MJ on Cediranib Phase 2 clinical Trial at NCI

[Brian]

Just a quick update on MJ and the progress within the trial. She has resumed the medication after a 30 day break due to side effects already noted. She was rescanned and it was found that the tumors had increased in size 10-15 percent from the most recent scan on 12/22. So 30 days without the drug and a 10-15 percent increase in size. I guess this is the rebound that we feared. The scan did show no new growth, just an increase in the existing tumors. She has restarted the medication at 15mg and I will keep the board up to date on the progress. I feel this information is very important for all those involved with Cediranib, and also appreciate everyone sharing their experiences within this forum.

[Bonni Hess]

Dear Brian,
Your thoughtful update on MJ and the important shared information about her currrent disease status and Cediranib treatment are deeply appreciated. I am so deeply sorry about the increased tumor growth which occurred during her 30 day break from the medication, but I am very grateful that there are no new tumors, and that she is now able to resume taking the Cediranib at a reduced dosage. Did Dr. Kummar attribute the increased tumor growth to the rebound affect caused by the extended amount of time that MJ was off of the medication?
I will be holding VERY tight to Hope that the reduced dosage will prevent the elevated liver enzyme levels and concerning weight loss which MJ experienced at the higher dosage, and that resuming the medication will stabilize her disease and tumor growth, and result in more tumor shrinkage like that which she had during her first course of treatment. Please give her a hug from me and my very best wishes, and keep this Board updated as you are able.
With special caring thoughts and continued Hope,
Bonni

[Arch]

Thanks for the update Brian. Good to know that MJ is able to go back on the trial with a reduced dosage. Hopefully, her side effects will be more manageable with the reduced dose.
Rebound growth is a concern, we need to be aware of that, does anyone have any news from Paul or Clare? There were 7 people on the phase-1 trial in UK, I wonder how they are? Olga or Bonni or anyone, is there any way we can get in touch with them? Clare seemed to be stable 14 months after stopping cediranib, could it be that if we are able to take cediranib for longer, there is less of a worry with rebound growth? Any evidence like that with other anti-angiogenic agents?

[Brian]

Hello Everyone

MJ finished up two months at a reduced dosage of 15mg with scans this week. To our delight, she had positive response even at the reduced dosage, with all tumors shrinking about 10 percent over the past two months - no new growth. Some side effects, including weight loss, continue to be a concern, but we are encouraged by the results at the lower dosage. She started the trial September 2009, so onward we go!!

[Olga]

Brian - this is great, I hope it will give an insight to the clinical trial investigators in regards of the optimal dose schedule, they kind of continue to use maximum tolerated dose approach, but it is not known yet for the targeted therapies if there is a definite correlation between the maximum dose and maximum response or maximum benefit for the patient overall if consider adverse effects from drug.

[Bonni Hess]

Dear Brian,
I am so very happy to hear this wonderful and very encouraging news, and am so grateful to you for writing to share it with the Board. It is so good to know that the Cediranib seems to be effective even at the significantly reduced dosage, and as Olga said, MJ's postive results at the reduced 15 mg. dose may help to provide guidelines for the Clinical Trial investigators to better establish the best dosage for the medication while reducing the negative side effects and still maintaining the effectiveness of the drug. With the exception of MJ's continued concerning weight loss, has she experienced a reduction in the other adverse side effects including the elevated liver enzyme issue? Also, has her large primary tumor now shrunk enough to be resectable, and if so, is surgical removal of the tumor being considered by the doctors?
I am holding very tight to Hope that the Cediranib will continue to prevent new mets, to shrink/destroy the existing ones, and that MJ's weight loss will soon stabilize and she will be able to start regaining some of the lost weight. Please give MJ and yourself happy hugs from me, know how very much I am sharing and celebrating your special joy and strengthened Hope, and keep the Board updated as you are able.
With much shared happiness, special caring thoughts, and continued Hope,
Bonni

[Brian]

Bonni

All other side effects have normalized, including liver enzymes. It took a few weeks for the levels to come down, about four actually, but they have fallen within the normal range and have not increased. I don't know about resection yet of the primary, but its something we will consider probably after the next scan, with about 30 percent total reduction so far. She feels tired quite often, and continues to take medication for hypertension.

[Brian]

Hi Everyone

We had some bad news and good news today - MJ has been taken off the Cediranib trial at NCI. The weight loss was the primary reason. It has just become too much for her to stay on the trial and remain within the guidelines of the protocol.

The good news is that a new trial will be starting at NICI in Bethesda in a few months (3-6 months according to Dr Kummar) and will include Cediranib mixed with another inhibitor (not sure which one). Dr Kummar indicated they will be using this site website to recruit participation in the trial. The nurse, I am sure, will be providing more details as the trial moves forward. It is a Phase II trial.

In the meantime, we plan to have MJ take a short break, and possible take Sutent starting in August until the new trial begins.

[Olga]

Hi, I am sorry to hear that. Have you discussed the option to remove the primary in the meantime? As the primary impact of the cediranib is the blood vessels impairment, probably the surgery would be less bloody and easier?

[Fictional]

It's true that in-between clinical trials might be a good time to do surgery.

Don't know whether there is any new opinion on this, but in the past, surgeons have chosen to wait 1-6 weeks to do the surgery. If there are any tumors that might grow back quickly and be dangerous, though, it may be better to just go on Sutent and not wait. If you have to wait 3 weeks to have surgery and 3 weeks to resume a TKI, you have to have enough margin of safety being off the drug even if some rebound happens.

I think UCLA and MDAnderson may have more experience with sarcoma surgery + TKI than perhaps MSK. Memorial Sloan Kettering doesn't do as much surgery with TKIs I think.

Patrick Williams is on Cediranib + Avastin (http://caringbridge.org/visit/patrickwilliams) He also has a Facebook page. He posted that he's tolerating the combo well thus far and will have his first set of scan results later this month.

[Arch]

I'm sorry to hear this, especially since MJ's tumors were actually shrinking. I hope you will explore the possibility of primary resection during this break.
All the best.

[Bonni Hess]

Dear Brian,
I am so deeply sorry that MJ has been taken off of the Cediranib Trial due to continued weight loss despite her greatly reduced Cediranib dosage. I was so very Hopeful that the reduced medication dosage would also reduce her side effects while continuing to be effective in stabiliizing her disease and shrinking her tumors. Was MJ's continued weight loss caused by lack of appetite, nausea, and vomiting, and if so, was she given any kind of medication to try to stimulate her appetite and reduce her nausea? Was medical marijuana ever considered/offered since it is known to help with appetite and nausea issues? I am concerned about MJ staying off of a systemic treatment for very long, or waiting for the new NIH Cediranib Clinical Trial to start in 3-6 months due to the documented risk of rebound and rapid disease progression which is known to occur when anti-angiogenic TKI medications like Cediranib are discontinued. Dr.Kumar should be well aware of this risk as this is what tragically occurred when her ASPS patient Jonny Guay was abruptly taken off of his Cediranib treatment at NIH and devastatingly lost his courageous battle a couple of months later as the result of rapid disease progression. 'F' also recently shared an abstract on the Board from the June ASCO meeting which documents the loss of an ASPS patient a month after the anti-angiogenic treatment Sutent was discontinued when the patient developed disease progression after seventeen months of stability. 'F' has also cited a new study which documents successful treatment response for an ASPS patient who was treated with sequential anti=angiogenic medications, and Brittany's extremely knowledgeable Clinical Trial oncologist, Dr. Michael Sawyer, has recommended this as a treatment approach if Brittany develops resistance to her Cediranib treatment. I would be concerned about MJ waiting as long as August to start Sutent due to the risk of rebound, and strongly encourage you to discuss the rebound issue/concern with Dr. Kumar or MJ's primary oncologist. In the meantime, please give MJ a special hug from me, know that my continued most caring thoughts and best wishes are with her and your family, and keep this Board updated as you are able.
With special caring and continued Hope,
Bonni

[Fictional]

I thought of something else that could be helpful to you. When our daughter was on Sutent she was on both higher dose (37.5mg 3 weeks on / 2 weeks off or something like that) and 25 mg QD. She felt 25 mg QD was much better in terms of fatigue and appetite, and there is a rationale that it may be better than frequent on-and-off dosing (some studies say the blood vessels grow back in within 7 days, for instance). At least in renal cell CA, there was no difference in efficacy between the on/off vs. continuous, so at least some researchers recommended daily low dosing instead of intermittent cycling.

If you have any questions about Sutent, let me know. We were able to appeal to our health insurance (Blue Cross / Premera) to cover the drug...which they did. We had a higher deductible - but $200 per month sure beats $6000 per month.

[Brian]

Hello

Its been a long while since I have updated progress on MJ. She stopped the Cediranib trial in June 2010 after side effects forced her off the drug. She did have positive response to the drug for nine months. She recovered through August 2010, and then began Sutent. She went through several cycles of Sutent, through December 2010. Unfortunately, there was some disease progression on Sutent, so that has stopped as well. We are considering a clinical trial in Bethesda with EZN-2208 in combination with Bevacizumab. Its a Phase I trial at NCI in Bethesda. Anyone with input on the trial would be greatly appreciated. Thanks very much!

[Olga]

Brian, thanks for the update. I thought that it would probably make sens to move the further discussion to the MJ personal topic in the Personal Updates here http://www.cureasps.org/forum/viewforum.php?f=4
but found out that we never opened the one specific for MJ, do you want to do it now and very shortly outline the way the disease was going - when Dx, what was the situation then and what has been done between now and then. Pretty much the same you said in this your last post. Then we can add other comments there instead of doing it in the cediranib forum as it is obviously finished trial for MJ.
For a starter I would say that in the meantime she is not on the trial or any treatment I would insist of having the surgery to remove the primary, it can not be done later on if she starts the trial as Avastin (Bevacizumab) can not be taken when the surgery is done.