Randomized Phase I/II of RAD001 in Advanced Hepatocellular Carcinoma (HCC)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Health Research Institutes, Taiwan.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Novartis
Information provided by:
National Health Research Institutes, Taiwan
ClinicalTrials.gov Identifier:
NCT00390195
First received: October 17, 2006
Last updated: June 29, 2009
Last verified: June 2009
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: RAD001 (everolimus)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase I/II of Rapamycin Analog, RAD001, in Advanced Hepatocellular Carcinoma - With a Pharmacokinetic Study of RAD001

Resource links provided by NLM:


Further study details as provided by National Health Research Institutes, Taiwan:

Primary Outcome Measures:
  • Maximum tolerated dose in Phase I [ Time Frame: June-2008 ] [ Designated as safety issue: Yes ]
  • Disease control rate in Phase II [ Time Frame: Dec-2009 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Angiogenic factors [ Time Frame: Dec-2009 ] [ Designated as safety issue: No ]
  • Pharmacokinetics [ Time Frame: Jun-2008 ] [ Designated as safety issue: No ]
  • Pharmacogenetics [ Time Frame: Dec-2009 ] [ Designated as safety issue: No ]
  • Pharmacodynamics [ Time Frame: Dec-2009 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Jun-2010 ] [ Designated as safety issue: No ]
  • Time to tumor progression [ Time Frame: Jun-2010 ] [ Designated as safety issue: No ]
  • Tumor marker [ Time Frame: Dec-2009 ] [ Designated as safety issue: No ]

Estimated Enrollment: 134
Study Start Date: October 2006
Estimated Study Completion Date: June 2011
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1. Daily
Taking orally the investigational drug daily
Drug: RAD001 (everolimus)
Arm 1: 2.5, 5, 7.5 or 10 mg of RAD001 daily
Other Name: Certican
Experimental: 2. Weekly
Taking orally the investigational drug weekly
Drug: RAD001 (everolimus)
Arm 2: 20, 30, 50 or 70 mg of RAD001 daily
Other Name: Certican

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00390195

Contacts
Contact: Her-Shyong Shiah, M.D. 886-6-208-3422 ext 65113 hsshiah@nhri.org.tw

Locations
Taiwan
National Cheng Kung University Hospital Recruiting
Tainan, Taiwan, 704
Contact: Her-Shyong Shiah, M.D.    +886-6-208-3422 ext 65113    hsshiah@nhri.org.tw   
Principal Investigator: Li-Tzong Chen, M.D., Ph.D.         
Sub-Investigator: Jang-Yang Chang, M.D.         
Sub-Investigator: Wu-Chou Su, M.D.         
Sub-Investigator: Her-Shyong Shiah, M.D.         
Tri-Service General Hospital Active, not recruiting
Taipei, Taiwan, 11490
Sponsors and Collaborators
National Health Research Institutes, Taiwan
Novartis
Investigators
Principal Investigator: Li-Tzong Chen, M.D., Ph.D. National Institute of Cancer Research, National Health Research Institutes, Taiwan
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Cancer Research, National Health Research Instiutes, Deputy Director
ClinicalTrials.gov Identifier: NCT00390195     History of Changes
Other Study ID Numbers: CRAD001C2453
Study First Received: October 17, 2006
Last Updated: June 29, 2009
Health Authority: Taiwan: Department of Health

Keywords provided by National Health Research Institutes, Taiwan:
Hepatocellular carcinoma
RAD001
Rapamycin
Randomize
Phase I
Phase II
Pharmacokinetics

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on September 16, 2014