Roll Call: Anyone in the Phase III Trial of Bisphosphonates

kt57

I just got a packet from the clincal trial nurse -- it looks like they are increasing the number of people involved in the study and that they want more blood to test for side effects form the drug.    Anybody else get this info and have to sign a new consent form?

unklezwifeonty

Dear Laura,

Your onco is right that it is not standard of care other than for bone density. The question of whether it should be made the standard of care is exactly the question that the trial is expected to answer.

I'm in the same boat as you - my onco is not participating.  But new centers are being added each week and they may change the end date also. I'll be asking my onco on Monday and will update you after that.

azdiva

Great, Onty!

I was thinking of playing the cancer card . . . but I don't think it will work with him!!  haha

Have a great day!

Laura 

unklezwifeonty

Dear Laura,

Nice try but she probably gets shown that card 100 times a day :-)

Morgan513

I was premenopausal before chemo and now, of course, I am menopausal.  Onty is exactly right about the purpose of the trial.  It seems that early data coming out of the trial indicates that bisphosphonates actually help bone mets and other types of mets as well.

I only received the letter increasing the wait time to 60 minutes before eating and drinking.  I wonder if I'll get another letter.

Lorrie 

weety

There is another thread about this trial called "Zometa" under the Stage III forum.  A lot of women have gotten their doctors to prescribe zometa as a precautionary against osteoporosis, although the protocol for that is less often--only once every 6 months.  Some of the women have even paid for it themselves.  I don't remember exactly, but I think the cost was about $1000 for the year--not too terribly expensive if it would keep the mets away!

I live in an area where there is a center participating, but I called on Wednesday and have not had a return phone call yet.  I wonder if that is a bad sign.  I am also going to ask my onc about going the osteoporosis route, and see what she says.   I guess it can't hurt to ask!

unklezwifeonty

Clinicaltrials.gov website says that the expected completion date is Dec 1, 2009. Does anyone know if that is still accurate?



By the way, I asked my onco last week. She could give me bisphosphonates and would recommend it after the AC part of my chemo. She is not participating in the trial. But I'm hopeful she will be able to justify it with my insurance.

weety

Well, I just got a return call from the coordinator of the trial.  Apparently, not all insurances are covered.  The study only pays for the actual drug, and for the other costs (administration of medications, labs, office visits, etc.) they don't accept HMO.  I tried to get her to explain if it is the HMO's that don't pay or if it is that the study won't work with the HMO's but she didn't seem to have any answers.  So, I'm out of luck I guess on the study.  She did mention that I could pay out of pocket, but even with the drug cost covered, I'm sure it is still too expensive to go that route. 

Unclezwifeonty, I think the study will be open beyond the Dec date.  SHe said they are looking to enroll over 5000 patients and don't have that number yet.  Only the boniva arm has been closed.  THe other 2 arms are still recruiting.  I don't know why one arm would close early--I thought it was randomized which would have made equal groups--but she didn't know the answer either. 

unklezwifeonty

Dear Weety,

That sucks. I'm guessing if we ask the onco to prescribe a bisphosphonate off-trial the insurance would only cover the dose needed to help with osteoporosis.

By the way, I had heard that the boniva arm would be closed because of "supply issues" (meaning that big pharma does not want to pay for boniva).

bluedasher

Onty, the dosage of Boniva for the trial is a lot higher than the dosage for osteoporosis. (50 mg once a day vs 150 mg once a month - about 10x.) They may actually be having trouble keeping up with supply. On the Clodronate arm, there have been shortages at times.

Weety, It must be a matter of what Southern California Kaiser is willing to cover with their HMO. I'm in Northern California on Kaiser HMO and they covered the trial.

unklezwifeonty

Thanks Blue. How did they arrive at 10x the dose? My understanding is that they chanced upon the benefit to BC when they found that ladies who were getting bisphosphonates for osteo did better on DFS than those who were not. So even the lower dose should work...... no?

azdiva

Onty - 

You're right.  I think even the lower dose is helpful.  The Australia trial is doing Zometa every 6 months and they have shown good result.

I think the researchers would all agree that it is useful.  They are trying to find most effective drug and at what dosage.

Which is why I want to be on it, but Onc says No!  We shall see.  I am wearing him down!

How are you feeling today?

Laura 

unklezwifeonty

Dear Laura,

I'm doing much better with AC #3. I think with AC #2 I neglected to drink lots of water and that caused a lot of issues.

TexasRose

My clinical trial nurse had given me a copy of the trial papers to look over and see if I wanted to participate. When I went back to sign the papers for the study, she had a new set of papers because the ibandronate arm had closed. These papers say that the ibandronate arm was limited to 1400 patients while the Zometa and clodronate arm were recruiting 2000 patients each.

My insurance is an HMO and they are paying for everything connected to the trial.

unklezwifeonty

Thanks for the info Mary....

bluedasher

Onty, they are using the dose that they have been having success using with women who already had bone mets which is much higher than the dose they use for osteoporosis.

I don't know why they tried it for mets. 

unklezwifeonty

Dear BlueDasher,

Thanks for the info. Theoretically it makes sense to use bisphosphonates. I am not convinced that such high doses are good for the patients. They are good for the drug companies for sure :-)

Love,

bluedasher

Onty, I can look at it two ways:
The very cynical view is they run drug trials with high dosages to get lots of money for lots of drugs when the trial is done.

The less cynical view is that they want to run the drug trial with the highest dose that they believe has a reasonable safety profile in order to give the drug the best chance of succeeding. With an adjuvant cancer drug, it is usually going to take 2 to 4 or even more years to know if it is reducing recurrence. If they ran the drug trial with a minimal dose and the dose isn't effective, was it because the drug won't help at all or because the dose was too low? Do they raise the dose and start a new trial? Another 2 to 4 years before the drug company can sell the drug for that use, another 2 to 4 years before most patients can benefit from it and the women in the first trial got little or no benefit from taking the drug.

So they run the early Herceptin trials giving the drug for a year or the bisphosphonate trial using 3 years of drug levels that helped women with mets - dosage levels where it either helps or a significantly higher dose would be too much risk or too onerous to be worth trying. Once they know that the drug is effective, there could be further trials to see if a lower dose helps (usually not funded by the drug company :^( but there are others like governments who pay for health care may pay for, e.g. FinHer).

To some extent, the high dosages in trials are kind of hard for the drug companies too. One problem for Genetech in getting the Herceptin drug trials going was the amount of their production capacity that the drug trial would take - a lot of expense and lost opportunity cost (because they could use that capacity to test other drugs) if the drug trial finds the drug isn't effective. Apparently the amount of drug needed for this trial is a struggle for the manufacturers of the ibandronate and clodronate too.

weety

Bluedasher, So interesting that you would say that about the high levels of drugs in clinical trials.  That is EXACTLY what my onc told me when I was first considering joining the BETH trial with avastin.  She told me that the problem with trials, is that the dosages are usually extremely high, usually too high, and there is no room to play around with the amounts like you can once it is approved for standard care.  You have to go with the protocol established if you want to take part.  The drug companies don't want to take a chance of the drug not succeeding (because of $$$$ and time) so they give the highest dosages possible that were found to have acceptable toxicities in the phase I and II studies.  I was already completely sold on the BETH trial  (I saw it as a sign that the trial was called BETH because that was my mom's name and we lost her to uterine sarcoma a few years ago!)  but my onc really talked me out of it.  She was really concerned that the toxicity might be hard to manage/overkill for early stage breast cancer patients.  She recommended going with the TCH chemo that has a great track record already and leave Avastin alone. AND my Kaiser was a study site for this trial, so I found it kind of odd that she was steering me away from it. 

So I guess that it is really important to keep this kind of info in mind when trying to decide whether or not to enter clinical trials.  I'm glad you brought it up and pointed this out to all of us!

unklezwifeonty

Dear BlueDasher,

Your explanation makes sense.

weety

Well, I asked my oncologist Friday about the zometa trial.  I also asked her if it  would be an option to prescribe it off-label for prevention of osteoporosis.  She looked at me like I was crazy when I asked this.  She said "No one would prescribe this for osteoporosis.  Everyone is afraid of the osteonecrosis side effect.  It's just for mets and it works wonders for that."  I felt like saying, "Lady, there are a ton of doctors prescribiing it for osteoporosis--just go to breastcancer.org!"    But I was already tired of pressing the issue.  I'm already at a high risk of osteoporosis because of my small size and frame--I'm 5'2" and just barely 100 pounds.  I think i'm going to have to refocus myself and go back in there at my next appt and give her the data and stand firmer ground.  I'm not one to keep pushing.  Anyone got any good data to share to help with my case?

Lindissima

Hi weety,

My oncologist prescribed Zometa for me for prevention of mets AND osteoporosis. They fought for the insurance to cover it for me.  I have studies I can email to you if you send me your email address via pm.  Here are some links for starters.

Bone Drug Zometa Prevents Breast Cancer Return on RxList

Medical News: ASCO: Adjuvant Bisphosphonate Shows Potential Breast Cancer Benefit - in Meeting Coverage, ASCO from MedPage Today

Zometa Reduces Risk of Breast Cancer Recurrence in Premenopausal Women, Study in The New England Journal of Medicine Reports - Drugs.com MedNews

Zometa Reduces Risk of Breast Cancer Recurrence in Premenopausal Women, Study in The New England Journal of Medicine Reports - Drugs.com MedNews

There is a nasty side effect to consider: osteonecrosis of the jaw.  I was told it was very rare.

Good luck. (PS: Hope these links work!

unklezwifeonty

Dear Weety,

1. Dose of bisphosphonates for BC is 10 times that for Osteoporosis. The doctors would very likely not prescribe them to you at the levels recommended in the BC trial. The advantage of participating in the trial is that you get monitored more frequently for bone mets. With close to 400 centers participating in this trial, you will most likely find a doctor near you that's participating. But if you choose to not participate in the trial, the drugs are not that expensive and relatively safe enough that you could get them in grey market (shipped from Canada) for $200 a month or so. The risk of Osteo Necrosis of Jaw (ONJ) is less than 0.5%. A dental checkup and clearance from the dentist before starting the treatment would reduce that risk even further.

2. A German clinical trial of clodronate vs placebo indicates significant improvement in DFS @ 3 years and 4.5 years but not at 8.5 years. The OS was significantly improved at 8.5 years. See http://annonc.oxfordjournals.org/cgi/content/abstract/19/12/2007. The last line in the publication under the "results" heading can be misleading until you look deeper into the data.

3. A Korean clinical trial of Zometa vs placebo in patients with metastatic disease indicates that compared to ER/PR+ patients, the ER/PR- patients benefit much more and have significant improvement in OS from bisphosphonates. See http://www.biomedcentral.com/1471-2407/9/154.

4. A Finnish lab study in mice (not humans!) showed significant improvement when Zometa was given the day after Adriamycin. But in that study, both Zometa and Adriamycin were given at much higher doses than given for BC. See http://clincancerres.aacrjournals.org/content/14/14/4658.short.

5. I asked my onco last week and she said she would recommend this trial. The hospital's research nurse emailed us yesterday and indicated that they are accruing for the trial (SWOG 0307).

Good luck and keep us posted on what you decide. I will most likely enroll and start the bisphosphonates treatment sometime during the Taxol + Avastin/Placebo part of the chemo.

unklezwifeonty

See this thread http://community.breastcancer.org/forum/67/topic/724607

Morgan513

So Onty, are you going to do it?  

Lorrie 

unklezwifeonty

I want to.

Warrior517

I am pre menopausal and I receive Boniva! I believe it is for both pre and post. Granted, when I started it, I had been in chemo menopause but things changed six months later. My cycles are back every 28 days on the nose! I was 39 at diagnosis last year.  Somewhere in the gray zone between pre and post

Morgan513

Onty--

Keep me posted and let me know if you participate.

Take care,

Lorrie 

unklezwifeonty

Dear Lorrie,

Will do. My onco had recommended that we discuss the start of bisphosphonates after I finish AC so I am guessing I will bring it up at my next visit.

Morgan513

Oh I hope you do it.  There isn't much for us TripleNegs and I feel like this can really help.  I hope your treatment is going well!

Where do you live in NJ?

Lorrie