XIAP Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)
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)
1 other identifier
interventional
75
1 country
3
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2009
Typical duration for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2009
CompletedFirst Submitted
Initial submission to the registry
April 16, 2009
CompletedFirst Posted
Study publicly available on registry
April 17, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2011
CompletedJuly 13, 2011
July 1, 2011
2 years
April 16, 2009
July 12, 2011
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
To determine the recommended dose of AEG35156 in combination with sorafenib patients with advanced HCC
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
12 months
Secondary Outcomes (2)
To determine the safety profile of AEG35156 in combination with sorafenib in advanced HCC
12 months
To determine the response rate of AEG35156 in combination with sorafenib in advanced HCC
12 months
Interventions
Dose escalation (100, 200 and 300 mg/day) over 2 hr infusion, once weekly over 21 days (Day 1, 8, 15)
Eligibility Criteria
You may qualify if:
- 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
- +6 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Aegera Therapeuticslead
- Chinese University of Hong Kongcollaborator
Study Sites (3)
Tuen Mun Hospital
Tuenmen, New Territories, Hong Kong, China
Queen Elizabeth Hospital
Hong Kong, China
Queen Mary Hospital
Hong Kong, China
Related Publications (1)
Lee FA, Zee BC, Cheung FY, Kwong P, Chiang CL, Leung KC, Siu SW, Lee C, Lai M, Kwok C, Chong M, Jolivet J, Tung S. Randomized Phase II Study of the X-linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC). Am J Clin Oncol. 2016 Dec;39(6):609-613. doi: 10.1097/COC.0000000000000099.
PMID: 24977690DERIVED
MeSH Terms
Conditions
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ann Shing Lee, MBChB(CUHK), FHKAM(Rad)
Tuen Mun Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
Study Record Dates
First Submitted
April 16, 2009
First Posted
April 17, 2009
Study Start
March 1, 2009
Primary Completion
March 1, 2011
Study Completion
May 1, 2011
Last Updated
July 13, 2011
Record last verified: 2011-07