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

July 12, 2011 updated by: Aegera Therapeutics

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

75

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Hong Kong, China
        • Queen Elizabeth Hospital
      • Hong Kong, China
        • Queen Mary Hospital
    • New Territories, Hong Kong
      • Tuen Mun, New Territories, Hong Kong, China
        • Tuen Mun Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time Frame
To determine the safety profile of AEG35156 in combination with sorafenib in advanced HCC
Time Frame: 12 months
12 months
To determine the response rate of AEG35156 in combination with sorafenib in advanced HCC
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aegera Therapeutics

Collaborators

Chinese University of Hong Kong

Investigators

  • Principal Investigator: Ann Shing Lee, MBChB(CUHK), FHKAM(Rad), Tuen Mun Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

May 1, 2011

Study Registration Dates

First Submitted

April 16, 2009

First Submitted That Met QC Criteria

April 16, 2009

First Posted (Estimate)

April 17, 2009

Study Record Updates

Last Update Posted (Estimate)

July 13, 2011

Last Update Submitted That Met QC Criteria

July 12, 2011

Last Verified

July 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AEG35156-205

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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