cholangiocarcinoma. The approach includes an induction phase with triplet chemotherapy, followed by concurrent Y-90 treatment, and a consolidation phase with doublet chemotherapy. The goal is to determine if this combined strategy can better shrink tumors and control cancer compared to standard treatments.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed unresectable intrahepatic cholangiocarcinoma who have not received prior systemic therapy within the last six months.
Not a fit: Patients with cirrhosis or those whose tumors are resectable may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a more effective option for patients with unresectable intrahepatic cholangiocarcinoma.
How similar studies have performed: While the combination of chemotherapy and Y-90 is a novel approach, similar studies have shown promise in treating other types of cancers.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Fairfax, Virginia
- Keary Janet — Fairfax, Virginia, United States (Recruiting)
Study contacts
- Principal investigator: Arthur A. Winer, MD — Inova Schar Cancer Institute
- Study coordinator: Keary Janet, BS
- Email: keary.janet@inova.org
- Phone: 571-472-0024
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.