- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00516165
RAD001 in Advanced Hepatocellular Carcinoma
December 14, 2016 updated by: Andrew X. Zhu, MD, Massachusetts General Hospital
A Phase I/II Study of RAD001 in Advanced Hepatocellular Carcinoma
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.
Study Overview
Detailed Description
- 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.
Study Type
Interventional
Enrollment (Actual)
28
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, United States, 02115
- Dana-Farber Cancer Institute
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: RAD001
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.
|
Oral pills taken daily in a 42-day cycle (6 weeks).
Cycles will be repeated every 42 days
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose of RAD001 in Patients With Advanced Hepatocellular Carcinoma (HCC).
Time Frame: 2 years
|
2 years
|
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Progression-free Survival Rate at 24 Weeks
Time Frame: 2 years
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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
Time Frame: 2 years
|
Everolimus given at 10 mg/day as a single agent was well tolerated in patients with advanced HCC.
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2 years
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Overall Response Rate
Time Frame: 2 years
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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.
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2 years
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Time to Progression
Time Frame: 2 years
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3.9 months with a CI of 21-
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2 years
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Overall Survival
Time Frame: 2 years
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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.
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2 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Andrew X. Zhu, MD, PhD, Massachusetts General Hospital
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2007
Primary Completion (Actual)
January 1, 2010
Study Completion (Actual)
November 1, 2011
Study Registration Dates
First Submitted
August 13, 2007
First Submitted That Met QC Criteria
August 13, 2007
First Posted (Estimate)
August 15, 2007
Study Record Updates
Last Update Posted (Estimate)
February 7, 2017
Last Update Submitted That Met QC Criteria
December 14, 2016
Last Verified
December 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Liver Neoplasms
- Carcinoma
- Carcinoma, Hepatocellular
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Everolimus
Other Study ID Numbers
- 06-352
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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