NCT00390195

Brief Summary

The mTOR has been examined in hepatocellular carcinomas as well. This pathway is up-regulated in a proportion of hepatocellular carcinoma (HCC) and that rapamycin inhibits cell proliferation and blocks S6K phosphorylation. Inhibition of mTOR had been shown to suppress substantially the liver tumor growth. Nevertheless, inhibition of mTOR was demonstrated to have a clinical response in some cancer types. These reports imply that inhibition of mTOR could be a promising therapeutic strategy in the treatment of HCC. Therefore, we hypothesize that RAD001, a rapamycin analog, can inhibit the mTOR, and subsequently suppress the liver tumor in the treatment of HCC patients. This study is aimed to investigate the safety, efficacy, pharmacokinetics, pharmacogenetics and feasibility of RAD001 in advanced HCC patients. This study will be a randomized phase I study with dose escalation and subsequently a phase II study of intent to treat, as well as pharmacokinetic, pharmacogenetic and surrogate marker study of RAD001.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
134

participants targeted

Target at P75+ for phase_1 hepatocellular-carcinoma

Timeline
Completed

Started Oct 2006

Typical duration for phase_1 hepatocellular-carcinoma

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2006

Completed
16 days until next milestone

First Submitted

Initial submission to the registry

October 17, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 19, 2006

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2010

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2011

Completed
Last Updated

July 2, 2009

Status Verified

June 1, 2009

Enrollment Period

3.7 years

First QC Date

October 17, 2006

Last Update Submit

June 29, 2009

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinomaRAD001RapamycinRandomizePhase IPhase IIPharmacokinetics

Outcome Measures

Primary Outcomes (2)

  • Maximum tolerated dose in Phase I

    June-2008

  • Disease control rate in Phase II

    Dec-2009

Secondary Outcomes (7)

  • Angiogenic factors

    Dec-2009

  • Pharmacokinetics

    Jun-2008

  • Pharmacogenetics

    Dec-2009

  • Pharmacodynamics

    Dec-2009

  • Overall survival

    Jun-2010

  • +2 more secondary outcomes

Study Arms (2)

1. Daily

EXPERIMENTAL

Taking orally the investigational drug daily

Drug: RAD001 (everolimus)

2. Weekly

EXPERIMENTAL

Taking orally the investigational drug weekly

Drug: RAD001 (everolimus)

Interventions

RAD001 (everolimus)DRUG

Arm 1: 2.5, 5, 7.5 or 10 mg of RAD001 daily

Also known as: Certican
1. Daily

Eligibility Criteria

Age20 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with measurable, metastatic or locally advanced HCC that are not feasible to have or have failed to prior local therapy (including surgical resection, transarterial chemoembolization and/or alcohol injection) are eligible.
  • The diagnosis of HCC should be established either by cyto/histology; or, by characteristic imaging studies (have to including angiography) plus serum level of AFP equal to or more than 400 ng/mL in patients with cirrhosis of the liver and/or chronic viral hepatitis B or C infection.
  • Patients must be equal to or more than 20 years of age and equal or less than 75 years of age.
  • Patients must have a performance status of ECOG score equal to or less than 2.
  • Patients must fulfill all of the following criteria: Child-Pugh's Score equal to or less than 9; serum total bilirubin level is equal to or less than 2.0 mg/dL; serum ALT level (GPT) equal to or less than 3.0 x upper normal limit; platelet are equal to or more than 50,000 / uL; WBC are equal to or more than 3,000 / uL.
  • Serum creatinine equal to or less than 2.0 x upper normal limit.
  • Life expectancy equal to or more than 12 weeks.
  • Signed informed consent.
  • Sexually active patients, in conjunction with their partner, must practice birth control during, and for 2 months after therapy.
  • Female patients at child-bearing age must have negative pregnancy test.
  • No known HIV infection.

You may not qualify if:

  • Patients with diseases which require concurrent usage of glucocorticosteroid or immunosuppressant agent(s) are not eligible.
  • Patients with concomitant active secondary malignancies, except for surgically cured carcinoma in situ of the cervix and basal or adequately treated squamous cell carcinoma of the skin, or disease-free of malignancies \< 3 years before the study, are not eligible.
  • Patients with active infection are not eligible.
  • Patients who received other rapamycin analogs before are not eligible.
  • Patients with severe cardiopulmonary diseases (including history of stable, effort-induced or unstable angina pectoris or myocardiac infarction) and other systemic diseases under poor control are not eligible.
  • Patients with history of psychiatric disorder are not eligible.
  • Patients with brain metastases are not eligible.
  • Patients who received surgery, radiotherapy except to bone, chemotherapy, immunotherapy, or other investigational drug within 4 weeks before initiating study are not eligible.
  • Patients who are pregnant, breast-feeding or not using appropriate birth control during the course of the study are not eligible.
  • Patients with significant concomitant disease that will be aggravated by the investigational drug are not eligible.
  • Patients on active treatment with inhibitors or inducers of P-glycoprotein, CYP3A4 and CYP3A5 are not eligible; a minimal of 2 weeks wash-out period will be required after stop such medications.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

National Cheng Kung University Hospital

Tainan, 704, Taiwan

RECRUITING

Tri-Service General Hospital

Taipei, 11490, Taiwan

ACTIVE NOT RECRUITING

Related Publications (8)

  • Chan S. Targeting the mammalian target of rapamycin (mTOR): a new approach to treating cancer. Br J Cancer. 2004 Oct 18;91(8):1420-4. doi: 10.1038/sj.bjc.6602162.

    PMID: 15365568BACKGROUND

  • Meric-Bernstam F, Mills GB. Mammalian target of rapamycin. Semin Oncol. 2004 Dec;31(6 Suppl 16):10-7; discussion 33. doi: 10.1053/j.seminoncol.2004.10.013.

    PMID: 15799239BACKGROUND

  • Bjornsti MA, Houghton PJ. The TOR pathway: a target for cancer therapy. Nat Rev Cancer. 2004 May;4(5):335-48. doi: 10.1038/nrc1362. No abstract available.

    PMID: 15122205BACKGROUND

  • Yee KW, Zeng Z, Konopleva M, Verstovsek S, Ravandi F, Ferrajoli A, Thomas D, Wierda W, Apostolidou E, Albitar M, O'Brien S, Andreeff M, Giles FJ. Phase I/II study of the mammalian target of rapamycin inhibitor everolimus (RAD001) in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res. 2006 Sep 1;12(17):5165-73. doi: 10.1158/1078-0432.CCR-06-0764.

    PMID: 16951235RESULT

  • Sahin F, Kannangai R, Adegbola O, Wang J, Su G, Torbenson M. mTOR and P70 S6 kinase expression in primary liver neoplasms. Clin Cancer Res. 2004 Dec 15;10(24):8421-5. doi: 10.1158/1078-0432.CCR-04-0941.

    PMID: 15623621RESULT

  • Rizell M, Lindner P. Inhibition of mTOR suppresses experimental liver tumours. Anticancer Res. 2005 Mar-Apr;25(2A):789-93.

    PMID: 15868910RESULT

  • Shiah HS, Chen CY, Dai CY, Hsiao CF, Lin YJ, Su WC, Chang JY, Whang-Peng J, Lin PW, Huang JD, Chen LT. Randomised clinical trial: comparison of two everolimus dosing schedules in patients with advanced hepatocellular carcinoma. Aliment Pharmacol Ther. 2013 Jan;37(1):62-73. doi: 10.1111/apt.12132. Epub 2012 Nov 8.

    PMID: 23134470DERIVED

  • 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.

    PMID: 19192962DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Everolimus

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

SirolimusMacrolidesLactonesOrganic Chemicals

Study Officials

  • Li-Tzong Chen, M.D., Ph.D.

    National Institute of Cancer Research, National Health Research Institutes, Taiwan

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Her-Shyong Shiah, M.D.

CONTACT

886-6-208-3422hsshiah@nhri.org.tw

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

October 17, 2006

First Posted

October 19, 2006

Study Start

October 1, 2006

Primary Completion

June 1, 2010

Study Completion

June 1, 2011

Last Updated

July 2, 2009

Record last verified: 2009-06

Locations

TW(2)