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

Information source: Aegera Therapeutics
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Advanced Hepatocellular Carcinoma

Intervention: AEG35156 antisense IV infusion (Drug); Sorafenib (Drug)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: Aegera Therapeutics

Official(s) and/or principal investigator(s):
Ann Shing Lee, MBChB(CUHK), FHKAM(Rad), Principal Investigator, Affiliation: Tuen Mun Hospital

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.

Clinical Details

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

To determine the recommended dose of AEG35156 in combination with sorafenib patients with advanced HCC

To evaluate the efficacy of AEG35156 in combination with sorafenib based on PFS(PII) using sorafenib alone for comparison

Secondary outcome:

To determine the safety profile of AEG35156 in combination with sorafenib in advanced HCC

To determine the response rate of AEG35156 in combination with sorafenib in advanced HCC

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Locations and Contacts

Queen Elizabeth Hospital, Hong Kong, China

Queen Mary Hospital, Hong Kong, China

Tuen Mun Hospital, Tuen Mun, New Territories, Hong Kong, China

Additional Information

Starting date: March 2009
Last updated: July 12, 2011

Page last updated: August 23, 2015

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