6th Annual Brain Tumor Conference: Experimental Therapies

Experimental approaches in the Treatment of Malignant Gliomas
Best Available Care
Advantages: known benefit, well described side effects
Disadvantages: known benefit
Experimental
- novel mechanism of action, hope, expands knowledge
Disadvantages: phase 1 study not likely to provide a benefit, trying to find dose limit toxicity, unknown side effects
Goals of phase 1 studies: define dose (max tolerated dose vs. biologically effective dose); define toxicities; determine benefits; no controls (no placebo group)
Phase 2 (dosage set): define effect against tumor at set dose, define side effects, may use historical control vs. no control
Phase 3: define benefits against standard care (at least two arms -standard or experimental); benefits: shrinkage of tumor; survival; quality of life.
Informed Consent: defines the study in detail; defines the potential side effects; the cost to the patient; defines your rights; defines your physicians interests
When we enter experimental approaches, there a group of drugs called small molecular inhibitors. These drugs effected by liver metabolism. Anti seizure medicines that activate the liver often prevent you from participating in certain drug trials.
Try to define what is the biological active dose. Go through initial treatment at some point may have recurrence. Instead of going straight to surgery, we try an experimental drug then do surgery. When we get tumor sample, we can test how much of drug in tumor and if it blocked any pathways. This helps us to determine dosage for that patient in the future.
Cytostatic agents plus Temodar for recurrent or progressive GBM. Determine effectiveness by 6 month progression free survival.
Experimental approaches in neuro-oncology
- radiation
Sensitizers: GD TEX; ways to increase oxygen(RSR 13, Bovine hemoglobin); radio-labeled antibody (anti-tenasin, chlorotoxin, scorpion venom);Avastin to increase oxygen; AQ4N
Protection: stem cell research; growth factors
- Convection based delivery: conjugated proteins, chemotherapy Made proteins that match receptors on the tumor and not normal brain and gets pulled into the tumor to kill the cancer cell (put in with catheters) TP-38
- Gene/Viral Therapy: HSV tk (herpes - not so effective in humans, delivery impaired possibly by our own immune system); Oncolytic Virus - leads to activation of viruses to help kill the cancer cells (Onyx 15, Reovirus, NewCastle)
- Immune therapy (your own body helps fight tumor): Dendritic cell; antisense; TIL; LAK
- Focal Molecular Therapy: Receptor; cell cycle; signal transduction; angiogenesis
- combinational therapy: chemo/biologic, etc.
Combination Therapy from NABTC
Tarceva CCI-779
Sorafinib and R115777
Sorafinib and Tarceva
Sorafinib and CCI-779

ABC2 Clinical Trials
Avastin vs. Avastin CPT-11
Rad001

A lot of trials don't make it to phase 3 because the can't show that they are better than standard treatment (20% progression free for 6 months).
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UCLA Database project
Approach
- consented patient
- tissue samples
- clinical data
- imaging
- genomic
- gene expression
- protein
- cell lines

Created a computer environment where clinical & research needs are equally served. Software to help: mobile hand helds, PC, research edition to take data out of lab info. Real-time data screening to apply filters to data center to customize which data sets to return. Once results are returned, users are able to customize what visualization options to view the data set in. The data being gathered will help to determine similarities among patients and their treatments to help get data that may increase individualized therapies.