XIAP Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)

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: NCT00882869
Recruitment Status : Completed
First Posted : April 17, 2009
Last Update Posted : July 13, 2011
Chinese University of Hong Kong
Information provided by:
Aegera Therapeutics

Brief Summary:
AEG35156 is a second generation antisense which targets XIAP mRNA to lower XIAP levels and the apoptotic threshold of cancer cells, enhancing their sensitivity to intrinsic death and chemotherapy. Advanced HCC is an attractive target for AEG35156 since XIAP is highly expressed in HCC and may prevent cancer cells from undergoing apoptosis. Second generation antisense molecules are known to accumulate in liver where AEG35156 may down regulate XIAP protein expression in HCC cells thus promoting their apoptotic death.

Condition or disease Intervention/treatment Phase
Advanced Hepatocellular Carcinoma Drug: AEG35156 antisense IV infusion Drug: Sorafenib Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1-2, Open-Label Study of The X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)
Study Start Date : March 2009
Primary Completion Date : March 2011
Study Completion Date : May 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Intervention Details:
    Drug: AEG35156 antisense IV infusion
    Dose escalation (100, 200 and 300 mg/day) over 2 hr infusion, once weekly over 21 days (Day 1, 8, 15)
    Drug: Sorafenib
    Sorafenib will be administered at 400 mg BID every day
    Other Name: nexavar

Primary Outcome Measures :
  1. To determine the recommended dose of AEG35156 in combination with sorafenib patients with advanced HCC [ Time Frame: 12 months ]
    13 patients were enrolled into the phase 1 dose escalation part of the study. The recommended dose was determined to be 300 mg.

  2. To evaluate the efficacy of AEG35156 in combination with sorafenib based on PFS(PII) using sorafenib alone for comparison [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. To determine the safety profile of AEG35156 in combination with sorafenib in advanced HCC [ Time Frame: 12 months ]
  2. To determine the response rate of AEG35156 in combination with sorafenib in advanced HCC [ Time Frame: 12 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • HCC diagnosed by:

    • Histology, or
    • AASLD Criteria in which the diagnosis is made clinically in a patient with a known hepatitis B or cirrhosis of other etiology has a liver mass of > 2cm with typical features of HCC (i.e., hypervascular with washout in the portal/venous phase) on a dynamic imaging study (contrast CT / USG / MRI) or alternatively if the AFP is >200 ng/ml.
  • The tumor is not suitable for curative treatment (resection / transplant / local ablative therapies) or the patient is medically inoperable or refuses such treatment.
  • At least one measurable lesion according to RECIST criteria.
  • Age > 18 years.
  • Life expectancy of greater than 12 weeks.
  • ECOG performance status ≤ 2 (please refer to Appendix 1).
  • Child-Pugh score A or B (please refer to Appendix 2).
  • Adequate organ functions defined as:

    • ANC ≥ 1.5 x 109/L
    • Platelet count ≥ 75 x 109/L
    • Creatinine ≤ 1.5 x ULN
    • ALT or AST < 2.5 x ULN
    • Total bilirubin < 50 μmol/L
    • INR <1.7
    • No encephalopathy clinically
    • Normal ECG
  • For women of child-producing potential, the use of effective contraceptive methods during the study.
  • Prior local therapy to tumor (e.g. surgery, RFA, PEI, chemo-embolization, radiotherapy) is allowed provided that there is a target lesion not subjected to local therapy and/or disease progression has been documented in the target lesion subjected to local therapy. The treatment must be completed at least 4 weeks and patient has recovered from all the acute toxicities of that treatment.
  • For patients with hepatitis B, the patient must receive antiviral therapy prior to or with registration.

Exclusion Criteria:

  • Child-Pugh score C.
  • Patients who have had prior systemic chemotherapy.
  • Patients who have had any other cancer related therapy including radiotherapy within 4 weeks prior to entering the study.
  • Patients receiving any other investigational agents concurrently.
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Patients who have peripheral neuropathy.
  • Uncontrolled intercurrent disease such as, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
  • Known bleeding diathesis.
  • Pregnant or nursing women. NOTE: Women of child-bearing potential must agree to use adequate contraception (sterile or surgically sterile; hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Men who are unwilling to use acceptable forms of birth control when engaging in sexual contact with women of child bearing potential.
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
  • Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.
  • Patients who are currently receiving any other investigational agent. Subjects who have used a previous antisense oligonucleotide in the last 90 days will be excluded.
  • Unwillingness or inability to comply with procedures required in this protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00882869

China, New Territories, Hong Kong
Tuen Mun Hospital
Tuen Mun, New Territories, Hong Kong, China
Queen Elizabeth Hospital
Hong Kong, China
Queen Mary Hospital
Hong Kong, China
Sponsors and Collaborators
Aegera Therapeutics
Chinese University of Hong Kong
Principal Investigator: Ann Shing Lee, MBChB(CUHK), FHKAM(Rad) Tuen Mun Hospital

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Jacques Jolivet, MD, Senior VP Clinical, Aegera Therapeutics Inc Identifier: NCT00882869     History of Changes
Other Study ID Numbers: AEG35156-205
First Posted: April 17, 2009    Key Record Dates
Last Update Posted: July 13, 2011
Last Verified: July 2011

Keywords provided by Aegera Therapeutics:
Advanced Hepatocellular carcinoma

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs