RAD001 in Advanced Hepatocellular Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00516165
Recruitment Status : Completed
First Posted : August 15, 2007
Results First Posted : February 7, 2017
Last Update Posted : February 7, 2017
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Information provided by (Responsible Party):
Andrew X. Zhu, MD, Massachusetts General Hospital

August 13, 2007
August 15, 2007
December 3, 2014
February 7, 2017
February 7, 2017
August 2007
January 2010   (Final data collection date for primary outcome measure)
  • Maximum Tolerated Dose of RAD001 in Patients With Advanced Hepatocellular Carcinoma (HCC). [ Time Frame: 2 years ]
  • Progression-free Survival Rate at 24 Weeks [ Time Frame: 2 years ]

    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.

  • To determine the maximum tolerated dose of RAD001 in patients with advanced hepatocellular carcinoma (HCC).
  • To determine progression-free survival rate at 24 weeks [ Time Frame: 24 weeks ]
Complete list of historical versions of study NCT00516165 on Archive Site
  • 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.
  • Overall Response Rate [ Time Frame: 2 years ]
    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.
  • Time to Progression [ Time Frame: 2 years ]
    3.9 months with a CI of 21-
  • Overall Survival [ Time Frame: 2 years ]
    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.
  • To assess the safety and toxicity of RAD001 in patients with HCC
  • To assess the response rate and duration of response of RAD001 iin HCC, time to tumor progression, and overall survival of this population
Not Provided
Not Provided
RAD001 in Advanced Hepatocellular Carcinoma
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.
  • 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.
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Hepatocellular Carcinoma
Drug: RAD001
Oral pills taken daily in a 42-day cycle (6 weeks). Cycles will be repeated every 42 days
Other Name: Everolimus
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.
Intervention: Drug: RAD001
Treiber G. mTOR inhibitors for hepatocellular cancer: a forward-moving target. Expert Rev Anticancer Ther. 2009 Feb;9(2):247-61. doi: 10.1586/14737140.9.2.247. Review.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
November 2011
January 2010   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Plan to Share IPD: No
Andrew X. Zhu, MD, Massachusetts General Hospital
Massachusetts General Hospital
  • Dana-Farber Cancer Institute
  • Beth Israel Deaconess Medical Center
  • Novartis
Principal Investigator: Andrew X. Zhu, MD, PhD Massachusetts General Hospital
Massachusetts General Hospital
December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP