Efficacy Study of Intra-hepatic Administration of Therasphere® in Association With Intravenous Chemotherapy to Treat Cholangiocarcinoma

Study Overview
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Brief Summary
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The purpose of this study is to assess efficacy and tolerance of intra-hepatic administration of Yttrium 90-labelled microsphere (Theraspheres®, Nordion) in association with intravenous chemotherapy with Gemcitabin and Cisplatin for the treatment of intra-hepatic cholangiocarcinoma.

Official Title
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An Open-label, Multicenter, Phase II Trial, to Evaluate the Efficacy of Intra-hepatic Administration of Yttrium 90-labelled Microspheres (Therasphere®, Nordion) in Association With Intravenous Chemotherapy With Gemcitabine and Cisplatin for the Treatment of Intra-hepatic Cholangiocarcinoma, First Line.

Conditions
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Cholangiocarcinoma

Intervention / Treatment
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* Radiation: Therasphere® in association with Gemcitabine and Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed intra-hepatic cholangiocarcinoma. Measurable target of at least 2 cm diameter. Healthy liver or cirrhosis CHILD < B8. WHO-PS: 0-1. Age ≥ 18 years. Non-Metastatic disease in extra-hepatic (are permitted: local lymph nodes < 3 cm, less than 5 lung nodes < 11 mm). Creatinine clearance (calculated with Cockcroft and Gault formula) ≥ 55 ml/min, polymorphonuclear neutrophils ≥ 1500 G/L, platelets ≥ 80 G/L, prothrombin ≥ 40% (INR ≤ 2.3), serum albumin ≥ 28 g/l, serum bilirubin ≤ 3 x LSN. Pregnancy test: negative for women of childbearing potential. Reliable contraception for a childbearing couple, men and woman must have an reliable contraception during the treatment and until 6 months following the end of the treatment by chemotherapy Signed informed consent form. Patient with national health insurance. Exclusion Criteria: Pancreas cancer or duodenum cancer invading the bile duct or ampullary cancer. Cholangiocarcinoma of the bile ducts: hilar, main duct, gallbladder. Extra-hepatic metastasis (including local lymph nodes measuring > 30 mm). Primary sclerosing cholangitis. History of chemoembolization or radioembolization. Cirrhose CHILD > B7 Portal vein trunk tumoral thrombosis History of hepato-biliary neo adjuvant or palliative chemotherapy and/or radiotherapy. Contra indication of Gemcitabine and/or Cisplatin. Other invasive active cancer, excepting in situ cervical cancer and basocellular or spino cellular skin cancer treated adequately. Any history of cancer not considered as completely cured for at least one year. Technical failure of the diagnostic arteriography. Extra hepatic uptake on the pre-therapeutic scintigraphy not manageable with an arteriography. Dosimetry study predicting lung exposure > 30 Gy. Any unstable medical history (diabetes, hypertension …). History of organ transplant. Symptomatic grade 1 angina pectoris or grade ≥ 2 angina pectoris. An evolutive neuropathy. Patient who already has been involved in a clinical trial with drug intake, whether this drug was experimental or not, within 30 days before. Pregnant patient or patient with breastfeeding. Patient under administrative supervision. Regular follow-up impossible for various reasons (psychological, familial, economical, and social).

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: Therasphere®<br>Therasphere® in association with Gemcitabine and Cisplatin | Radiation: Therasphere® in association with Gemcitabine and Cisplatin<br>* Therasphere® is a radioelement<br>* Other names: 90-Yttrium theraspheres;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiological response rate to the treatment with the association of chemotherapy and radioembolization | Evaluation according RECIST 1.1 criteria. Rate will be reassessed every 8 weeks | 3 months after radioembolization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance of intra-hepatic administration of Yttrium 90-labelled microspheres in association with intravenous chemotherapy with Gemcitabine and Cisplatin assessed according NCI/CTC AE version 4. | Grade 3-4 toxicity appearance.Time between 1st treatment administration and date of 1st appearance of a grade 3-4 toxicity or date of last toxicities assessment in case no grade 3-4 toxicity | Up to 24 months | 
| Tumor markers changes (CA19.9, CEA and AFP) | Markers will be analysed every 8 weeks during treatment period and if applicable every 12 weeks after surgery | Up to 24 months | 
| Radiological response rate by the CHOI criteria | every 8 weeks and every 12 weeks after surgery if applicable | Up to 24 months | 
| Change in metabolic activity measured by TEP |  | Change from baseline in metabolic activity 15 and 24 weeks after last treatment by microspheres | 
| Changes of liver volume | Every 8 weeks during treatment and every 12 weeks after surgery if applicable | Up to 24 months | 
| Tumoral and non-tumoral dosimetric assessment of the liver | Data obtained from SPECT/CT performed at each hepatic scintigraphy | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intra-hepatic Cholangiocarcinoma treatment