90Y Transarterial Radioembolization (TARE) Plus Gemcitabine and Cisplatin in Unresectable Intrahepatic Cholangiocarcinoma

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and maximum tolerated dose (MTD) of 90 Y TARE (Y90) in combination with gemcitabine and cisplatin in patients with unresectable intrahepatic cholangiocarcinoma (ICC).

Official Title
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A Traditional Feasibility Study of Gemcitabine, Cisplatin, and 90Y TARE for Unresectable Intrahepatic Cholangiocarcinoma

Conditions
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Intrahepatic Cholangiocarcinoma

Intervention / Treatment
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* Device: SIR-Spheres microspheres (Yttrium-90 Microspheres)
* Drug: Gemcitabine
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic Documentation: Core needle biopsy or surgical specimen that confirms intrahepatic cholangiocarcinoma (ICC). Patients must be determined to be unresectable by a multidisciplinary team that includes a hepatobiliary surgeon. No prior liver radiation therapy or immunotherapy for cholangiocarcinoma. Only one previous single agent chemotherapy for ICC allowed. Patient may have prior liver resection. Age > 18 years of age. Eastern Cooperative Oncology Group (ECOG) performance status < 2 (see Appendix E) Child's Pugh score of A (see Appendix F) Life expectancy of greater than 4 months Normal organ and marrow function as outlined in the protocol. Willingness to use effective contraceptive methods during the study. Patient may participate in the female (or female partner of male subject), either is not of childbearing potential (defined as postmenopausal for > 1 year or surgically sterile) or is practicing two forms of contraception. Sexually active male participants must agree to use a physical barrier method (male latex rubber condom with or without spermicide). Patients with well controlled HIV infection are eligible if their CD4 count is >499/cu mm and viral load is < 50 copies/ml. Pre-certification for the 90Y TARE should be performed prior to enrollment on this study. All patients must be informed of the investigational nature of this study and must have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients who have had major surgery within 4 weeks prior to entering the study or those who have not recovered from complications from a surgery more than 4 weeks earlier. Patients may not be receiving any other investigational agents. Patients must not have any grade III/IV cardiac disease as defined by the New York Heart Association (NYHA) Criteria Patients must NOT have liver disease such as cirrhosis or sever hepatic impairment as defined by Child-Pugh Class B or C Pregnant women are excluded from this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 90Y TARE with Gemcitabine and Cisplatin<br>90Y TARE will be given on day 3 or 4 of cycle 1 and start at 75% of the dose calculated by the body surface area formula and escalated by 25% per cohort in combination with cisplatin 25 mg/m2 and gemcitabine 300 mg/m2 in cycles 1 and 2. Once the 90Y TARE has reached the 100% dose level, the gemcitabine dose will increase to 600mg/m2 in dose level 3 and 1000mg/m2 in dose level 4. The cisplatin dose will remain at 25/mg/m2. For all dose levels, from cycle 3 to cycle 8, the cisplatin dose will be 25mg/m2 and the gemcitabine dose will be 1000mg/m2. | Device: SIR-Spheres microspheres (Yttrium-90 Microspheres)<br>* On Day 3 or 4 of cycle 1 90Y TARE will be administered<br>* Other names: 90Y TARE;Drug: Gemcitabine<br>* On days 1 and 8 of each cycle (21 days) Gemcitabine will be administered. Treatment may last up to 8 cycles<br>Drug: Cisplatin<br>* On days 1 and 8 of each cycle (21 days) Cisplatin will be administered. Treatment may last up to 8 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence or absence of a dose limiting toxicity (DLT) of 90Y TARE in combination with gemcitabine and cisplatin. | A continual reassessment method (CRM) design will be used to identify the maximum-tolerated dose (MTD) | 6 weeks of study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intrahepatic cholangiocarcinoma, cholangiocarcinoma, 90Y TARE, radioembolization, gemcitabine and cisplatin