'K' from USA - Dx 2007 at 10 years old

[Fictional]

I probably shouldn't post yet because I don't know what SARC will decide to do, but I am restless and there's nothing I can do through the weekend anyway. We got what we thought was a great scan yesterday.

A big nice surprise - her largest tumor shrunk by 30%. This is very nice. There were 3 'index' mets that were 1 cm or larger at the beginning of the study - now 2 have gotten smaller - but the 3rd has grown 2mm over 6 months. We don't think that's all that bad - and in fact, the ones that shrunk were the largest ones. The rest are small and unchanged. No new ones.

But here's the rub. The R1507 study uses WHO criteria - so even though all the total tumor burden is lower than at the start of the study 6 months ago (if you add up all the diameters of measurable lesions), because 1 lesion has grown - and depending on the radiologist used... 28% or 20%, she is in danger of being kicked out of the study. If even a single nodule grows more than 25%, supposedly that is 'progressive disease'.

So we don't know. The oncologist is on our side, he thinks the medications really helping. We have to wait until the coming week to see if we can continue on the study. Because different radiologists measure each time, there are commonly 1-2 mm differences in what a radiologist called the diameter on a particular day.

Also don't know if you've been following the R1507 posts, but Roche pulled out of the R1507 study because it was told to get rid of 1/3 of its clinical trials before merging with Genentech. There is some concern that R1507 may be dropped. I hope it is encouraging though, at the NCI, 'K''s trial (R011) is still accruing patients and I saw that they added a Genentech email address for more information about the trial. R1507 may be especially important for peds sarcomas (for instance peds GISTs have 10x the level of IGFR of adult Gists). We would like to be on this drug for a long time if we can - the infusion is a little bit of a pain (but she has a portacath) - but best part is much more energy (full time school, sports) and few if any side effects compared to other drugs.

The clinical trials business is totally not set up for ASPS...multiple lesions, slower growing.

[Bonni Hess]

Dear 'F',
Thank you for channeling your understandable restlessness to update. It is wonderful and very encouraging that two of 'K''s largest index mets have shown significant shrinkage, and that she continues to have no new mets. I am sorry that there appears to be some increased growth in the third large index met which could jeopordize 'K''s participation in the Trial, and I know how very difficult the nervous waiting for a decision about her eligibility to continue is for all of you. 2 mm of growth of one met during the past six months is certainly very minimal, and it surely could be attributable to CT scan variation or radiologist error. Hopefully this will be taken into consideration by whoever is responsible for determining 'K''s continued Trial eligibility, and she will be allowed to continue on this promising treatment which has been effective in shrinking two of her largest lung mets, and preventing the growth of any new ones. 'K''s overall apparent successful response to the drug with only minimal questionable increased growth of one lung met, combined with the comparatively minimal side effects which she has experienced, seems to be a very valid argument for her remaining on the Trial. If that is unfortunately deemed not possible due to rigid WHO criteria, perhaps she could continue on the medication on a compassionate use basis. Know that my positive thoughts and best wishes are with 'K' and your family, and please let the Board know the outcome of the study decision which will Hopefully be made early as opposed to later in the coming week.
With special caring thoughts and continued Hope,
Bonni

[Amanda]

Hello 'F',
The scans do sound very darn good and hold onto that!

I would hope that they would not take her off the drug over such a small mm change and as you and Bonnie and * everyone * knows this mm is not a valid reason to remove her from the trial. Also if this drug is working on others dont they have a moral and liable reason that makes them have to continue the paitents if there is positive results?

You are all in my prayers and thoughts and please post back tomorrow when you hear from them.

In healing hopes for all!
Amanda

[Fictional]

Thanks, Gals.

We were able to get our infusion today like usual. Hooray! Our onc (Suman Malempati, a sweetie) was a comforting presence - he told us they will review scans at OHSU and will have to notify SARC, and then figure out where to go from there. He fairly optimistic thought it would be appropriate to keep her on study, but would try a back-up of compassionate use if we're kicked out. He was approving the next several weeks on R1507.

By RECIST criteria, total tumor load is decreased 18% (stable disease) from July - darn good we think too considering she was actively progressing at all sites after metronomic. And we find it incredibly encouraging that the largest 2 out of 3 'target' lesions were the ones that shrunk (we're hoping for #3).

Will keep you posted. : )

[Bonni Hess]

That is very good and encouraging news 'F'! It is wonderful that the Trial oncologist is so supportive and that he is willing to work together with you to keep 'K' on the Trial, or at least on the medication on a compassionate use basis if it is determined she is no longer eligible to continue on the Study. Hopefully her next scans will show continued stabilization and increased shrinkage which will negate the concern and risk of her being taken off of the Trial. Take care.
With special caring thoughts and continued Hope,
Bonni

[Fictional]

Hi everybody,

We're doing pretty good, but 'K' will be coming off R1507. Too bad - she's been on R1507 for 9 months. We would really like to be on it (or a similar drug) at some point in the future, but we'll have to cross that road when we come to it.

We are still about 10% down by RECIST for the 3 largest nodules that they were following, but according to the study protocol if anything gets larger than 25%, then you're kicked out of the study. There's one nodule on the left that has been chugging along at a slow rate (1 mm every 2 months or so) and that's the one that makes us leave the study. Without a doubt, though R1507 has been good for 'K'. There's another met on the left that's also grown on the right (still under 1 cm I think), but everything else (maybe 90%?) are like they were in a deep freeze... Most of these were 2-7 mm range. In the best of all possible worlds we would like to alternate between IGF and met inhibitors and see what that would do. The side effects just seem so low on those drugs - and we think they may be better at inhibiting new metastases than VEGF inhibitors, especially at 'K''s stage (2-3 yrs out from her primary being removed).

So we're waiting to see what to do. There is that largish one on the left - but we think it is not such a dangerous area. We sent films to Rolle about 2 weeks ago (but the holiday) and haven't heard what he has to say yet.

We are thinking about going on another met inhibitor (PF02341066 or something like that) if we can get into the trial from Seattle. We also consider VEGF inhibitors- but if we can postpone that, it would be easier for sports (volleyball), fatigue, etc.
She got to go to Las Vegas with the Sunshine Kids - they had a teens with cancer trip and she had a great time... Lance Burton magician, rollercoaster, Blue Men, but the best part was making friends - even a close friend who she's been texting since she's gotten back.

[Bonni Hess]

Dear 'F',
I am so very sorry about 'K''s lung met growth which has resulted in her no longer being able to participate in the R1507 Clinical Trial. I was so very Hopeful that the R1507 would be a successful treatment for her, and I share your great disappointment about the mixed results outcome of her nine month treatment with this new drug which seemed to be so promising and which you were so encouraged about. Regarding your consideration of possibly trying another C-met inhibitor, do you have any data regarding successful C-met inhibitor treatment results for ASPS patients? At least in the case of the C-met inhibitor ARQ-197, the only ASPS patient who I personally know of who has experienced some apparent treatment success is Cindy's son. Despite some of the adverse side effects, it seems that Cediranib might be worth considering based on the significant successful Cediranib responses thus far of several of our ASPS Community patients who are being treated with this promising new medication. I was contacted yesterday by a newly diagnosed ASPS patient who was just accepted into the NIH Cediranib Clinical Trial, and is scheduled to begin treatment in early May. She said that she is the last patient to be accepted into the Trial. so I don't know whether or not if that means that the Trial is now closed to further enrollment. I have encouraged her to submit an entry on this Board, and to update about her Cediranib experience and results, so Hopefully she will do so. I am so happy that 'K' was able to enjoy a fun trip to Las Vegas with the Sunshine Kids organization and that she was able to meet some new friends who truly understand what she is going through and feeling as a young girl with cancer. My continued special thoughts and best wishes are with her and your family, and I will look forward to your next update when you decide which treatment plan you will be pursuing. In the meantime, please take care, give 'K' a hug from me, and enjoy today's beautiful Seattle Springtime sunshine.
With special caring and continued Hope,
Bonni

[Fictional]

I don't think that I have any additional knowledge of patients. The decision is a complex one and I'm not sure its easy to explain in bulletin board posts. But here's a little of our thinking...

Our greatest concern in the first few years in 'K''s case has been wanting to avoid new mets. Her primary was quite large (probably > 5 cm) which put her at risk for disseminated metastases - as you know new ones can show up for a long time, but it seems the worst in the first few years after the primary is removed. From the molecular perspective, knowing how different molecules work, there is a suggestion that met inhibitors and IGFR inhibitors would be more effective at inhibiting new metastases than VEGF inhibitors which could be better for killing off tumors once they are dependent on an enriched vascular supply. The last time we know for sure there was a new lung met for Kgal was probably about 2 years ago - and for that we are very grateful. She has only 1 larger nodule on the left - and it is (we don't think) in a bad location. Rolle still hasn't answered - we're going to call him this week (maybe the holiday). The other ones haven't grown in 9 months and are still tiny, so (again we don't know -we'll have to see what it does off meds) we're very happy with this.

For some of the long survivors with ASPS, it seemed as if most of the lung ones went dormant, then if 1 or 2 tumors kept growing, then they might have to go to surgery. We recognize surgery is quite a deal, but can't ignore that many of the 10-15 year plus survivors had repeated lung surgeries to become stable. If she needs to do it, we will do it. She's 2 years + out from surgery on the right and 1+ year out on the left. The one that is the biggest is one that Rolle missed with his surgery 1 year ago - it was a difficult surgery because she had had a conventional thoracotomy on that side in 2007.

We also had profiling results which suggested that the small mets were negative for VEGF and PDGF, and anecdotal evidence that ASPS patients on cediranib with smaller tumors tended to have less shrinkage and less effect. I guess are feeling is that if things progress more for 'K', then that might be a better time to go on the drug.

We also care about quality of life issues - and factor our daughter's temperament into it. In sports she has gotten hit in the head with a ball several times, and we could not let her do sports if she were on cediranib. I think the kids trial for cediranib is still open and opening at more sites, but we're not there yet we think. I also confess to being a bit spooked by the rebound effect of VEGF inhibitors...realizing that she came off Sutent before... she also lived through a Sutent stoppage that coincided with development of new metastases and growth of small lung mets.

Also although you may not have thought ARQ197 was successful, we saw that once she began it, she no longer had new metastases (still true today) - and both times we went to surgery, she had a few necrotic nodules (40-80% cell death) that must have been due to the ARQ197. They killed the most rapidly dividing nodules too - would be great if a little more met could kill off the stem cells in that lung met on the left that is still chugging along.

Finally, I think our goal is evolving more to just trying to keep ASPS in her lungs if possible and keep them dormant. I used to think we needed to get rid of all the tumors, but now with all the data out on cancer stem cells and hearing about stable ASPS patients who have "dormant tumors everywhere", I think our goal is just dormancy. Dormancy may be killing off the stem cells (the cells that continue to differentiate and grow...in some solid tumors they make up only 10-20% of a tumor).

PF02341066 looks like a pretty well tolerated oral drug too - and it might be more effective than ARQ197 because it blocks a slightly different site. No way to know unless we try. Apparently Seattle Childrens is approved for the study - and the drug has already been tried in adult patients (1 sarcoma PR, not ASPS though) and seen to have fairly mild side effects, no immunosuppression, really looked a lot like ARQ.

Anyway hope that makes sense. I don't know if we're wrong about this - but it seemed the best decision for the present and we are thankful that her scans are as good as they are. : )

[Bonni Hess]

Hello again 'F',
Thank you for your very informative response regarding the basis and rationale for your decision about C-met versus VEGF treatment for 'K'. Certainly the treatment decision must be based on the individual factors which you cited, and which you have so well evaluated. My basis for concern about C-met inhibitors is the increased tumor growth which Brittany, Adam, and Mario all experienced within a short time period ( less than three months) while on the ARQ-197. Also, at the conclusion of Brittany's participation in the ARQ-197 Trial when her lung met growth exceeded the allowable 20% and she was no longer eligible to continue on the ARQ-197 Trial, we asked her Clinical Trial oncologist how many patients in the Trial nationwide had experienced a successful response to the treatment, and he told us there had been one patient out of twenty six at that time, which certainly didn't seem to be very encouraging to us. However, it seems that 'K''s ARQ long term treatment results were better in terms of possibly preventing the development of new mets, so she does seem to have benefited from the treatment, unlike Brittany. With this unpredictable disease it is always difficult to determine if stabilization of the disease and necrosis of tumors is the result of treatment, or just the nature of the disease itself as we experienced with Brittany during about a two year time period when inexplicably all but five of her over fifty lung mets disappeared and she had no new mets despite not having undergone any kind of treatment except for the resection of her primary tumor and radiation to the primary tumor site. For Brittany, the Cediranib VEGF treatment has definitely been more successful than the C-met since with the Cediranib she has thankfully had stable disease with no new tumors for almost a year, and has had significant shrinkage and disappearance of both large and small mets, which seems in conflict with the anecdotal information which you cited "that ASPS patients on cediranib with smaller tumors tended to have less shrinkage and less effect". Of course, this is once again an indivdual experience. We all have to make the best treatment decision we can based on the totality of the individual personal situation and needs, and the treatment that seems to offer the best chance of success and outcome based on those factors. My very best wishes are with 'K' and your family for a very successful outcome to whatever treatment she undergoes, and I will continue to follow her courageous journey with special caring and great Hope. Take care dear 'F' and know how deeply grateful I am for all of your graciously shared knowledge and invaluable information.
With special caring thoughts and continued Hope,
Bonni

[Fictional]

Hi again everybody,

'K' was able to enter the PF02341066 study a few days ago. It's another oral met inhibitor. More GI stuff than Sutent or ARQ197 the first day - but when she takes a Zofran and Lomotil, she says she's fine. From other patients on the drug, they said these GI symptoms are worst in the beginning. This drug has attracted a lot of attention in the news because it has dramatic effects in tumors with Alk mutations - but ASPS does not have this mutation. We don't know if it will work in ASPS. But it does seem as if its a fairly potent met inhibitor, and we were glad to get into a study so quickly. 'K''s primary and lung mets are positive for met, although after ARQ, the met levels had dropped to 1+ in 80% cells instead of 3+ in 100%.

We also heard back from Rolle - his email got sent into my trash file. He suggested we consider RFA...so here we are at these difficult questions again. He thinks it may be accessible by RFA - and because of the prior lung surgeries, he thinks the chances of pneumothorax are low. He didn't say no to surgery, but he said he worried that with the resection of this nodule and other small nodules nearby, there would be a risk of lobectomy - and that would cause significant disability. Ugg. So more tough decisions. The tumor is otherwise not in a very dangerous place and is growing slowly (1mm every 2 months) - so we have a chance to try some other drugs and think through our next steps.

Things we are considering - RFA + this met inhibitor. Apparently surgery is not permitted in the first 4 weeks, but after it is fine. Since c-met is highly implicated in the development of new metastases, this may be as good an opportunity as any to do RFA. Our main concern with RFA is causing extrapulmonary metastases. I didn't realize it would be possible to stay on a clinical trial and have surgery / RFA in the middle - maybe because it is phase I?

Other things to consider - a trial in Los Angeles caught our eye - Sutent + CP-751,871 (another IGFR Ab) - it is only for adults, but we were at Premiere Oncology before and got the ARQ197 there by asking for an age waiver.

Cediranib - but now closed to kids - and maybe the adult study also closed now too?

Misc VEGF inhibitors - pazopanib, afinitor, sutent.

'F'

[Amanda]

Hello 'F',
I am so glad you were able to get her into a trial and that the tumor is growing so slow!
from what i have been told and read RFA seems to also be a faster heaing time and less scarring of the lungs.
I am sorry you are facing such tuff decisions right now! 'K' and your family are in are thouhts and prayers for healing and streangth!
I wish i could do more! I am in Los Angeles and if there is any thing i can do on my end of the map to help you with this let me know!

[Karen Imm]

Hi 'F',
Such difficult decisions to make. Even with lots of information, it is difficult to know what the best route will be. Please know that you and your family continue to be in my thoughts and prayers as you make these decisions. As always, I admire your tenacity and fight for the health of your daughter. Thinking of you.
God bless,
Karen Imm

[Bonni Hess]

Dear 'F',
I'm sorry to be slow in responding to your thoughtful update, but I was having difficulty logging onto the Board for the past two days. I am glad that 'K' has been able to start the PF02341066 Trial, and my very best wishes and greatest Hope are with her for a very successful response to the treatment. Hopefully the PF02341066 will stabilize the progression of her disease and shrink/destroy her lung mets so that you will not need to pursue any of the other treatment options which you discussed. Regarding possible RFA treatment for 'K''s lung mets, based on Brittany's experience with both RFA and Cryoablation of her lung mets, I would like to encourage you to at least consider and explore Cryo with Dr. Peter Littrup at the Karmanos Cancer Institute in Detroit as an alternative to RFA. Although both procedures were thankfully successful in killing Brittany's treated lung mets, we have always suspected that her lung RFA may have caused further metastasis, and also she experienced a pneumothorax during the RFA procedure and one following the RFA, whereas this didn't occur with either of her two Cryoablations. However, RFA certainly was a very good treatment option with a very successful outcome for both Brittany's liver met and her tibia met. I know far too well how very difficult these treatment decisions are, but I am grateful that you are able to make well informed decisions that best meet 'K''s indivdual situation based on your extensive medical knowledge and research about the various treatment options. I Hope that 'K''s PF02341066 related GI problems resolve quickly, and that she wil tolerate the treatment well with minimal negative side effects. Please give her a special hug from me, and know that she and your family are in my continued most caring thoughts.
With special caring and continued Hope,
Bonni

[Fictional]

Really appreciate your replies everybody. Bonni - thanks for the reminder about Cryo. Yes this is something to consider - and especially since not only did the local tumors not go away, but no new events were seen afterwards. Encouraging.

I sent an email to Littrup to see whether he would even consider - and we could send a CD of films.

I saw that like RFA, Cryo is limited to under 3 cm.

When we tried to get into Karmanos clinical trials last year, we couldn't because 'K' was a child. Hopefully that won't present a problem. He has an appointment also at Wayne state and does Peds rads interventional there, but I don't know whether the cryo thing is available there.

We would like to get rid of her 'big' one if we can. There are a few on the right that are 1 cm, so she is still eligible for clinical trials.

I was reading about RFA and how they are less successful for deeper lesions because of the heat sink effect of the great vessels. It is central and I don't know if accessible by Cryo probe - if too close to the great vessels etc. I would think it is not so bad, but don't know their margin of concern. Very difficult business. Will let you know.

GI effects have improved with a standing dose of Zofran and Imodium with the pills - that is great. She is light sensitive (had been before - has migraine) and is having some of the visual side effects associated with the drug - pretty weird - moving edges of objects - but was fine to go to school, still able to study for school tests and joke around.

[Fictional]

Hi everybody,

Scans today and thankfully everything is rock stable. This may not seem like much because last scans were 4 weeks ago, but there was slight in growth in a few of the largest tumors in the 3 weeks we had to be off everything in-between R1507 and PF02341066 (we told them R1507 was working!).

Regardless. At least now there is absolutely no budge. Even that rotten one that kept chugging along didn't do a thing. And some of the ones that shrunk a bit on R1507 look like they're getting a little more shrunken. Next scans 2 months.

We are asking if we can do cryoablation of the left and still stay on trial, but oncologist thought probably not - or that they would at least require an additional cycle of stability. If push comes to shove, we will postpone cryoablation for the time being. Apparently Littrup's nurse told us that they can cryoablation tumors up to 6 cm in size. The one we were thinking of doing on the left is not an emergency or urgency and we are happy with that.

Re: PF02341066 side effects, they definitely got better, but she developed some esophageal irritation in the first 4 weeks when she wasn't allowed to take the meds with food (they take pharmacokinetics)..she had some Carafate and that is all better.

The side effects are fairly tolerable, but there are wonky things with the drug. 'K' sleeps in on school days in the morning, but she is her regular self the rest of the day and evening. I still have her do a mile on the treadmill and she's still keeping up her schoolwork and wants to sing in the Spring concert.

If any of you consider this drug at some point, I'd be happy to post more. Although some were disappointed with ARQ197's effect in ASPS, it did seem to increase stability in a significant number of patients and there is a rationale that PF02341066 could be better - ARQ197 is super selective and doesn't effect the ATP binding site - but it might be too selective if there are any met receptor mutants. PF02341066 blocks at the ATP binding site and seems more effective on met receptor mutants at least in labtop experiments. But anyway. All this is theoretical. I'll let you know with the next set of scans in 2 months.