Study of XIAP Antisense for Advanced Cancers

Study Overview
=================
Brief Summary
-----------------
This study is designed to find the maximum tolerated dose, safety and toxicity profile, and to identify any dose limiting toxicities of AEG35156 administered in 2-hour infusions to patients with advanced cancers.

Detailed Description
-----------------
This is a Phase I study, single-arm, open-label, dose escalation study to establish the recommended dose and activity of AEG35156 administered as a 2-hour daily infusion over 3 days initially followed by weekly 2-hour intravenous infusions in patients with advanced cancers. Subjects eligible for study entry must have proven advanced or metastatic cancer refactory to conventional treatment or for which no conventional therapy exists. The starting dose will be a fixed dose of 60 mg/day with escalation by steps of 50 to 100% in successive cohorts. Approximately of 30 patients will be entered in the study to determine the maximum tolerated dose.

Official Title
-----------------
A Phase I Trial of AEG35156 Administered by 2-Hour Intravenous Infusion in Patients With Advanced Cancers

Conditions
-----------------
Advanced Cancer

Intervention / Treatment
-----------------
* Drug: AEG35156


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: histologically proven diagnosis of advanced or metastatic cancer (including solid tumours and lymphoma) refractory to conventional treatment, or for which no conventional therapy exists with life expectancy of at least 12 weeks ECOG performance status of 0 or 1 hematological and biochemical indices as specified within one week prior to treatment Exclusion Criteria: known bleeding diathesis or concurrent treatment with anticoagulants primary brain tumours or brain metastases radiotherapy (except palliative), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas and mitomycin-C) all toxic manifestations of previous treatment must have resolved (excepting alopecia or certain Grade 1 toxicities) pregnant or lactating women major thoracic and/or abdominal surgery in the preceding 4 weeks high medical risks from non-malignant systemic disease including uncontrolled infection hepatitis B, C or Human Immunodeficiency Virus allergic history to antisense agents

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: AEG35156|weekly IV solution infused over 2 hrs|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose level at which AEG35156 is well tolerated based upon development of toxicities during the first cycle of therapy unless delayed or cumulative toxicity is encountered. Assessments done weekly. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the impact of AEG35156 on inhibition and apoptosis in tumour biopsies or circulating tumour cells. |  | 1 year | 
| Determine the occurence of XIAP knockdown in peripheral blood mononuclear cells. |  | 1 year | 
| Determine the plasma pharmacokinetic profile of AEG35156. |  | 1 year | 
| Determine the possible anti-tumour activity of XIAP. |  | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cancer, solid tumours, refractory, antisense, oligonucleotide