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CompletedNCT00516165Updated Feb 7, 2017Results posted

RAD001 in Advanced Hepatocellular Carcinoma

A Phase 1/2 interventional study of RAD001 in Hepatocellular Carcinoma, sponsored by Massachusetts General Hospital. Completed at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-02-07.

Sponsored by Massachusetts General Hospital · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
28
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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.
02

Conditions studied

  • Hepatocellular Carcinoma

Keywords

  • liver cancer
  • RAD001
03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 28 is below the median of 45 across 5,170 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

Massachusetts General Hospital is the lead sponsor of 2,536 studies on the registry; 446 are open to participants now.

Of its 214 completed or terminated interventional studies of FDA-regulated products, 161 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
28 participants (actual)

Study arms

  • 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.

    Drug: RAD001

Interventions

  • DrugRAD001

    Oral pills taken daily in a 42-day cycle (6 weeks). Cycles will be repeated every 42 days

    Also known as: Everolimus

06

What researchers measure

Primary outcomes

  1. Maximum Tolerated Dose of RAD001 in Patients With Advanced Hepatocellular Carcinoma (HCC).

    Time frame: 2 years

  2. 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.

    Time frame: 2 years

Secondary outcomes

  1. 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.

    Time frame: 2 years

  2. 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.

    Time frame: 2 years

  3. Time to Progression

    3.9 months with a CI of 21-

    Time frame: 2 years

  4. 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.

    Time frame: 2 years

07

Results

Posted Feb 7, 2017

Participant flow

Participant flow — Overall Study
MilestoneRAD001
Started28
Completed28
Not completed0

Outcome measures

PrimaryMaximum Tolerated Dose of RAD001 in Patients With Advanced Hepatocellular Carcinoma (HCC).
Time frame:
2 years
Reported as:
Number · mg
Maximum Tolerated Dose of RAD001 in Patients With Advanced Hepatocellular Carcinoma (HCC).
mgRAD001
Maximum Tolerated Dose of RAD001 in Patients With Advanced Hepatocellular Carcinoma (HCC).10
Statistical analysis
  • RAD001 · Kaplan Meier · p = 0.05
PrimaryProgression-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.

Time frame:
2 years
Reported as:
Median · months
Progression-free Survival Rate at 24 Weeks
monthsRAD001
Progression-free Survival Rate at 24 Weeks3.8 (2.1 to 4.6)
Statistical analysis
  • RAD001 · Kaplan-Meier · p = <0.05
SecondaryNumber 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.

Time frame:
2 years
Reported as:
Count of participants · Participants
Number of Patients With Adverse Events Who Were Treated With RAD001 for Advanced HCC
ParticipantsRAD001
Number of Patients With Adverse Events Who Were Treated With RAD001 for Advanced HCC28
Statistical analysis
  • RAD001 · Kaplan-Meier · p = <0.05
SecondaryOverall 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.

Time frame:
2 years
Reported as:
Number · percentage of patient response
Overall Response Rate
percentage of patient responseRAD001
Overall Response Rate4 (0.9 to 19.6)
Statistical analysis
  • RAD001 · Kaplan-Meier · p = 0.05
SecondaryTime to Progression

3.9 months with a CI of 21-

Time frame:
2 years
Reported as:
Median · month
Time to Progression
monthRAD001
Time to Progression3.9 (2.1 to 5.5)
Statistical analysis
  • RAD001 · Kaplan-Meier · p = 0.05
SecondaryOverall 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.

Time frame:
2 years
Reported as:
Median · months
Overall Survival
monthsRAD001
Overall Survival8.4 (3.9 to 21.1)
Statistical analysis
  • RAD001 · Kaplan-Meier · p = 0.05

Adverse events

Collected over October 2007 and June 2009; Participants were followed for this two year time period.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
RAD001—7/28 (25%)28/28 (100%)
Most frequent serious events
Most frequent serious events
EventRAD001
Grade 5-Death within 30 days.General disorders4/28
Grade 3 Encephalopathy-unrelatedNervous system disorders1/28
Grade 4 AnemiaMetabolism and nutrition disorders1/28
Grade 4 ThrombocytopeniaMetabolism and nutrition disorders1/28
Grade 4-HypoxiaGeneral disorders1/28
Grade 4 BilirubinGastrointestinal disorders1/28
Grade 4 HypophosphatemisBlood and lymphatic system disorders1/28
Respiratory failureGeneral disorders1/28
Grade 4 elevated SGOTBlood and lymphatic system disorders1/28
Most frequent other events
Showing 10 of 33
Most frequent other events
EventRAD001
FatigueGeneral disorders13/28
HyperglycemiaMetabolism and nutrition disorders12/28
AnemiaBlood and lymphatic system disorders11/28
DiarrheaGastrointestinal disorders11/28
LeukopeniaInvestigations10/28
PlateletsInvestigations10/28
Aspartate transaminaseInvestigations9/28
HyponatremiaMetabolism and nutrition disorders9/28
AnorexiaMetabolism and nutrition disorders9/28
LymphopeniaBlood and lymphatic system disorders8/28

Baseline characteristics

Age, Continuous
Age, Continuous(years)RAD001
Median65 (33 to 81)
Age, Categorical
Age, Categorical(Participants)RAD001
<=18 years0
Between 18 and 65 years13
>=65 years15
Gender
Gender(Participants)RAD001
Female10
Male18
Region of Enrollment
Region of Enrollment(participants)RAD001
United States28
08

Study locations

3 sites
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02215, United States
09

References and documents

Publications

  • 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. PubMed 19192962 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 7, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00516165
Lead sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, Novartis
Responsible party
Andrew X. Zhu, MD (Principal Investigator, Massachusetts General Hospital) — Principal investigator
First posted
Aug 15, 2007
Start date
Aug 2007
Primary completion
Jan 2010
Completion
Nov 2011
Results posted
Feb 7, 2017
Last update
Feb 7, 2017

Study contacts

Andrew X. Zhu, MD, PhD
principal investigator · Massachusetts General Hospital

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Dec 2016. You cannot join it, but the record below documents what was studied.

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