RAD001 in Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Laboratory studies have shown that RAD001 can prevent cells from multiplying. Consequently, the study drug is being tested in medical conditions in which excessive cell multiplication (as in cancer) needs to be stopped. The main purpose of this research study is to find the highest dose of RAD001 that can be given safely (without causing severe side effects) and to learn the effects (good or bad) RAD001 has on participants with liver cancer.

Detailed Description
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Participants will be given a supply of the study drug RAD001 to be taken at home. They will be asked to take the study drug every morning on an empty stomach and will be given a study drug diary to record the time/date each time they take RAD001. Each 6 week period of time is called a cycle of study treatment. We are looking for the highest dose of RAD001 that can be given safely. Therefore not every participant will receive the same dose of RAD001. Participants will come to the clinic every other week. At each of these visits, a physical examination and blood tests will be performed. A CT and MRI will be repeated every 6 weeks during the first 3 cycles of treatment then every 12 weeks thereafter.

Official Title
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A Phase I/II Study of RAD001 in Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: RAD001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable of metastatic HCC. Patients must have prior core biopsy to confirm the diagnosis of HCC and have archived tissues available for correlative studies At least one measurable site of disease according to RECIST criteria that has not been previously irradiated. If it has had previous radiation to teh marker lesion(s), there must be evidence of progression since the radiation 0-2 prior systemic chemotherapy and biologic regimens for hepatocellular carcinoma Patients with prior chemoembolization history can participate in the study if the chemoembolization was performed more than 4 weeks ago and patients must have measurable disease outside of prior chemoembolization field 18 years of age or older Minimum of 4 weeks since any major surgery or completion of radiation Minimum of 4 weeks since completion of all prior systemic anticancer therapy ECOG performance status of 0-2 CLIP score of equal to or less then 3 Adequate bone marrow, liver and renal function as outlined in the protocol Exclusion Criteria: Prior treatment with any investigational drug within the preceding 4 weeks Chronic treatment with systemic steroids or another immunosuppressive agent Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases Patients with any severe and/or uncontrolled medical conditions or other condition that could affect participation in the study Known history of HIV seropositivity Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 Active, bleeding diathesis Women who are pregnant or breast feeding Patients who have received prior treatment with an mTor inhibitor Patients with known hypersensitivity to RAD001 or other rapamycins or its excipients History of non-compliance to medical regimens Patients with a positive dipstick for urine protein (reading of 2+ or greater) will then undergo a 24-hour urine collection for protein. If patients have a 2g or greater of protein/24hr, they will be excluded from the 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: RAD001<br>Patients will receive RAD001 10 mg/day orally (6 weeks/cycle). Patients will be continued on treatment until disease progression, limiting toxicity, patient withdrawal of consent, or death. | Drug: RAD001<br>* Oral pills taken daily in a 42-day cycle (6 weeks). Cycles will be repeated every 42 days<br>* Other names: Everolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose of RAD001 in Patients With Advanced Hepatocellular Carcinoma (HCC). |  | 2 years | 
| Progression-free Survival Rate at 24 Weeks | Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions This information will be collected during two years of patient participation. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Adverse Events Who Were Treated With RAD001 for Advanced HCC | Everolimus given at 10 mg/day as a single agent was well tolerated in patients with advanced HCC. | 2 years | 
| Overall Response Rate | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 2 years | 
| Time to Progression | 3.9 months with a CI of 21- | 2 years | 
| Overall Survival | The median overall survival was 8.4 months (95% CI, 3.9-21.1 months). Only 2 ((8 %) patients were progression-free at 24 weeks. The study did not proceed to the second stage of the phase 2 portion of the study. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver cancer, RAD001