Study of Sorafenib With Combination of Thalidomide in Hepatocellular Carcinoma (HCC)

This study has been terminated.
(Two patients in the first dose level be counted as reaching DLT. DSMB recommend terminated early this trial.)
Sponsor:
Collaborators:
National Cheng-Kung University Hospital
Chang Gung Memorial Hospital
Information provided by:
National Health Research Institutes, Taiwan
ClinicalTrials.gov Identifier:
NCT00971126
First received: July 1, 2009
Last updated: July 20, 2011
Last verified: September 2009
  Purpose

The purpose of this phase I study is to determine the maximal tolerable dose (MTD) of thalidomide (THADO®) in combination with fixed dose of sorafenib (NEXAVAR®) for the treatment of advanced or metastatic HCC.

The Phase II purpose of this study is to determine the disease control rate (complete response + partial response + stable disease) for at least 4 months of sorafenib (NEXAVAR®) plus phase I determined MTD of thalidomide (THADO®) in patients with advanced or metastatic HCC.


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: sorafenib (Nexavar®), thalidomide (Thado®)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Sorafenib With Combination of Thalidomide in Advanced or Metastatic Hepatocellular Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Terms of efficacy assessment: objective tumor response, overall survival, progression-free survival. Terms of safety assessment: adverse effects, laboratory values. [ Time Frame: The overall survival will be measured from the time the patient has started protocol treatment to the date of the patient's death. 2. An interim analysis of safety profiles will be reviewed by safety committee. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 3
Study Start Date: July 2009
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Group Assignment Drug: sorafenib (Nexavar®), thalidomide (Thado®)

Phase I Fixed dose of Sorafenib 800mg/day (400mg, p.o., bid); and Escalation dose of Thalidomide at dose Level I: 50 mg/day (50mg, p.o., qd); Level II: 100 mg/day (50mg, p.o., bid); Level III: 150 mg/day (100mg/50mg, p.o., bid); Level IV: 200 mg/day (100mg, p.o., bid).

Phase II Fixed dose of Sorafenib 800mg/day (400mg, p.o., bid); and MTD of Thalidomide at phase I study.

Other Name: Nexavar®), Thado®

Detailed Description:

This is a non-randomized, open-labeled, single-arm, multi-center, phase I /II clinical study. The Phase I purpose of this study is to determine the maximal tolerable dose (MTD) of thalidomide (THADO®) in combination with fixed dose of sorafenib (NEXAVAR®) for the treatment of advanced or metastatic HCC, and the dose-limiting toxicity (DLT) profiles and other toxicity profiles in patients receiving fixed dose of sorafenib (NEXAVAR®) plus escalating dose of thalidomide (THADO). The Phase II primary objective of this study is to determine the disease control rate (complete response + partial response + stable disease) for at least 4 months of sorafenib (NEXAVAR®) plus phase I determined MTD of thalidomide (THADO®) in patients with advanced or metastatic HCC. The Phase II secondary objective of this study is to determine the objective tumor response rate, the time to tumor progression, the progression-free survival, the overall survival, and the safety and adverse event profiles, the changes of circulating biomarkers relating to angiogenesis and their correlation with disease control rate.

The sample size are required up to 24 patients for the phase I study and 53 patients for the phase II study.

Sorafenib (NEXAVAR®): supplied to Good Manufacturing Practice standards by Bayer Health Care, Taiwan as a film-coated tablet, each of which contains sorafenib tosylate (274mg) equivalent to 200 mg of sorafenib. Thalidomide (THADO®): supplied to Good Manufacturing Practice standards by TTY Biopharm Co., Ltd. as a white-yellow capsule, each of which contains 50 mg of thalidomide.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be at least 18 years of age.
  • With histologically or cytologically documented HCC or clinically diagnosed HCC.
  • Advanced (surgically unresectable and unsuitable for local therapy), and/or metastatic HCC, and/or patient refused local therapy.
  • Performance status of ECOG score 0-2.
  • Life expectancy of at least 12 weeks.
  • At least one tumor lesion that meets both of the following criteria:

    • measurable (must be by CT-scan or MRI) in at least one dimension according to RECIST;
    • the lesion has not been previously treated with local therapy, such as radiation therapy, hepatic arterial (chemo) embolization, radiofrequency ablation, and percutaneous interventional therapy.
  • Previous local therapy, such as radiotherapy, hepatic arterial (chemo)embolization, radiofrequency ablation, percutaneous interventional therapy, is allowed but the treatment must be completed at least 4 weeks prior to the baseline scan.
  • Patients have adequate bone marrow reserves defined as:

    • ANC ≧ 1,500/μl;
    • Platelets count ≧ 75,000/μl;
    • Hemoglobin ≧ 8.5 g/dl.
  • Adequate liver and renal functions defined as:

    • Child-Turcotte-Pugh score of 7 or lower (class A and well-compensated class B);
    • Liver transaminase (ALT) ≦ 5 x upper limit of normal (ULN);
    • Serum total bilirubin ≦ 3mg/dl;
    • Serum albumin ≧ 2.8 g/dl;
    • Prothrombin time (PT)-internal normalized ration (INR) ≦ 2.3 or partial thrombin time (PTT) ≦ 6 seconds above control;
    • Serum creatinine ≦ 1.5 x ULN.
  • Women of childbearing potential and men must agree to use adequate contraception, prior to study entry, during treatment, and at least 3 months after last dose of treatment.
  • Patients must understand the protocol and sign a written informed consent.

Exclusion Criteria:

  • Previous use of systemic anti-cancer therapy for HCC such as chemotherapy, immunotherapy, and targeting therapy within 4 weeks to study entry.
  • Patients with prior use of investigational drugs including sorafenib and thalidomide.
  • Active cardiac disease, including CHF NYHA class > 2, active CAD, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta-blockers or digoxin, and uncontrolled hypertension.
  • Patients with hemorrhagic diathesis or have history of active bleeding with 30 days prior to study entry.
  • History of HIV infection.
  • Active or uncontrolled infections requiring antibiotics treatment.
  • Metastatic brain or leptomeningeal tumours unless the patients is > 6 months from definitive therapy, has negative imaging study within 4 weeks of study entry, and is clinically stable with respect to the tumour at the time of study entry.
  • With seizure disorder requiring medication (such as steroids or anti-epileptics).
  • History of organ allograft.
  • Undergoing renal dialysis.
  • Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bluffer tumours [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.
  • Pregnant or breast-feeding patients.
  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: NCT00971126

Locations
Taiwan
Ghang-Gung Memorial Hospital at Chia-Yi
Chia-Yi, Taiwan, 613
Sponsors and Collaborators
National Health Research Institutes, Taiwan
National Cheng-Kung University Hospital
Chang Gung Memorial Hospital
Investigators
Principal Investigator: Chung Hu Chan, MD, PHD National Health Research Institutes, Taiwan
  More Information

No publications provided

Responsible Party: National Health Research Instiutes, Taiwan, Taiwan Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00971126     History of Changes
Other Study ID Numbers: TCOGP-1209
Study First Received: July 1, 2009
Last Updated: July 20, 2011
Health Authority: Taiwan: Department of Health

Keywords provided by National Health Research Institutes, Taiwan:
hepatocellular carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Thalidomide
Sorafenib
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014