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Individualized Online Clinical Trial Protocol Version 1.0


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The traditional meaning of Health 2.0, according to Jane Sarasohn-Kahn's "Wisdom of Patients" has been the use of social software and light-weight tools to promote collaboration between patients, their caregivers, medical professionals and other stakeholders in health.

http://www.chcf.org/topics/chronicdisea ... mID=133631

An example of this in cancer medicine is Individualized Online Clinical Trial Protocol Version 1.0 by the Weisenthal Cancer Group, a Phase II evaluation of individualized cancer treatment with traditional cytotoxic chemotherapy, targeted anti-kinase drugs and anti-angiogenic agents.

With most clinical trials, investigators never give out information as to how people are doing. Most trials are failures with respect to actually improving things. The world doesn't find out what happen until after a hundred or 500 or 2,000 patients are treated and then only 24 hours before the New England Journal of Medicine publication date.

Individualized Online Clinical Trial Protocol Version 1.0 is a totally transparent clinical trial. Every patient who decides to enter a study should know what happened to previous patients. Patients are treated in real time, on the Internet, with the whole world watching to see how they do. It includes weekly progress reports, and if individual patients want, their own blogs as to how they are doing.

Stages have been implemented for a rather innovative clinical trial with cell culture assays, "real time" on the Internet. The purpose of the study is to show that cell culture assay technologies for "targeted" agents really do work. The short-term future of cancer therapeutics is combinations of "targeted" agents.

http://weisenthalcancer.com:80/Study%20 ... alHome.htm

They are not "marketing" the test beyond the confines of a clinical trial, which will be the most transparent clinical trial in the history of oncology, as all results are going to be reported, in real time, on a week by week, patient by patient basis, on the website.

Call or e-mail Weisenthal Cancer Group and ask to speak with Connie Rueff, the study coordinator. She will answer any questions you may have and will help you to determine if you are a candidate for entry. (714) 596-2100 or connie@weisenthalcancer.com

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The Musella Foundation's virtualtrials.com is doing something similar to what the Weisenthal Cancer Group is doing. Their brain tumor virtual trial keeps track of patients and displays the results "real time" on the web (virtualtrials.com/volresults).

You select a tumor type (or all tumors to see more data). Then click on a treatment name and you see all patients who took that treatment + each of the other treatments. Click on a number of patients in each group and you get details of the group. Within this group display, click on a patient id and get their details.

But this is the kicker. The Musella Foundation also works on getting insurance companies to pay for these expensive combinations. The most popular one for brain tumors now is cpt-11 and Avastin. It can cost $600,000 a year (perhaps a U.S. Senator could afford that).

The Weisenthal website states there are no one-size-fits-all treatments in this trial and no patient unknowingly receives a placebo instead of a promising new drug he/she had hoped to receive. Patient outcomes will be reported online, in real-time, so patients and cancer physicians will learn immediately if and how patients are benefitting from anti-angiogenic, anti-tyrosine kinase, and standard drug combination therapies identified for them by the new test.

It is the first clinical trial in which novel combinations of emerging drugs are tested for activity in biopsy specimens obtained from each individual patient. While many of these potentially effective drugs are highly expensive, one problem has been in determining in advance who would benefit from them, how to make the drugs more effective by using them in combination. The effectiveness of these drugs can increase exponentially when they are combined with other drugs in various ways.

It is a trial in which each patient receives treatment designed for him/her alone rather than a treatment that serves the financial or research interest of the pharmaceutical company or institution which sponsors traditional clinical trials. Until this new test, no technology existed which allowed for individualized laboratory assessment of candidate drug "combinations" prior to administering them to patients.

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The CP-751,871 research is a good example of what a functional tumor cell assay does. The Pfizer press release says that the insulin-like growth factor receptor (IGF-1R) is increasingly recognized by the medical community as a relevant target for investigation in cancer research. However, there may be a lack of prognostic value of IGF-1R.

For example, Iressa is a drug that inhibits Epidermal Growth Factor Receptor (EGFR). In some cancer cells, EGFR triggers uncontrolled cell division. There are rare patients that respond very well to Iressa. However cancer cells evolve resistance to Iressa by multiple mechanisms related to genetic alterations both with the EGFR gene and at other sites. Over-activity of the insulin growth factor signaling pathway (IGR-1R) can confer resistance. Mutations involving the oncogene KRAS are also associated with resistance to Iressa.

Cancer cells often have many mutations in many different pathways, so even if one route is shut down by a targeted treatment, the cancer cell may be able to use other routes. Targeting one pathway may not be as effective as targeting multiple pathways in a cancer cell. Most cancers cannot be effectively treated with targeted drugs alone. Drugs are combined with existing ones to target the tumor more effectively.

The key to understanding the genome is understanding how cells work. The ultimate driver is functional profiling (is the cell being killed regardless of the mechanism) as opposed to targeting (does the cell express a particular target that the drug is supposed to be attacking). While a "target" tells you whether or not to give "one" drug, functional profiling can find other compounds and combinations and can recommend them from the one assay.

Cell-based functional assays are being used for screening compounds for efficacy and biosafety. The ability to track the behavior of cancer cells permits data gathering on functional behavior not available in targeting assays.

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Greg Pawelski: Most cancers cannot be effectively treated with targeted drugs alone. Drugs are combined with existing ones to target the tumor more effectively.

Thanks for the explanation re multiple targets, Greg. I've been grumbling and muttering under my breath about the failure of drug companies to offer trials whereby their product is "stand alone." Now I have a better understanding of why this rarely happens and thus will need to shift gears in my never-ending attacks on pharmaceuticals! :-)



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The vast majority of clinical trials performed are ones that test one chemotherapeutic regiman against another. Single arm clinical trials provide the tumor response evidence that is the basis for approving new cancer drugs.

With the new "targeted" drugs, there is a headlong rush to develop tests to identify molecular predisposing mechanisms whose presence still does not guarantee that a drug will be effective for an individual patient.

Nor can these genetic tests, for any patient or even large groups of patients, discriminate the potential for clinical activity among different agents, even of the same class.

The primary reason for EGFR testing in lung cancer is to determine who is most likely to benefit from a drug which is directed against the EGFR protein. There are a number of common ways to measure EGFR status on lung cancer tissue.

The challenge is to identify which patients the "targeted" treatment will be most effective. Both genomics and proteomics can identify potential therapeutic targets, but these targets require the determination of cellular endpoints.

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