Individualized Online Clinical Trial Protocol Version 1.0

[gdpawel]

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/chronicdi...?itemID=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%20Pages/TrialHome.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

About the AngioRx Assay in breast cancer:

ER and PR tests in breast cancer, which detect only VEGF expression, or even overexpression, are valuable not because they measure expression of estrogen and progesterone but rather because they detect (and supposedly measure) the ER and PR receptors in the nucleus. The presence of positive IHC staining of such receptors in at least 10% of nuclei implies that the tumor is hormonally dependent and that, therefore, depriving the cells of the hormone will kill them or retards their growth.

Unlike a test for the presence of receptors to a specific antigen, which only "implies" dependence upon that antigen, an AngioRx assay is functional in that it actually assesses the direct or indirect effect of the drug upon the cell, whether it is a tumor cell or an endothelial cell. VEGF just happens to be one molecule which has been implicated in the process but there may be more.

If it were the only protein involved, then one would expect that VEGF expression would correlate with Avastin activity 100% of the time but it actually does so only about 20% of the time. The AngioRx assay doesn't just focus on VEGF or any one protein or mechanism. Whether it's VEGF alone (unlikely) or in combination with other proteins and other mechanical factors, the assay works by assessing the net effect of all those factors.

[Jackie07]

A new form of marketing stragegy? The website states that:

"This is a clinical trial in which the patient will pay for some or all aspects of his or her treatment, which could include surgeries, laboratory tests, expensive anti-cancer drugs, travel (if required), and costs of medical care associated with the treatments. These costs could exceed $100,000. We wish for the patient to be advised that the general topic of patient-sponsored clinical trials has been debated by respected investigators from both sides of the issue and remains controversial."

Please... Don't add more agony to my misery...

[Jackie07]

"Limitations and pitfalls of clinical studies in oncology"
[Article in German]
Onkologie. 2008;31 Suppl 2:67-71. Epub 2008 Apr 18

Cerny T.
Fachbereich Onkologie/Hämatologie, Departement Innere Medizin, Kantonsspital St. Gallen, Schweiz. thomas.cerny@kssg.ch

Nowadays results of clinical studies in oncology are often first found and commented in the news media because of their high relevance to the pharmaceutical market. The limits and pitfalls of clinical studies are manifold and not always appreciated even by specialists as well as journalists and politicians. The planning of a study is a most crucial phase, and most deficits are due to inappropriate design and conduct of a study. Adequate and skilful interpretation of a study is often hampered by many known but mostly overlooked variable pitfalls. Today there is an overrepresentation of pharmaceutically sponsored studies and a painful lack of well-designed academic studies with really meaningful endpoints for patient care. This paper touches several important aspects of today's shortcomings of clinical studies in oncology and highlights the importance of strengthening the academic clinical research. Evidence-based medicine needs to be more clinically relevant, and therefore we need well-designed, and critically interpreted studies in the future. Copyright 2008 S. Karger AG, Basel.

[gdpawel]

The very new test, called the Microvessel Vascular (MVV) assay for detecting drug-mediated death of tumor infiltrating endothelial cells is not being marketed 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.

The most immediate application of the MVV assay focuses upon cancer and specifically upon a much-heraled new class of agents called angiogenesis-inhibiting drugs, which work by attacking tumor vasculature and thereby starving cancer cells. One problem with these drugs, in addition to their high cost, is determining in advance who will benefit from them. The other problem is learning how to make the drugs more effective by using them in combination. The new MVV test could help on both fronts.

The test works by measuring drug effects upon endothelial cells which make up blood vessels. Its use could prolong lives, save money, and spare patients exposure to harmful side-effects of ineffective chemotherapy treatments. The effects of various drugs upon endothelial cells can be measured separately from the effects of those same drugs upon cancer cells within the same biopsly specimen.

No one is publishing "real world" studies except laboratories performing cell culture-based tests, which can only do "real world" studies, because their studies require fresh, viable tissue, which must be accessioned and tested in "real time" under "real world" conditions.

Fortunately, receptive people are not so threatened by ideas which dare to challenge and question one-size-fits-all, widgets-on-an-assembly-line medicine. It's certainly not more comforting to see patient after patient succumb, not to the cancer, but to an early demise thanks to wrong-therapy/wrong-dose cookie-cutter treatment.

There are limitations involved with randomized clinical trials. Perhaps the greatest limitation is that it is predictive of population trends, and is not definitive. Clinical trials provide few black and white answers. The problem with the empirical approach is it yields information about how large populations are likely to respond to a treatment. Doctors don't treat populations, they treat individual patients.

Because of this, doctors give treatments knowing full well that only a certain percentage of patients will receive a benefit from any given medicine. They subject patients to one combination chemotherapy after another, just going from one journal paper to another journal paper. They need information about the characteristics that predict which patients are more likely to respond well. The empirical approach doesn't tell doctors how to personalize their care to individual patients.

Source: J Intern Med 2008; 264: 275–287.

[Jackie07]

I am having difficulty locating the article with the citation: Journal of Internal Medicine, Volume 64, Pages 275-287. Is it a pre-prepublication? PubMed database lists prepublicated articles but returned zero result when I searched by the citation. The wording does not sound like one from a scholarly journal. There's no matching citation by the key words, either. Is it a 'future' 'letter to the editor'? Who is the author?

[gdpawel]

Here's your "Platter"

http://www.blackwellpublishing.com/j...54-6820&site=1

Click on View content online

Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood

[Jackie07]

Found it!

I wonder if the Weisenthal Group can get a grant from the government or financial backing from pioneers such as Craig Venter to conduct the phase II trial. Most clinical trials seems to be offered free to selected individuals.

But seems I remember some time ago I had located one research article on the particular method used here. I believe it reported a benefit of averaging 3 1/2 months surviving time. (7 months verses 3 1/2 months)

The Weisenthal Group ought to start a media campaign to draw attention and get needed funding and recruits.



Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood
L. M. Weisenthal, N. Patel & C. Rueff-Weisenthal From the Weisenthal Cancer Group, Huntington Beach, CA, USA
Correspondence to Larry M. Weisenthal, Weisenthal Cancer Group, Huntington Beach, CA 92647, USA.
(fax: +714 596 2110; e-mail: mail@weisenthal.org).

Copyright © 2008 Blackwell Publishing Ltd

KEYWORDS
angiogenesis • cancer • cancer chemotherapy • cell biology • endothelial cells • oncology

Weisenthal LM, Patel N, Rueff-Weisenthal C (Weisenthal Cancer Group, Huntington Beach, CA, USA). Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood. J Intern Med 2008; 264: 275–287.

ABSTRACT


Abstract. Background. Angiogenesis studies are limited by the clinical relevance of laboratory model systems. We developed a new method for measuring dead microvascular (MV) cells in clinical tissue, fluid and blood specimens, and applied this system to make several potentially novel observations relating to cancer pharmacology.
Methods. Dead MV cells tend to have a hyperchromatic, refractile quality, further enhanced during the process of staining with Fast Green and counterstaining with either haematoxylin–eosin or Wright–Giemsa. We used this system to quantify the relative degree of direct antitumour versus anti-MV effects of cisplatin, erlotinib, imatinib, sorafenib, sunitinib, gefitinib and bevacizumab.
Results. Bevacizumab had striking anti-MV effects and minimal antitumour effects; cisplatin had striking antitumour effects and minimal anti-MV effects. The `nib' drugs had mixed antitumour and anti-MV effects. Anti-MV effects of erlotinib and gefitinib were equal to those of sunitinib and sorafenib. There was no detectable VEGF in culture medium without cells; tumour cells secreted copious VEGF, reduced to undetectable levels by bevacizumab, greatly reduced by cytotoxic levels of cisplatin + anguidine, and variably reduced by DMSO and/or ethanol. We observed anti-MV additivity between bevacizumab and other drugs on an individual patient basis. Peripheral blood specimens had numerous MV cells which were strikingly visualized for quantification with public domain image analysis software using bevacizumab essentially as an imaging reagent.
Conclusions. This system could be adapted for simple, inexpensive and sensitive/specific detection of tissue and circulating MV cells in a variety of neoplastic and non-neoplastic conditions, and for drug development and individualized cancer treatment.

[gdpawel]

No investor is going to pay for a 3 million dollar phase II or III trial, particularly when there are 800 pharmaceutical in the clinical trials pipeline and there are not enough clinical trial patients to go around.

The methodology of the assays is particularly stringent in that three different cell-death endpoints evaluate the activity of various drugs (up to 30) against the tumor (thus mostly the high cost).

If a laboratory were to perform both IHC and RLB endpoints on each specimen, the overall reliability of the end result would be greatly improved. But the standards of cell culture assays are particularly high.

I personally had thought about Craig Venter and wrote to him. Some have suggested PatientsLikeMe. I had initiated contact with James Heywood. Also Jay M. Tenenbaum of CollabRX.

[gdpawel]

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.

[Jackie07]

We need to get some rich people like Warren Buffett and Bill Gates involved. Anybody knows how to start a foundation for Her2 research?