The following transcript was recorded on 8/28/00 in the virtualtrials.com chatroom!

Musella Welcome Dr. Patel! We can now get started!

Musella The first question, which many people asked:
Dr. Patel: can you explain tumor necrosis therapy, (in a simple to understand way)!

Dr. Patel GBM has necrosis in it, it means dying tumor areas and the treatment involves targeting radiation to these areas

Musella How?

Dr. Patel The radiation is from a radioactive iodine and it is attached to a targeting molecule that has an ability to target tumor so radiation is only given to the tumor

Musella How specific is it for the tumor, compared to normal brain?

Dr. Patel Extremely specific for the tumor in fact, the iodine is attached to antibody that is to only tumor areas

Musella How would this compare with Dr Friedman's trial of Anti-tenascin antibody / I131?

Dr. Patel Tenascin is just another antigen found in tumor our drug targets molecules that are only found in GBM's and certain malignant glioma's our targeted antigen is not found in normal brain tissue

Musella How is the treatment administered? How often?

Dr. Patel The treatment is given directly by infusion into the tumor at present two doses are given. We have done infusion trials into the tumor directly and found this to be safe.

Musella Gary asks: What if any results have we seen or expect to see with cotara?? Is it trying for the cure, to prolong life? Or just to buy time?

Dr. Patel So far results show that this drug is safe to give (Phase I) we are now in Phase II so far we see that there is prolongation of survival even among patients with treated recurrent GBM. Final results are pending.

Musella Nick asks: Is this available off trial? Compasionate use for people with low karnofsky scores? I would add: what are the requirments to get into the trial?

Dr. Patel NO. The drug is not available off trial, Lo K Score patients are not entering into trial (less than 70).

Musella Cyndi asks: Is is possible to become involved in a clinical trial for Tumor Necrosis Therapy if you live outside the United States (ie:Canada)?

Dr. Patel First requirement is tumor size, we would review the MRI and determine size (less than 60 cc's)

Musella When would this trial be done? After surgery and radiaiton?

Dr. Patel Yes, outside US patients have been excepted into the trial
We are accepting patients immediatley after diagnosis, ie, before surgery and radiation

Musella Assuming everything goes well, how long would it take to get FDA approval for something like this?

Dr. Patel I really don't know perhaps a year or so

Musella Can this be done in combination with chemotherapy?

Dr. Patel NO, last chemo has to be given at least 4 weeks prior to treatment

Musella Have you had any individual patients with a complete response yet?

Dr. Patel NO, however we have survivors beyond twelve months who were treated for recurrent GBM

Musella gamble.25 asks: In Techniclone`s web site, there is a statement that `radioactive isotopes have a large killing radius of 100-300 cell layers around the isotope.` For me to better visualize this, what approximate distance is 100-300 cell layers?

Dr. Patel I would guess this to be about half a centimeter

Musella The trial is for high grade gliomas. Will it eventually be used for low grades?

Dr. Patel At present radiation for low grade gliomas is in itself controversial.

Musella ppi8640 asks: Can you compare cotara therapy to the diptheria toxin therapy

Dr. Patel Difficult to compare cotaria with diptheria toxin because Phase II for cotaria is not complete

Musella Ingrid asks: Does the iodine treatment create swelling in the area being treated. Is it limited to certain parts of the brain or can it be applied to the brain stem?

Dr. Patel Treatment would not be done for brain stem lesions. Yes, there is some swelling - easily controlled with steroids.

Musella Why would something like Cotaria be better (theoretically) than stereotactic radiosurgery in delivering radiation to the tumor?

Dr. Patel The antibody targets very specific tumor locations so that this form of therapy is more specific than image guided treatment like radiosurgery.

Musella Are there any bad side effects seen with Cotara so far?

Dr. Patel So far we have seen some side effects related to swelling, however, this has been reveresed with steroids.

Musella AFTER FDA approval, would you see this as a replacement for standard radiation in the treatment of glioblastomas? Or in addition to it?

Dr. Patel I would forsee this as a addition to standard radiation for now, however, results of patients treated initially with cotaria are pending.

Musella Getting off of Cotara for a while... let's switch to general brain tumor questions:
What would you say would be the best treatment plan for a gbm now, using only treatments that are available outside of trials?

Dr. Patel Present treatment should involve biospy or resection (debulking) followed by standard radiation. Chemo is an option.

Musella In general - not including your trial -would a gbm patient do better with "standard" treatments or enrolling in a clinical trial?

Dr. Patel Most patients would do best with standard treatment for now however, some may be candidates for trials like Cotara

Musella Back to Cotara for 1 question: Peter asks: Other than standardized results for the trial, is their any reason why 60cc`s is maximum size?

Dr. Patel We picked this because larger volumes would require larger doses which we felt were not safe.

Musella CashCow asks: Is there a possibility of the FDA granting fast track status for Cotara?

Dr. Patel There is certainly a possibility. We await more results.

Musella GRIFJ asks: When could we expect to see results from Phase II Cotara Brain cancer trails?

Dr. Patel We hope by the end of this year.

Musella Back to general braintumor questions: Do you ever recommend vegitarian diets or life style changes to braintumor patients?

Dr. Patel I do not recommend any specific diets or lifestyle changes for brain tumor patients.

Musella Are you familiar with 06BG? Do you think it is a promising drug in the fight against GBMs?

Dr. Patel I think 06BG may have a role in treatment of GBM, further trials are necessa;ry;

Musella Bud asks: How do you feel about anti-angiogenesis drugs (or a chemotherapy) as a possible prevention step after surgical removal of a AAIII, before any new sign of recurrance is noted?

Dr. Patel I think angiogenesis drugs are useful however, eficacy is still in question.

Musella Can you give your opinion on the usefulness of the following for gbm treatments (one at a time): Temodar

Dr. Patel Temodar is being used , though it is more usefull for AA III

Musella Gliadel Wafers

Dr. Patel Thw wafer are being used though expensive, We await the trial with more concentrated wafers. Still more to be desired even with the wafers

Musella My question: Could Cotera eventually be administered via gliadel wafers (instead of bcnu)? To get a sustained slow release of the drug for a few weeks?

Dr. Patel No, Cotara is an infusional therapy, perhaps in the future it may be given in multiple doses.

Musella High Dose Tamoxifen?

Dr. Patel Initial results were promising it has since been a let down, perhaps in combination with other drugs it may prolong survival, trials underway.

Musella Alternative treatments, like antineoplastons?

Dr. Patel Do not know results with antineoplatons, again this is pending results of Phase II trials.

Musella MEK asks: What is your experience/opinion of the radiation sensitizers like RSR13 and Xcytrin?

Dr. Patel Radiosensitizsers have been tried before and new ones continue in trial, again results are not as expected from results in animal models, however, trials continue with this in various fashions.

Musella Sabrina askes: Are there any trials (or approved treatments) going on outside the USA that looks interesting?

Dr. Patel There are more trials with novel therapies in the US than elsewhere.

Musella manisha asks: is it advisable to administer bcnu to old patients? please weigh the pros&cons of bcnu vs. procarbazine & essaic? are they beneficial in any way without deteriorating the quality of life?

Dr. Patel Quality of Life is of primary importance in these patients, systemic bcnu has sig side effects in many patients. Patient with poor quality of life would not be advised to take bcnu, perhaps procarbazine is better in such a patient

Musella ppi8640 (Davis) asks: Have you an opinion on the utility of Cotara in other highly vascularized solid tumors? Thanks in advance.

Dr. Patel GBM has necrosis in it, it means dying tumor areas and the treatment involves targeting radiation to these areas

Musella GRIFJ asks: In your opinion are phase II results promising enough so far to go into a Phase III?

Dr. Patel We have not accrued enough patients to say one way or the other. There are a few patients with rec GBM who have survived beyond expected life expectancy.

Musella Cyndi asks: Would you recommend this type of treatment (Cotara) to an individual that has completed 7 to 12 rounds of Temodar and shown stable disease or regression. What type of patients are you looking for for the trial..

Dr. Patel Trial entry requires progression of disease (clinical or image) or pts with newly diagnosed GBM/AA.

Musella Peter asks: what treatment, standardized or other (clinical trial--if so, what?), does Dr. Patel recommend for brainstem gliomas?

Dr. Patel Biopsy/resection plus radiaition and chemo depending on pathology.

Musella What type of chemo?

Dr. Patel Chemo depends on the type of histology

Musella Doug asks: Is there an age limit for the trial? (72 year old with a gbm)

Dr. Patel 72 years is acceptable in this Cotara trial

Musella Any news on causation of brain tumors. Cell phones? Nutrasweat? EMFs?

Dr. Patel Cell Phones - No scientific proof, only in association (that means nothing) Nutrasweet, no proof, and EMF's no proof.

Musella Niels asks: Is necrosis a definitive sign of glioblastoma or can there be other reasons for necrosis in a braintumor? Is the percent of necrosis in a brain tumor important for the prognosis?

Dr. Patel Percent of necrosis has no prognostic signifigance. It only means tumor is GBM.

Musella Nick asks: Does the FDA help or hinder your research?

Dr. Patel FDA has not hindered our research, rather funding resources for this less frequent cancer is a problem.

Musella How do you feel about RU-486 for meningiomas?

Dr. Patel RU-486 was promising, however, it has not proven to be as eficacious, I do not use it.

Musella pj asks: Doctor, is a GBM patient who has had a second surgery with chemo wafers implanted whose MRI shows the tumor continuing to grow a good candidate for further radiation therapy, especially your new method?

Dr. Patel The pt with these past treatments may be a candidate depending on size of tumor and clinical status.

Musella What are you thoughts on giving a treatment to a gbm patient AFTER surgery and radiation, but before recurrence, to prevent the recurrence?

Dr. Patel Follow with MRI every 2 months, first sign of progression and the pt may be a candidate at that point.

Musella Is your treatment available to pediatric patients? (5 year old with a recurrent gbm)

Dr. Patel NO, not available at present for ages 15 and under.

Musella PatBeaver asks: Can this type of radiation therapy be used on someone who has already had the "maximum lifetime dose" radiation?

Dr. Patel Yes, because it is targeted radiation and has no effect on surronding areas or the body.

Musella Do you beleive that taking anti-oxidents prevents radiation from working?

Dr. Patel Anti-oxidents should not effect radiaiton.

Musella What`s the best test for distinguishing tumor from necrosis? PET, SPECT, MRSpectroscopy, MRI?

Dr. Patel None of these imaging studies have proven to be superior in distinguishing tumor from necrosis.

Musella We are running out of time.. just 2 more questions....

Musella Cyndi asks: In your experience/history do you see incidence of GBM on the rise as indicated in some published literature. Have you seen increased funding available for research?. And might I add... thank you very much for your time today Dr. Patel. It is much appreciated.

Dr. Patel Funding for GBM Research is not adequate. There is not an increase in it's incidence.

Musella Please detail the Cotara dosage used for the current trial.Will dosage changes be likely for upcoming trials ? Are you aware of dosage comparisons to ongoing China trials ?

Dr. Patel You are welcome
The doses and treatment regimen are not expected to change until we have results from the Phase II Trial, the China trials used different administration methods.

Musella ppi8640 (Davis) asks: Hypothetical, if the Cotara delivery system is your prefered choice, what would be your agent of choice (including I-131)? Is it possible to use other payloads?

Dr. Patel The delivery technique can be used for any drug. As long as it is a targeted drug. Cotara is ahead of the game.

Musella We have run out of time! Thank you Dr. Patel! This trial sounds very interesting and please keep us informaed when you get results!

Dr. Patel Thank you very much for all the questions.....