Study of Gemcitabine With TheraSphere® (Yttrium-90)in Patients With Hepatic Tumors of Pancreatobiliary Origin

Study Overview
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Brief Summary
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Therasphere is a form of treatment that has been designed to selectively deliver radiation to the cancer within the patient's liver. This form of treatment has been used in a number of clinical trials and has been approved for use in the treatment of liver cancer. The investigators want to test the safety of using Gemcitabine (a chemotherapy drug) with TheraSphere (radioactive beads that are injected directly into the blood vessel supplying the tumor in the liver) in patients with advanced pancreatobiliary tumors such as pancreatic cancer or cholangiocarcinoma (bile duct tumors) involving the liver.

Detailed Description
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Patients with liver predominant cholangiocarcinoma or pancreatic cancer will be considered for the trial. The patients wre being treated in groups of thre patients. Each three patients receive a pre-specified dose of gemcitabine with full dose radioembolization using theraspheres. If no significant side effects are observed then three additional three patients will be treated with a higher dose of gemcitabine. The purpose to identify the highest dose of gemcitabine that can be safely combined with theraspheres.

Official Title
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Phase I Trial of Gemcitabine With TheraSphere® (Yttrium-90) in Patients With Hepatic Tumors of Pancreatobiliary Origin

Conditions
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Pancreatic Neoplasms, Cholangiocarcinoma

Intervention / Treatment
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* Drug: Gemcitabine with TheraSphere


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis of pancreatic cancer or cholangiocarcinoma Liver predominant disease defined as - Cholangiocarcinoma: liver disease should be unresectable - Limited extra hepatic metastasis defined as: i. Lung metastasis: 6 or less nodules with no nodule greater than 1.5 cm. ii. Abdominal lymph nodes iii. Pancreatic primary as long as the size is less than 4 cm in size iv. Bone metastasis No prior systemic therapy for advanced stage disease Measurable target tumors using standard imaging techniques Lung shunting less than 20% ECOG performance status 0-1 (See Appendix ) Age ≥ 18 years No other investigational agents while on protocol Signed informed consent Exclusion Criteria: Inadequate hepatic function: AST/ALT > five times upper limit of normal, Bilirubin >2.0 mg/dl or history of hepatic encephalopathy Inadequate renal function Creatinine > 2.0 mg/dL Inadequate bone marrow function: platelets < 100,000/mL or absolute neutrophil count <1500/mL Contraindication to angiography Prior external beam radiotherapy to the upper abdomen Clinical evidence of peritoneal metastasis or ascites Patients with extensive tumor replacement in the liver defined as >50% of liver involved with tumor Any serious ongoing extra-hepatic disease such as infections.

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: Gemcitabine with TheraSphere<br> | Drug: Gemcitabine with TheraSphere<br>* Gemcitabine dose will be escalated and combined with therasphere.<br>* Other names: Gemcitabine- Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The maximum tolerated dose of gemcitabine when given in combination with therasphere | Patients will receive full dose therasphere. The gemcitabine dose will start out low and the dose will increase after first 3 patients if no significant side effects are observed. The investigators will continue to increase the dose of gemcitabine as long as the investigators do not observe side effects or until we reach full dose of gemcitabine. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicities (side effects) experienced by patients on the trial | Any side effect experienced on the trial will be graded according to the grading system developed by the national cancer institute. The number of patients with each side effect will be calculated. | 90 days | 
| Tumor response rate when treated with gemcitabine and Therasphere using CT scan and F18-FDG-PET scan . | Patients will receive a PET CT prior to treatment and then another PET CT scan at completion day 78. Comparison of tumor size and uptake of FDG will be performed using standard RECIST criteria | 78 days | 
| The progression free of patients treated on the trial | The investigators will follow patients with serial cross sectional (CT or MRI) scans. If the tumor shows growth on the scan then the investigators will calculate the time it took for the tumor to grow. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic neoplasms, Cholangiocarcinoma