Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Hematinics

All Drugs and Chemicals

Antineoplastic Agents

Liver Extracts

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Dose escalation (100, 200 and 300 mg/day) over 2 hr infusion, once weekly over 21 days (Day 1, 8, 15)

AEG35156 antisense IV infusion

Sorafenib will be administered at 400 mg BID every day

Ann Shing Lee, MBChB(CUHK), FHKAM(Rad)

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.

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)

13 patients were enrolled into the phase 1 dose escalation part of the study. The recommended dose was determined to be 300 mg.

Chinese University of Hong Kong

Aegera Therapeutics

Jacques Jolivet, MD, Senior VP Clinical

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, B-Cell

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Lymphoma, Non-Hodgkin

Leukemia, B-Cell

Chronic Disease

Disease Attributes

B-cell Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Indolent B Cell Lymphoma

Antiemetics

Gastrointestinal Agents

Antirheumatic Agents

Dimenhydrinate

Allopurinol

Single agent AEG35156 as 2hr IV infusion, weekly dosing in Patients with relapsed or refractory chronic lymphocytic leukemia and indolent B-cell lymphomas

AEG35156 will be given as a 2-hour intravenous infusion (escalating dose 50, 100, 150, 200, 250 and 300 mg) once weekly on Day 1, Day 8 and Day 15. One cycle of therapy will consist of 21 days. Patients will be treated until disease progression.

* Patients must be pretreated for at least three days with allopurinol prior to the first dose of AEG35156 and throughout protocol therapy.
* Patients must be hydrated with 1 L of normal saline prior AEG35156 infusion

John Sweetenham, MD

AEG35156 has shown early evidence of activity in patients with advanced indolent B-cell lymphomas in Phase 1 trials and merits further evaluation in this disease. This trial is designed to determine the recommended dose of AEG35156 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and indolent B-cell lymphomas.

Apoptotic induction in cancer cells is a sought after therapeutic goal. Most successful anticancer agents activate apoptosis pathways in the cancers they treat. Apoptotic pathways in cells appear to converge on a single family of enzymes, the caspases, which are proteases that dismantle the cell in an orderly, non-inflammatory fashion, resulting in cell death. The X-linked Inhibitor of Apoptosis (XIAP) is the only known cellular inhibitor of caspases, its over expression thereby blocking the principal means of apoptosis. A wide range of evidence indicates that cellular overexpression of members of the IAP family is a fundamental means by which many cancer cells evade death, even in the presence of strong extrinsic (death receptor-mediated) and intrinsic (mitochondria-mediated) apoptotic cues. The inhibition of cellular XIAP activity, specifically in cancer cells under stress and primed for apoptosis by chemotherapeutic agents, is viewed as a powerful means of tipping the balance towards cell death. In particular, XIAP has been shown to be overexpressed in lymphoma. 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. AEG35156 has shown early evidence of activity in patients with advanced indolent B-cell lymphomas in Phase 1 trials and merits further evaluation in this disease.

A Phase 1-2, Multicenter, Open-Label Study of AEG35156 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia and Indolent B-Cell Lymphomas

AEG35156-204: A Phase 1-2, Multicenter, Open-Label Study of the X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia and Indolent B-Cell Lymphomas

The Leukemia and Lymphoma Society

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
XIAP Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)	NCT00882869	Advanced Hepato...	AEG35156 antise... Sorafenib	18 Years -	Aegera Therapeutics
A Phase 1-2, Multicenter, Open-Label Study of AEG35156 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia and Indolent B-Cell Lymphomas	NCT00768339	Leukemia, Lymph... Lymphoma, B-Cel...	AEG35156 antise...	18 Years -	Aegera Therapeutics
A Phase 1-2, Multicenter, Open-Label Study of AEG35156 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia and Indolent B-Cell Lymphomas	NCT00768339	Leukemia, Lymph... Lymphoma, B-Cel...	AEG35156 antise...	18 Years -	Aegera Therapeutics
XIAP Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)	NCT00882869	Advanced Hepato...	AEG35156 antise... Sorafenib	18 Years -	Aegera Therapeutics
A Phase 1-2, Multicenter, Open-Label Study of AEG35156 in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia and Indolent B-Cell Lymphomas	NCT00768339	Leukemia, Lymph... Lymphoma, B-Cel...	AEG35156 antise...	18 Years -	Aegera Therapeutics
XIAP Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)	NCT00882869	Advanced Hepato...	AEG35156 antise... Sorafenib	18 Years -	Aegera Therapeutics

Spots Global Cancer Trial Database for aeg35156 antisense iv infusion